Gene EditingPreprint · not peer reviewedOct 20, 2026
Identification and DepMap CRISPR Dependency Analysis of a Pan-Cancer Epigenomic Signature of MYC-Driven Activation
Alsaedi MAH, Strathdee G
Research Square
Abstract While MYC is among the most frequently deregulated oncogenes in cancer, the extent to which MYC-associated gene activation is accompanied by DNA hypomethylation across diverse tumour types has remained an important, unresolved question. To address this, we integrated RNA-seq and DNA methylation data from MYC-high and MYC-low breast, liver, and colorectal tumours. Rigorously adjusting for proliferation, we…
Cell & Gene TherapyPreprint · not peer reviewedOct 20, 2026
Targeting poorly differentiated thyroid cancer with bispecific antibodies and CAR T cells from the human anti-TSHR autoantibody repertoire
Fischer C et al. (+20)
bioRxiv
Background: Poorly differentiated thyroid carcinoma (PDTC) has no effective systemic treatment option once radioactive iodine and tyrosine kinase inhibitors fail. The thyroid-stimulating hormone receptor (TSHR) is highly tissue-restricted and the anti-TSHR autoantibody repertoire of thyroid autoimmunity offers sequence-defined, fully human binders. We asked whether this repertoire can be converted into an…
Cell & Gene TherapyPreprint · not peer reviewedOct 20, 2026
Transcriptomic and phenotypic analyses reveal time-qualified patterns featuring Chimeric Antigen Receptor-T cells (CAR-T) dynamics
Murgo E et al. (+9)
Research Square
Abstract Circadian rhythms regulate immune function, yet their role in CAR-T efficacy is unclear. We profiled CD7-CAR T cells across a 24-hour time-course by RNA-sequencing and compared findings against CYCLOPS-inferred circadian phase in the independent Mullighan T-ALL cohort (n = 1,334). CD7-CAR T cells showed a reorganized circadian oscillator, with immune pathways (TNF-α, interferon-γ, IL2-STAT5) peaking in a…
Cell & Gene TherapyPreprint · not peer reviewedOct 20, 2026
Resistance of breast cancer stem cells to TROP2-targeted CAR-T therapy via the NF-κB signaling pathway
Wang H et al. (+5)
Research Square
Abstract Background Breast cancer is a prevalent female malignancy with poor treatment outcomes, and cancer stem cells (CSCs) mainly cause tumor relapse and drug resistance. This study aimed to elucidate the molecular mechanisms underlying the resistance of breast CSCs (BCSCs) to trophoblast cell surface antigen 2 (TROP2)-targeted chimeric antigen receptor T (CAR-T) therapy, with a specific focus on the regulatory…
Single-Cell & OmicsPreprint · not peer reviewedOct 20, 2026
XplainTDA: Explaining the topological structure of single-cell multi-omics data through perturbation
Giray I et al. (+3)
bioRxiv
Single-cell experiments have improved our ability to study biological systems by profiling thousands of cells simultaneously. The data can be viewed as a point cloud in a proper experimental space, whose shape is defined by the gene regulatory network. Persistent homology has been proposed as a method for studying the intrinsic structure of data and has shown the potential to reveal novel insights. Existing…
ImmunotherapyPreprint · not peer reviewedOct 20, 2026
Explore the Factors Influencing Financial Toxicity in Patients with Digestive System Cancer Receiving Immunotherapy: A Cross-sectional Study
Kuo Y et al. (+8)
Research Square
Abstract Purpose Immune checkpoint inhibitors (ICIs) are novel treatments for digestive system cancers (DSCs); however, high treatment costs and immune-related adverse events (irAEs) may contribute to financial toxicity (FT). However, the evidence regarding the association between irAEs and FT remains limited. Thus, we aimed to investigate FT and examine irAEs and other associated factors in patients with DSCs…
ImmunotherapyPreprint · not peer reviewedOct 20, 2026
Research Hotspots and Trends of Natural Killer Cells in Breast Cancer Immunotherapy: A Bibliometric Analysis
Wang Y et al. (+6)
Research Square
Abstract Objective This study employs bibliometric methods to systematically review the research landscape, evolving hotspots, and cutting-edge trends in natural killer cell-based immunotherapy for breast cancer (BC) over the past three decades (1996–2025). Methods Relevant literature was retrieved from the Web of Science Core Collection (WoSCC). CiteSpace, VOSviewer and Bibliometrix were used to analyze publication…
ImmunotherapyPreprint · not peer reviewedOct 20, 2026
Efficacy and Safety of Allergen-Specific Immunotherapy and Biologic Agents in Respiratory Allergies: A Literature Review
Moura AKA et al. (+3)
Research Square
Abstract Methods A literature review was conducted using articles published between 2014 and 2024 and indexed in the PubMed and SciELO databases to examine the efficacy and safety of allergen-specific immunotherapy and biologic medications. The findings were synthesized descriptively; no formal risk-of-bias assessment or meta-analysis was performed. Results The studies reviewed indicated that biologic agents, such…
Cancer BiologyPreprint · not peer reviewedOct 20, 2026
Antigen recognition licenses therapeutic CD8+ T cells to organize a multicellular myeloid interaction network in the tumor microenvironment
Pherez-Farah A et al. (+13)
bioRxiv
Adoptive T cell therapy (ACT) introduces activated tumor-reactive T cells into an established tumor microenvironment, yet how these therapeutic effectors communicate with the surrounding myeloid compartment remains poorly understood. Here, we combined in vivo interaction recording, single-cell profiling, and genetic perturbation of antigen presentation to resolve therapeutic CD8+ T cell-myeloid communication during…
Cancer BiologyPreprint · not peer reviewedOct 20, 2026
An Interferon-Responsive Cancer-Associated Fibroblast Subtype Shapes an Immune-Active Tumor Microenvironment and Favors Survival in Ovarian Cancer
Shi Y et al. (+6)
Research Square
Abstract Background Accumulating studies have demonstrated that discrete subsets of cancer-associated fibroblast (CAF) can potentiate antitumor immunity and are associated with favorable clinical outcomes across multiple malignancies. However, the role of CAFs within the ovarian cancer immune microenvironment remains poorly understood, and their prognostic relevance has not been fully elucidated. Methods…
Cancer BiologyPreprint · not peer reviewedOct 20, 2026
Lineage plasticity and tumor microenvironment transcriptional features define a novel aggressive state in pediatric rhabdomyosarcoma
Jachetti E et al. (+16)
Research Square
Abstract Pediatric rhabdomyosarcoma (RMS) features aberrant myogenic differentiation, pointing to lineage plasticity involvement in its development. Tumor-intrinsic regulators of epithelial-to-neuroendocrine plasticity also play roles in RMS, suggesting shared plasticity programs. Plasticity is also shaped by the tumor microenvironment; yet, mast cells (MCs), which restrain epithelial-to-neuroendocrine…
MicrobiomePreprint · not peer reviewedOct 20, 2026
Gut microbiota dysbiosis in adrenoleukodystrophy: a new piece in the puzzle?
Torreni L et al. (+16)
medRxiv
X-linked adrenoleukodystrophy (X-ALD) is the most common monogenic disorder affecting brain white matter, presenting a broad clinical spectrum from slowly progressive adrenomyeloneuropathy (AMN) to rapidly advancing cerebral demyelination. Factors influencing the variable disease expressivity remain poorly understood. We conducted shotgun metagenomic profiling of fecal samples from X-ALD patients and integrated…
MicrobiomePreprint · not peer reviewedOct 20, 2026
Persistent gut microbiota alterations after ischemic stroke are modifiable by probiotic intervention
Melton P et al. (+9)
medRxiv
The gut-brain axis has emerged as a critical modulator in neurological diseases, including stroke. While acute post-stroke dysbiosis is well established, it remains unclear whether these alterations persist long-term and can be therapeutically modulated. This study addresses this gap through integrated metagenomic and metabolomic profiling in two independent clinical stroke cohorts, complemented by experimental…
MicrobiomePreprint · not peer reviewedOct 20, 2026
Phylogenetic harmonization of cross-cohort vaginal microbiome data for machine-learning prediction of preterm birth
Park S et al. (+9)
Research Square
Abstract The vaginal microbiome is associated with preterm birth (PTB), but single-center prediction models may be limited by sample size, and public 16S rRNA datasets differ in variable regions and protocols. We integrated a Korean single-center cohort (EUMC; n = 235) with the Microbiome Preterm Birth DREAM Challenge (DC; 3,578 samples from 1,268 individuals) using phylogenetic-placement-based harmonization…
AI & Protein DesignPreprint · not peer reviewedOct 19, 2026
Proteome scale drug prioritization from AlphaFold 3 interaction confidence
Akabari R et al. (+3)
bioRxiv
AlphaFold 3 (AF3) predicts protein ligand complexes, but the utility of its confidence scores for drug prioritization remains unclear. We benchmarked AF3 interaction scores against BANDOCK+, an experimentally informed approach, using approved drugs and human protein libraries. AF3 ipTM achieved similar aggregate disease ranking performance to BANDOCK+, with differences among individual indications. These results…
Single-Cell & OmicsPreprint · not peer reviewedOct 19, 2026
Spatial transcriptomics maps region and isoform specific brain alterations in mdx and mdx 4cv models of Duchenne muscular dystrophy
Mao Q et al. (+7)
bioRxiv
Duchenne muscular dystrophy (DMD) is accompanied by cognitive and neurodevelopmental difficulties. To investigate how the loss of different dystrophin isoforms affects gene expression across brain regions, we performed spatial transcriptomics on brains from mdx and mdx 4cv mouse models (lacking Dp427 or Dp427+Dp140 respectively) and healthy controls aged 2 weeks. Both dystrophic models showed transcriptional changes…
Single-Cell & OmicsPreprint · not peer reviewedOct 19, 2026
scRBP infers cell-specific RNA-binding protein regulons from single-cell transcriptomes at gene and isoform resolution
Ma Y et al. (+14)
bioRxiv
Single-cell regulatory network inference remains dominated by transcription factors, despite RNA-binding proteins (RBPs) orchestrating major aspects of transcriptional regulation. We present scRBP, a framework that infers motif-supported RBP regulons from short- and long-read single-cell transcriptomes at gene and isoform resolution, resolves targets by transcript region (5′UTR, CDS, intron, 3′UTR), scores regulon…
Single-Cell & OmicsPreprint · not peer reviewedOct 19, 2026
scOmnom: scalable end-to-end single-cell RNA-seq analysis with auditable resolution selection
Hu IM et al. (+4)
bioRxiv
Large-scale single-cell RNA-seq analysis remains fragmented across tools, with clustering decisions and revised annotations often carried between analysis stages through custom scripts. Here, we present scOmnom, a scalable, semi-automated Python workflow connecting quality control, integration, clustering, annotation, and downstream analysis. To automate clustering-resolution selection, we developed BISC, which…
ImmunotherapyPreprint · not peer reviewedOct 19, 2026
Immune checkpoint inhibitor adverse events in colorectal cancer: a disproportionality analysis of FAERS with cross-database validation in JADER
Yan Y et al. (+7)
Research Square
Abstract Background: Colorectal cancer (CRC) background symptomatology may confound immune checkpoint inhibitor (ICI) safety signals, but no colorectal cancer-specific pharmacovigilance analysis exists. The aim was to characterize adverse-event reporting for pembrolizumab and nivolumab in CRC using the FDA Adverse Event Reporting System (FAERS) with a disease-matched comparator, and to validate the findings…
NeurotechnologyPreprint · not peer reviewedOct 19, 2026
BOWIe: Wireless Headstage for Optical Stimulation in Closed-Loop Optogenetics Experiments in Freely-moving Rodents
Silva P et al. (+7)
bioRxiv
Optogenetics is an invaluable technique in neuroscience to study brain circuits, but conventional optogenetic systems use tethered approaches to deliver light to the brain which can hinder natural behavior. Optoelectronic advances led to the development of wireless optical stimulators for optogenetics experiments, but most reported devices have low widespread use due to complex builds and reduced versatility, which…
Cancer BiologyPreprint · not peer reviewedOct 19, 2026
Functional epigenomic liquid biopsy identifies potential therapeutic vulnerabilities after enfortumab vedotin–pembrolizumab resistance in metastatic urothelial carcinoma (mUC)
Bellmunt J et al. (+17)
Research Square
Abstract Enfortumab vedotin plus pembrolizumab (EV/P) is the standard first-line treatment for advanced urothelial carcinoma (UC), yielding unprecedented clinical benefit; however, resistance ultimately develops in many patients, and longitudinal liquid biopsy offers an opportunity to monitor tumor evolution and emerging therapeutic vulnerabilities. We collected 96 serial plasma samples from 48 patients with…
MicrobiomePreprint · not peer reviewedOct 19, 2026
Integrated 16S rRNA Bioinformatics Analysis of Gut Microbiota, Predicted Pathways, and Candidate Biomarkers in Inflammatory Bowel Disease
Zehra A, Natarajan E
bioRxiv
Inflammatory bowel disease (IBD) is associated with changes in gut microbiota composition and predicted microbial functions that may relate to intestinal immune processes. This study compared gut microbiota profiles between individuals with IBD and healthy controls and examined predicted microbial pathways and their associations with bacterial genera. Publicly available 16S rRNA amplicon sequencing data from 22…
Cell & Gene TherapyOct 18, 2026
Glioblastoma immune landscape remodeling following treatment with CD70-targeted CAR-T cells.
Kourtesakis A et al. (+14)
Oncoimmunology
Chimeric antigen receptor (CAR)-T cell therapy has shown limited efficacy in glioblastoma (GB), largely because of the immunosuppressive tumor microenvironment (TME). We have previously demonstrated that the ligand-based mCD70-directed construct mCAR27 specifically eliminates CD70⁺ GB cells in vitro, and induces durable tumor remission with prolonged survival in a syngeneic model of orthotopic GB. Despite the…
Cell & Gene TherapyPreprint · not peer reviewedOct 18, 2026
A CAR T cell-amplified suppressive B cell circuit in AML
Gottschlich A et al. (+60)
bioRxiv
Immunotherapy in acute myeloid leukemia (AML) is constrained by a hostile bone marrow niche. Here we identify atypical memory B cells (Batyp) as a suppressive population within this microenvironment. Across single cell and flow cytometry cohorts, Batyp were expanded in AML, and their molecular and phenotypic profiles resembled those of atypical B cells associated with chronic inflammatory conditions. Batyp were…
NeurotechnologyPreprint · not peer reviewedOct 18, 2026
FluOpti: an open-source system for programmable whole-plate optogenetics and multi-fluorescence imaging
Nuñez I et al. (+11)
bioRxiv
Bacteria are able to self-organize into complex spatial communities, such as colonies, biofilms and swarms. Probing cells and gene networks with dynamic stimuli while preserving their spatial organization is therefore essential for understanding how bacterial communities organize across spatial and temporal scales. Optogenetics offers a powerful approach for such a task given the precise control of stimulus delivery…
Drug DiscoveryPreprint · not peer reviewedOct 18, 2026
DNA-Encoded Library-Guided Discovery of a First-in-Class Molecular Glue of the NOS1AP-SCRIB Complex in Alzheimer's Disease Patient-Derived Neurons
Kaur B et al. (+3)
bioRxiv
NOS1AP is an adaptor for neuronal nitric oxide synthase that engages several partner proteins and is implicated in Alzheimer's disease. Efforts to drug NOS1AP have sought to disrupt these; we instead report pharmacological stabilization of one interaction. Affinity selection of a 1.4-billion-member DNA-encoded library identified a benzimidazole-5-carboxamide chemotype, optimized by fragment-directed SAR to NOSTRA…
Gene EditingPreprint · not peer reviewedOct 16, 2026
Rapid RPA-CRISPR/Cas12a detection of Vibrio coralliilyticus for coral aquaculture disease surveillance
Asgari S et al. (+4)
bioRxiv
Coral aquaculture is expanding globally to support both the ornamental aquarium trade and reef-restoration initiatives, yet disease outbreaks remain a threat to production, causing potential substantial coral mortality and economic losses. Effective disease management requires early pathogen detection; however, conventional molecular diagnostics are labor-intensive and poorly suited to time-sensitive aquaculture…
Gene EditingPreprint · not peer reviewedOct 16, 2026
Base Editing as a Therapeutic Strategy for Autosomal Dominant Tubulointerstitial Kidney Disease caused by Pathogenic UMOD Variants
Diederich N et al. (+18)
bioRxiv
Autosomal dominant tubulointerstitial kidney disease caused by pathogenic UMOD variants (ADTKD-UMOD) is an untreatable monogenic kidney disease in which misfolded uromodulin is retained in the endoplasmic reticulum and exerts a toxic gain-of-function effect. Here we systematically evaluate the full spectrum of base editing strategies targeting the UMOD locus. Base editors corrected a representative missense patient…
Synthetic BiologyPreprint · not peer reviewedOct 16, 2026
Synthetic biology-guided modular engineering of the secreted cutinase FoCut5a with a carbohydrate-binding module improves poly(ester-urethane) depolymerization in Yarrowia lipolytica
Messina E et al. (+8)
bioRxiv
Poly(ester-urethane) bioconversion requires efficient polymer-degrading enzymes and microbial hosts capable of processing the resulting monomers. However, the optimal modular design of secreted cutinases for depolymerizing insoluble polyester-polyurethanes remains largely unexplored. Here, we established a combinatorial synthetic biology strategy in Yarrowia lipolytica based on the fungal cutinase FoCut5a from…
NeurotechnologyPreprint · not peer reviewedOct 16, 2026
Emergent locomotion from anatomy alone: a whole-connectome, conductance-based neuromechanical model of Caenorhabditis elegans
Li H
Research Square
Abstract Ion-channel parameters in excitable cells are strongly degenerate: many distinct conductance combinations produce the same electrical behaviour. Whether this degeneracy is a nuisance or a design principle of nervous systems cannot be decided at the single-cell level. Here we test it at the whole-animal level by coupling a conductance-based model of the complete C. elegans somatic nervous system - 292…
Drug DiscoveryPreprint · not peer reviewedOct 16, 2026
ELiAH2: update of the atlas of E3 ligases in human tissues by integrating tissue-specificity and docking properties of ligands for targeted protein degradation
Paik H, Seo S
bioRxiv
Targeted protein degradation (TPD), including proteolysis-targeting chimeras (PROTACs), requires coordinated selection of E3 ligases, target proteins, and ligands to achieve efficient and tissue-selective degradation. However, current TPD resources provide limited support for integrating tissue-specific transcriptomic evidence with structural compatibility during early candidate prioritization. Here, we present…
Gene EditingPreprint · not peer reviewedOct 15, 2026
Targeted RNA degradation of HIV-1 TAR element at 5’UTR by CRISPR-Cas13X blocks HIV-1 lytic reactivation
Lepcha TT et al. (+9)
bioRxiv
ABSTRACT Human immunodeficiency virus type 1 (HIV-1) latency remains a major barrier to a cure. Here, we developed a hypercompact CRISPR-Cas13X.1 system to target the HIV-1 5′ untranslated region (5′UTR), focusing on the transactivation response (TAR) RNA element required for Tat-dependent transcription. Following validation of a single-vector system, we screened CRISPR RNAs (crRNAs) targeting distinct 5′UTR…
Cell & Gene TherapyOct 15, 2026
Overcoming the nuclear barrier in nonviral gene therapy: mechanisms, carrier design, and translational perspectives on NLS peptide and DNA targeting sequence strategies.
Lee T et al. (+3)
Drug delivery
Efficient delivery of plasmid DNA (pDNA) into the nucleus remains a major bottleneck in nonviral gene therapy, particularly in post-mitotic and slowly dividing cells where the nuclear envelope constitutes a permanent barrier to passive entry. This review considers the two main strategies for active nuclear targeting: nuclear localisation signal (NLS) peptides, which recruit importin-α/β receptors directly to DNA…
Synthetic BiologyPreprint · not peer reviewedOct 14, 2026
Genetic circuit rewiring underlies a lineage-specific patterning machinery on butterfly wings
Tian S, Zhou JY, Mazo-Vargas A
bioRxiv
Phenotypes evolve through changes in gene regulatory networks (GRNs), but how changes in network topology contribute to phenotypic evolution is still poorly understood. Butterfly wing color patterns provide a tractable system to answer this question. Here, we compared the expression of four color pattern genes, WntA, pdm3, ivory , and Optix , in five nymphalid butterflies, and tested their regulatory connections…
NeurotechnologyPreprint · not peer reviewedOct 14, 2026
Cross-state stability and maturational similarity of the social brain connectome in children and adolescents
Lee J et al. (+4)
bioRxiv
The intra-individual stability of functional connectivity (FC) across two or more scans and the inter-individual similarity of FC patterns relative to peers capture developmental variability in functional brain organization. Despite their different referents, these measures are strongly coupled at the whole brain level; however, it remains unclear whether this relationship emerges in development, whether it extends…
Longevity & AgingPreprint · not peer reviewedOct 14, 2026
Cellular senescence changes and their association with brain structure in schizophrenia and major depressive disorder
Okada N et al. (+17)
Research Square
Abstract Individuals with schizophrenia (SZ) and major depressive disorder (MDD) may experience accelerated biological aging, potentially linked to cellular senescence and the senescence-associated secretory phenotype (SASP). While the SASP index has been reported to be elevated in MDD, its status in SZ and its relationship with brain structure remain unclear. This study investigated whether the SASP index, a…
AI & Protein DesignPreprint · not peer reviewedOct 13, 2026
PAAS reveals interpretable local structural microenvironments across proteome-scale AlphaFold models
Falcao A, Guedes R
Research Square
Abstract Protein structures are increasingly available at proteome scale, but general-purpose representations that are compact, residue-traceable and suitable for downstream analysis remain limited. We introduce Proximal Amino Acid Sets (PAAS), an unsupervised framework that converts sequence-order-independent three-dimensional residue neighbourhoods into a discrete, substitution-aware vocabulary of structural…
NeurotechnologyOct 12, 2026
Predicting IGD treatment outcomes across interventions using a whole-brain functional connectome biomarker.
Wei M et al. (+6)
Dialogues in clinical neuroscience
BackgroundAlthough treatment approaches have been explored in internet gaming disorder (IGD), however, little is known about the specific neural activity that is associated with treatment outcomes. This study aims to establish a treatment-sensitive network that reliably predicts treatment outcomes across different interventions for IGD.MethodsResting-state fMRI data were collected from 90 individuals with IGD who…
MicrobiomeOct 12, 2026
Gut microbiota shaping fatty liver disease progression.
Wysokińska M et al. (+3)
Life science alliance
The gut-liver axis is an important regulator of homeostasis, and its dysregulation has been implicated in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). In this review, we summarize current knowledge on both compositional alterations of the gut microbiome in MASLD and the functional consequences of these changes. We first discuss changes across major microbial domains…
AI & Protein DesignPreprint · not peer reviewedOct 11, 2026
CHORUS: A proteome-scale atlas of membrane interaction interfaces constructed using cross-protein language model embeddings from sequences alone
Zhao J, Huang S, Sun J
bioRxiv
Membrane proteins drive vital cellular signaling and bioenergetics yet resolving their physical interaction interfaces remains hindered by the paucity of experimental complexes and the breakdown of sequence alignments across hydrophobic bilayers. Here, we present CHORUS, a sequence-only deep-learning framework that decodes interaction sites across membrane proteins without requiring 3D structures, multiple sequence…
AI & Protein DesignPreprint · not peer reviewedOct 11, 2026
Chain of Structures: Connecting Reasoning and Generation for Protein Design
Cai Q et al. (+6)
bioRxiv
Scientific design requires reasoning in scientific spaces that represent the objects being designed. Building on Scinetics' Chain of Science Tokens, we present chain-of-structures (COS) as a concrete protein-design case study that connects reasoning and generation through explicit structural states. In this technical report, we apply COS to enzyme design, where catalytic function requires precise local geometry…
NeurotechnologyOct 8, 2026
A geometric rs-fMRI connectome descriptor reveals individual stability without robust autism group differences.
M S SP, A ST
Cognitive neurodynamics
Autism spectrum disorder (ASD) has resisted reproducible case-control characterization in resting-state functional connectivity, leaving open whether reported group differences reflect genuine biology or methodological variability. We introduce a geometric framework that represents functional connectomes on the symmetric positive-definite Riemannian manifold and quantifies individual deviation as tangent-space…
MicrobiomeOct 7, 2026
Influence of gut microbiota on chronic lymphocytic leukemia development and aggressiveness.
Frenquelli M et al. (+11)
Gut microbes reports
Chronic lymphocytic leukemia (CLL) is highly heterogeneous both clinically and biologically. Although genetic factors have been identified, several lines of evidence suggest a role for environmental factors in disease onset and progression. Diet is a recognized risk factor for various diseases, including cancer, with an established relationship to the composition of the gut microbiome. Taking advantage of the widely…
Drug DiscoveryPreprint · not peer reviewedOct 6, 2026
Chameleonicity Beyond Compactness: Conformational Persistence and Passive Permeability Across 20 PROTAC Ensembles
Jalalypour F, Mercado R
bioRxiv
Proteolysis-targeting chimeras (PROTACs) are large, flexible molecules that frequently extend beyond conventional drug-like chemical space, including Lipinski’s rule-of-five boundaries. Their membrane permeability has often been linked to molecular chameleonicity and the ability to adopt compact conformations with reduced polar surface exposure; however, the underlying conformational determinants remain unclear…
Longevity & AgingPreprint · not peer reviewedOct 5, 2026
A two-step organoid screen identifies transient p53 activation as a senolytic strategy for radiation-induced salivary gland dysfunction
Soto-Gamez A et al. (+9)
bioRxiv
ABSTRACT Radiotherapy significantly improves the survival of head and neck cancer patients. However, it frequently damages the salivary glands, causing persistent hyposalivation and xerostomia. Radiation-induced cellular senescence within the salivary gland stem/progenitor cell niche contributes to hyposalivation, suggesting that selective elimination of senescent cells could promote tissue recovery. However, the…
MicrobiomeOct 5, 2026
Gut microbiota and metabolic characteristics in PWHIV with metabolic dysfunction-associated steatotic liver disease (MASLD).
Liu H et al. (+6)
Virulence
The global prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among persons with HIV (PWHIV) is estimated at 34%. This study examined the influence of gut microbial and metabolic alterations in PWHIV with MASLD. We conducted 16S rRNA sequencing on 60 fecal samples (24 from HIV group and 36 from HIV-MASLD group) to assess microbial composition, and employed LC/MS-based metabolomics on both…
MicrobiomeOct 4, 2026
Localized co-inoculation of compatible Bacillus subtilis and Trichoderma afroharzianum is associated with shifts in the root microbiome and improves plant performance in sorghum.
Pant B, Khan M, Kabir AH
Microbiological research
Although bacterial-fungal consortia have been investigated for plant growth promotion, their effects on sorghum performance and associated root microbial taxa remain less characterized. Here, we investigated how individual and combined inoculation with Bacillus subtilis and Trichoderma afroharzianum influenced sorghum performance and root microbiome assembly. The in vitro co-culture assay demonstrated the…
mRNA & VaccinesOct 2, 2026
Cross-clade protection against human H5N1 isolates by a clade 2.3.4.4b HA mRNA vaccine in mice.
Shichinohe S et al. (+9)
Vaccine
The recent spread of clade 2.3.4.4b H5N1 high pathogenicity avian influenza (HPAI) viruses into mammals, despite limited human infections to date, has raised serious public health concerns and highlights the need for rapidly deployable vaccines, such as mRNA-based platforms, to strengthen pandemic preparedness. Here, we evaluated the effectiveness of an mRNA vaccine encoding the HA of NIID-002, a WHO-recommended H5…
MicrobiomeOct 2, 2026
Root exudate-mediated interspecific interactions reshape the rhizosphere microbiome and promote the accumulation of bioactive compounds in Pinellia ternata.
Gu QY et al. (+8)
Microbiological research
Plant recognition and responses to neighbors are key mechanisms that regulate interspecific interactions. Although aboveground signaling via volatile organic compounds has received increasing attention, the role of soil-derived signals in belowground interactions remains poorly understood. In this study, a peanut (Arachis hypogaea L.)-Pinellia ternata (Thunb.) Makino intercropping system was used to investigate how…
Drug DiscoveryPreprint · not peer reviewedOct 2, 2026
Engineered CTLA-4 targeting chimeras for targeted protein degradation and immune synapse reprogramming
Ren P et al. (+12)
bioRxiv
Despite the success of immune checkpoint blockade in cancer therapy, overcoming the immunosuppressive tumor microenvironment remains a major barrier to durable responses. Here, we introduce cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)-targeting chimeras (cTACs), a class of synthetic molecules that harness CTLA-4-mediated trans-endocytosis (TE) for targeted protein degradation across cellular boundaries. The…
Longevity & AgingPreprint · not peer reviewedOct 1, 2026
Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence
Simpson DJ et al. (+13)
medRxiv
Cellular senescence is a central hallmark of aging, yet its measurement in humans remains invasive, low-throughput and tissue-specific, precluding population-scale study. We developed Methylation-associated Gene Expression (MaGE) predictors: whole-blood DNA methylation proxies of p14 ARF , p16 INK4A and p21 CIP1 expression, plus a composite score, providing the first scalable measure of senescence-marker expression…
NeurotechnologySep 30, 2026
A spatial-channel reconstruction guided frequency-time-space deep neural framework for SSVEP-based brain-computer interface EEG decoding.
Wu X et al. (+8)
Cognitive neurodynamics
In recent years, steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) have attracted extensive attention owing to their high information transfer rate (ITR) and multi-target recognition capability. Deep learning (DL) methods have shown strong potential in SSVEP feature extraction and target frequency classification. However, their relatively high model complexity and dependence on…
Cancer BiologySep 29, 2026
Binding mechanism of the molecular glue inhibitor in overcoming the "undruggable" Kirsten rat sarcoma viral oncogene homolog through conformational remodeling.
Liang H et al. (+7)
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
Kirsten rat sarcoma viral oncogene homolog (KRAS) protein, a member of prevalent oncogenic driver, is difficult to be targeted and inhibited by traditional inhibitors due to its complex binding surface and mutation-prone property. Molecular glue inhibitor RMC-7977 is designed to break through the undruggable property of KRAS, it bridges KRAS and cyclophilin A (CYPA) to inhibit KRAS. However, RMC-7977's molecular…
Synthetic BiologyPreprint · not peer reviewedSep 28, 2026
Next-gen glycoengineering: combining cellular and metabolic engineering to fine-tune mAb β1,4-galactosylation
Tsopanoglou A et al. (+7)
bioRxiv
N-linked Fc galactosylation drives variability in therapeutic mAb quality, affecting complement-dependent cytotoxicity and ADCC. Current control strategies suffer from narrow ranges, productivity loss, or unwanted glycoforms. Here, we combine metabolic and cellular glycoengineering by feeding 2-deoxy-2-fluorogalactose (2FG) to CHO cells engineered for hypergalactosylation via COSMC knockout and…
mRNA & VaccinesPreprint · not peer reviewedSep 28, 2026
Evaluating a Potential Dose-Sparing Self-Amplifying RNA Vaccine for Induction of Functional Antibodies to Blood-Stage Plasmodium falciparum Malaria
Thomas A et al. (+6)
Preprints.org
Introduction: Next-generation malaria vaccines are urgently needed to provide greater efficacy and longevity. Antibodies targeting blood-stage merozoites can confer protection against clinical malaria through multiple Fc-mediated functions. In particular, merozoite surface protein 2 (PfMSP2), is a known target of protective antibodies that can clear merozoites via multiple antibody Fc-mediated functions, making is a…
Longevity & AgingOpen accessSep 25, 2026
[Corrigendum] Adjudin delays cellular senescence through Sirt3‑mediated attenuation of ROS production.
Geng K et al. (+3)
International journal of molecular medicine
Following the publication of the above article, a concerned reader drew to the authors' attention that, regarding the images of the mouse embryo fibroblast (MEF) cells with senescence‑associated β‑galactosidase (SA‑β‑gal) staining shown in Fig. 1B on p. 3254, the panels on the far left and the far right on the bottom row of data [showing treatments with 0 µM and 40 µM adjudin respectively in the presence of…
Cell & Gene TherapySep 24, 2026
Anti-PD-L1 scFv-secreting fifth-generation GD2-CAR T cells enhance antitumor function against GD2-low retinoblastoma.
Yuti P et al. (+8)
Molecular therapy. Nucleic acids
Retinoblastoma (RB) is an aggressive pediatric intraocular malignancy in which chemoresistant or relapsed disease often requires enucleation, leading to vision loss. GD2-targeted chimeric antigen receptor (CAR) T cells are promising for GD2-positive tumors, but PD-L1-mediated immunosuppression and reduced surface antigen density can limit their activity. We developed a fifth-generation anti-GD2 CAR (GD2-CAR5)…
Synthetic BiologyPreprint · not peer reviewedSep 24, 2026
Metabolic engineering of Salmonella enterica for coupled kynurenine sensing and depletion enhances antitumor efficacy
Varsha KK et al. (+13)
bioRxiv
Immunosuppressive tumor metabolic microenvironment remains a major barrier to effective cancer therapy. Tumor-targeting Salmonella enterica strains were engineered to deplete the intratumoral immunosuppressive kynurenine, triggering metabolic rewiring and fostering an active antitumor immune microenvironment. Equipping S. enterica VNP20009 with bacterial kynureninase enzyme (KynU) and a kynurenine transporter…
Cell & Gene TherapyOpen accessSep 23, 2026
Preclinical evaluation of SLC35D3-targeted CAR-T cells for tumor-selective immunotherapy.
Someya S et al. (+5)
Biochemistry and biophysics reports
Chimeric antigen receptor (CAR)-T therapy has transformed management of hematological malignancies, yet efficacy in solid tumors is limited by scarcity of tumor-restricted antigens. Here we characterize SLC35D3, a nucleotide-sugar transporter that we previously identified through integrated transcriptomic and protein-level analyses, as a novel therapeutic target and provide the first preclinical evaluation of…
Longevity & AgingPreprint · not peer reviewedSep 23, 2026
Peroxisomal Import Stress Drives Cellular Senescence through SCAF1-dependent Suppression of Mitoribosome Biogenesis
Correia J et al. (+3)
bioRxiv
Communication between peroxisomes and mitochondria is essential for cellular metabolic homeostasis, yet how peroxisomal import stress impacts mitochondria function during aging and cellular senescence remains poorly defined. Using a genome-wide CRISPR screening in HEK293 cells under peroxisome import stress, we identified SCAF1 (SR-related CTD-associated factor 1) a known canonical nuclear pre-mRNA splicing factor…
Cancer BiologySep 23, 2026
A triple-immunomodulatory quercetin nanoplatform to reinforce T-cell function and remodel tumor microenvironment.
Chen Y et al. (+6)
Biomaterials advances
Immune checkpoint inhibitors (ICIs) often exhibit limited clinical efficacy due to insufficient infiltration of T cells in the tumor microenvironment (TME). To address this challenge, we utilized quercetin, an active ingredient of traditional Chinese medicine, as an alternative ICI, and developed a hyaluronic acid-coated manganese-embedded mesoporous silica nanoparticle (HA-MSN(Mn) for TME-triggered co-delivery…
Single-Cell & OmicsSep 22, 2026
Intelligent programmable droplet with deterministic cell control for quantitative single-cell metabolic analysis.
Yu Z et al. (+18)
Biosensors & bioelectronics
Single-cell metabolic heterogeneity influences cell state, disease progression, and therapeutic response, yet quantitative metabolic analysis remains constrained by stochastic cell loading and uncertain droplet occupancy. Here, we developed an intelligent programmable droplet microfluidic platform (ProgDrop-Met) that integrates dielectrophoresis (DEP)-assisted cell encapsulation, deep-learning (DL)- assisted…
Synthetic BiologySep 22, 2026
Systems metabolic engineering of a plasmid-free <i>Escherichia coli</i> cell factory for high-level cytidine production.
Zhao R et al. (+12)
Synthetic and systems biotechnology
Cytidine is an important precursor for nucleoside pharmaceuticals, but its fermentative production is constrained by competing degradation, poor selectivity of pyrimidine flux, insufficient precursor supply, and energy-redox imbalance. In this study, a plasmid-free E. coli cell factory was constructed through systems metabolic engineering. Sequential deletion of cytidine degradation, salvage, and precursor-consuming…
Single-Cell & OmicsSep 21, 2026
Single-cell DNA methylation profiling reveals epigenetic signatures associated with in vitro maturation of bovine oocytes and conserved patterns with porcine oocytes.
Abril-Parreño L et al. (+5)
Theriogenology
In vitro maturation (IVM) of oocytes is a key step in bovine in vitro embryo production, but concerns remain regarding its potential effects on oocyte competence and epigenetic regulation. Information on the DNA methylation profile of bovine oocytes matured in vitro is still limited and inconsistent. In this study, we applied single-cell DNA methylation sequencing to characterise methylation patterns associated with…
Synthetic BiologySep 21, 2026
Branched-chain amino acid biosynthetic platforms in prokaryotic cell factories: metabolic engineering and value-added chemical biomanufacturing.
Lai R et al. (+5)
Biotechnology advances
Branched-chain amino acids (BCAAs) are recognized not only as industrially important fermentation products but also as versatile biosynthetic platforms for the production of branched-chain value-added chemicals. The characteristic branched carbon skeletons of BCAAs, together with their metabolically versatile intermediates, enable the biosynthesis of a broad spectrum of value-added chemicals, including…
NeurotechnologySep 21, 2026
Altered Kullback-Leibler similarity gradients in cocaine use disorder: Connectome constraints and multiscale biological contextualization.
Wang R et al. (+5)
Journal of affective disorders
BackgroundCortical morphological alterations are evident in cocaine use disorder (CUD), yet their organization within macroscale cortical hierarchies, relationship to structural connectome architecture, and associations with multiscale biological reference maps remain incompletely understood.MethodsUsing structural MRI from 71 CUD patients and 60 healthy controls, we constructed individual-level morphological…
NeurotechnologySep 21, 2026
A novel motor imagery brain-computer interface classification framework based on augmented covariance matrix: deep Riemannian geometry learning with self-attention mechanism.
Yan T et al. (+9)
Cognitive neurodynamics
The rapid development of motor imagery brain-computer interface (MI-BCI) technology has introduced a novel mode of human-machine interaction, drawing significant interest. However, due to the nonlinearity and nonstationarity of motor imagery signals, this communication method faces challenges such as low recognition accuracy and poor stability, which severely hinder the practical application of MI-BCIs. Riemannian…
Longevity & AgingOpen accessSep 21, 2026
GMPS drives pancreatic cancer progression via suppressing DNA damage, STING activation and cellular senescence.
Li Y et al. (+10)
Translational oncology
BackgroundPancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy with scarce viable treatment targets. Metabolic rewiring is a typical characteristic of PDAC, but the roles of many metabolic enzymes remain poorly defined.MethodsWe integrated DepMap and TCGA data to screen metabolic genes essential for PDAC proliferation and poor prognosis. Expression patterns were validated by…
MicrobiomeSep 19, 2026
Next-generation fermented foods from non-conventional proteins: Linking fermentation dynamics, flavor chemistry, and gut microbiome modulation.
Zhao J et al. (+13)
International journal of food microbiology
The urgent need to diversify protein sources beyond animal agriculture has propelled non-conventional proteins (e.g., insects, microalgae, single-cell organisms, novel plants) to the forefront of food innovation. However, their adoption is limited by off-flavors, anti-nutritional factors, and low digestibility. Fermentation can address these drawbacks and may impart health-relevant benefits, though human evidence…
Drug DiscoverySep 19, 2026
Design, synthesis and biological evaluation of a series of new, potent FLT3 PROTAC degraders with rigid linkers.
Zhou L et al. (+13)
Bioorganic & medicinal chemistry
Fms-like tyrosine kinase 3 (FLT3), a member of the type III receptor tyrosine kinase family, is identified as a promising drug target for treatment of acute myeloid leukemia (AML). Here, we designed and synthesized a series of new FLT3 PROTAC degraders by incorporating rigid linkers between gilteritinib and CRBN ligand. Among them, ZLC6-49 and ZLC10-3 were identified as the most potent degraders with DC50 values of…
mRNA & VaccinesPreprint · not peer reviewedSep 18, 2026
Single-cell sequencing-based elucidation of the molecular mechanisms by which the COVID-19 mRNA vaccine remodels the tumor microenvironment and sensitizes immune checkpoint inhibitors via the IFN-I pathway
Hong S, Yan W
Research Square
Abstract COVID‑19 mRNA vaccines activate the type I interferon (IFN‑I) pathway and exert anti‑tumor immunomodulatory effects, yet the mechanisms underlying tumor microenvironment (TME) remodeling and immune checkpoint inhibitor (ICI) sensitization remain poorly defined. Public single‑cell, bulk and multi‑omics datasets were integrated with Seurat, CellChat and WGCNA to characterize post‑vaccination IFN‑I activation…
MicrobiomeSep 18, 2026
Gut microbiota, metabolome and hormone profiles associate with pregnancy-related biomarkers in sheep with frozen embryo transfer.
Chen L et al. (+12)
Theriogenology
Recipients' gut microbiota and serum metabolites are linked to pregnancy outcomes in frozen embryo transfer (FET), but the underlying integrative mechanisms remain unclear. Here we compared the gut microbiome, serum metabolome, and reproductive hormones between pregnant (P group) and non-pregnant (N group) Small-Tailed Han ewes at three time points: prior to oestrus detection (1st), prior to embryo transfer (2nd)…
ImmunotherapySep 17, 2026
An endoplasmic reticulum-enriched nanogel couples ferroptotic tumor damage with macrophage reprogramming for triple-negative breast cancer immunotherapy.
Chen H et al. (+9)
Bioactive materials
Triple-negative breast cancer (TNBC) is characterized by severely immunosuppressive tumor microenvironment (TME), which leads to tumor ferroptosis resistance and dominant protumor M2 macrophages, restraining innate-to-adaptive antitumor immune cascade. Herein, an endoplasmic reticulum (ER)-enriched pH/redox-sensitive SPIONS@P-CpG-DOX nanogel was constructed to realize dual ER-targeted manipulation on TNBC cells and…
ImmunotherapyOpen accessSep 16, 2026
A bladder microenvironment-adaptive ceria nanozyme hydrogel enables urea-responsive intravesical chemo-immunotherapy.
Yuan Y et al. (+9)
Bioactive materials
Bladder cancer intravesical therapy remains limited by rapid urinary washout, insufficient penetration across the bladder mucosal barrier, and an immunosuppressive tumor microenvironment. Here, we developed a bladder microenvironment-adaptive chemo-immunotherapy system, Gel/UCeNZ/Gem/CpG, to improve local bladder cancer treatment. In this system, urease-modified CeO2 nanozymes (UCeNZ), gemcitabine (Gem), and CpG…
Drug DiscoverySep 15, 2026
Development and validation of an LC-MS/MS method for the novel PROTAC KT-474 in rat and mouse plasma: Application to dose-dependent pharmacokinetics and metabolite identification in mice.
Oh JH, Vo DK, Maeng HJ
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
KT-474 is a novel orally bioavailable proteolysis-targeting chimera (PROTAC) that selectively degrades interleukin-1 receptor-associated kinase 4 (IRAK4) and is currently in phase 2 clinical trials for inflammatory diseases. In this study, we developed and validated a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of KT-474 in rat and mouse plasma and successfully…
Cancer BiologySep 14, 2026
Stepwise progressive dual-regulated micelles enhance the therapeutic efficacy of hepatocellular carcinoma by remodeling the tumor microenvironment.
Chen M et al. (+8)
Biomaterials advances
ObjectiveHepatocellular carcinoma (HCC) is a highly malignant tumor characterized by severely immunosuppressive tumor microenvironment (TME), high recurrence and metastasis, and unsatisfactory clinical outcomes. Tenacissoside H (Ten H) shows remarkable anti-HCC activity, while ginsenoside Rh2 (GRh2) effectively regulates TME and reverses immunosuppression. However, their poor water solubility, low in vivo…
AI & Protein DesignSep 11, 2026
Systematic benchmarking of AlphaFold and SWISS-MODEL kinase structures for structure-based drug discovery.
Bahena-Culhuac E, Bello M
Journal of molecular graphics & modelling
Accurate protein structure prediction is fundamental to structure-based drug discovery. However, the practical performance of deep learning-based models such as AlphaFold compared with traditional homology modeling approaches like SWISS-MODEL remains incompletely evaluated in realistic drug-design workflows. Here, we systematically benchmark AlphaFold2 and SWISS-MODEL using a curated dataset of 20 kinase structures…
Longevity & AgingOpen accessSep 11, 2026
A breast tissue-specific epigenetic clock provides accurate chronological age predictions and reveals de-correlation of age and DNA methylation in tumor-adjacent and tumor samples.
Garma LD et al. (+17)
Epigenetics
Epigenetic clocks have been widely used to estimate biological age across various tissues, but their accuracy in breast tissue remains suboptimal. Classical models such as Horvath's and Hannum's clocks perform poorly in predicting chronological age in breast tissue, underscoring the need for a tissue-specific approach. In this study, we introduce a Breast Tissue-specific Epigenetic Clock (BTEC), developed using DNA…
Synthetic BiologySep 10, 2026
Multidimensional metabolic engineering strategies for efficient production of branched-chain amino acids and their derivatives in Escherichia coli and Corynebacterium glutamicum.
Zhao G et al. (+5)
Biotechnology advances
Branched-chain amino acids (BCAAs), comprising L-valine, L-leucine, and L-isoleucine, are essential amino acids with extensive applications in food, feed, pharmaceuticals, and cosmetics. Escherichia coli and Corynebacterium glutamicum, the two predominant industrial workhorses have been extensively engineered for high-level BCAAs biosynthesis. This review presents a comprehensive analysis of recent advances in…
Drug DiscoveryOpen accessSep 10, 2026
From prediction to performance: <i>In silico</i>-supported formulation of amorphous solid dispersions for PROTAC NX-2127.
Stakemeier A et al. (+7)
International journal of pharmaceutics: X
The oral delivery of PROTACs is frequently limited by poor aqueous solubility and low membrane permeability, whereas early formulation development is often constrained by limited drug substance availability. To address these challenges, this study established a material-sparing workflow integrating in silico prediction with in vitro screening to efficiently support formulation development of the model PROTAC…
Cell & Gene TherapySep 8, 2026
Clinical immunogenicity in rAAV gene therapy: Insights and implications.
Gulve N et al. (+6)
Molecular therapy. Advances
Recombinant adeno-associated viruses (rAAV) provide prolonged therapeutic protein expression in multiple target organs after single administration, delivering significant clinical benefits with a well-characterized safety profile, and can be further supported by active immune management strategies. Systemic rAAV gene therapy is associated primarily with transient hepatocellular injury, while complement-mediated…
Longevity & AgingSep 8, 2026
Cellular senescence as endocrine information failure in aging.
Bi Z, Lin Y
Ageing research reviews
Endocrine organs translate nutrient, stress and circadian cues into hormone outputs that coordinate whole-body physiology. Cellular senescence can distort this communication by changing endocrine-cell identity, stimulus-secretion coupling, secretory timing and local immune or paracrine signaling. Evidence is strongest in pancreatic β-cells and the adrenal zona fasciculata, where composite senescence phenotypes have…
Single-Cell & OmicsSep 7, 2026
Single-cell Raman spectroscopy combined with deep learning for antimicrobial resistance detection in Mycobacterium abscessus.
Li J et al. (+5)
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
Mycobacterium abscessus (M. abscessus) is a rapidly growing nontuberculous mycobacterium that poses a serious therapeutic challenge due to its intrinsic and acquired resistance to multiple antibiotics. Conventional antimicrobial susceptibility testing (AST) is slow and labor-intensive, underscoring the urgent need for rapid, culture-free alternatives. Here, we present a phenotype-based approach that integrates…
Cancer BiologySep 6, 2026
Manganese-doped zinc oxide Nano-agonists activating the cGAS-STING pathway to potentiate anti-tumor immunotherapy and reprogram the immunosuppressive tumor microenvironment.
Hou Z et al. (+4)
Biomaterials advances
The cyclic GMP-AMP synthase - stimulator of interferon genes (cGAS-STING) innate immune pathway is an intriguing, but still challenging, target for cancer immunotherapy. The current small molecule STING agonists have several limitations, such as low membrane permeability, rapid enzymatic degradation, lack of tumor accumulation and dose-limiting systemic toxicity. In this work, we report the design and synthesis of…
Cell & Gene TherapySep 4, 2026
Management of acute infusion-related reactions in AAV gene therapy guided by mechanistic insight.
Sullivan BA et al. (+10)
Molecular therapy. Advances
Infusion-related reactions (IRRs), serious immune events that occur either during or within six hours of an infusion, can occur with adeno-associated virus (AAV) gene therapy. IRRs may be attributed to IgE-mediated hypersensitivity, leading to treatment discontinuation due to concern about progressive, life-threatening allergic reactions. IRRs were observed in two participants who received an AAV8 gene therapy…
Gene EditingSep 3, 2026
Paper microfluidic LAMP-CRISPR/enAsCas12a platform for multiplex detection of waterborne pathogens in drinking water.
Du W et al. (+11)
Talanta
Pathogenic contamination poses a threat to drinking water safety and public health. To address contamination by Escherichia coli (E. coli), Salmonella spp., and Shigella spp., this study developed paper microfluidics for on-site multi-target detection based on an integrated LAMP-CRISPR/enAsCas12a assay. The device integrates nucleic acid enrichment, purification, elution, and multi-channel reaction processes into a…
Gene EditingSep 3, 2026
A single-tube dual-channel CRISPR platform for genotyping of waterfowl reoviruses.
Zhang J et al. (+9)
Talanta
Waterfowl reovirus (WRVs) includes two genotypes, Genotype I (Muscovy duck reovirus, MDRV) and Genotype II (novel duck reovirus, NDRV). They have the same clinical manifestations, but different pathogenicity, and can co-infect individual hosts, resulting in diagnostic ambiguity that cannot be solved by single-target detection. Here, we report a single-tube dual-channel platform coupling recombinase polymerase…
mRNA & VaccinesPreprint · not peer reviewedSep 2, 2026
Computationally Guided Design of TANSR-Vax: An Integrated Self-Amplifying RNA–Lipid Nanoparticle Strategy for Overcoming Immune Exclusion and Stromal Suppression in Hepatocellular Carcinoma
Kassab M
Research Square
Abstract Background: Hepatocellular carcinoma (HCC) develops within a highly tolerogenic hepatic environment characterized by impaired antitumor T-cell activity, immunosuppressive signaling, stromal restriction, and accumulation of suppressive myeloid and regulatory lymphocyte populations. Although immune checkpoint inhibitors and molecularly targeted combinations have improved the systemic treatment of advanced…
Gene EditingSep 1, 2026
Rapid on-site and simultaneous detection of four foodborne Vibrio species in seafood using a microfluidic RPA-CRISPR/Cas12a platform.
Chen W et al. (+10)
Talanta
Foodborne Vibrio species commonly contaminate seafood and often co-occur, complicating rapid on-site detection. We developed a centrifugal microfluidic chip integrating one-pot RPA-CRISPR/Cas12a for simultaneous detection of four key species: V. parahaemolyticus, V. vulnificus, V. cholerae, and V. alginolyticus. In this system, target-specific RPA amplification generates amplicons that activate Cas12a-mediated…
Drug DiscoverySep 1, 2026
Discovery and characterization of PGC-01: An effective GSDMD-targeting PROTAC.
Wang QQ et al. (+12)
European journal of medicinal chemistry
As the key executioner protein of pyroptosis, GSDMD represents a promising yet underexplored therapeutic target for inflammatory diseases. In this study, we explored a PROTAC-based degradation approach targeting GSDMD for the treatment of pyroptosis-driven inflammatory conditions. Through screening of our in-house compound library, we identified a high-affinity GSDMD binder, PGC (KD = 9.42 nM). Through rational…
ImmunotherapyAug 31, 2026
Self-sustaining ROS-responsive hydrogel enabled delivery of PROTAC/Ce6 nanoparticles via PDT-Epigenetic protein degradation to amplify pyroptosis for enhanced cancer immunotherapy.
Gong L et al. (+10)
Biomaterials
Cancer immunotherapy exhibits limited efficacy in immunologically "cold" tumors due to insufficient T-cell infiltration and immunosuppressive tumor microenvironment. The efficacy of photodynamic therapy (PDT) is restricted by inadequate tumor-specific aggregation of photosensitizers and therapeutic resistance regulated by epigenetics. Herein, we engineered a light-driven, ROS-responsive hydrogel (PACL@Gel) for…
mRNA & VaccinesAug 31, 2026
Protease-shielded PRG4 self-amplifying RNA lipid nanoparticles restore cartilage homeostasis in osteoarthritis.
Zhang Z et al. (+9)
Biomaterials
Osteoarthritis (OA) is a debilitating joint disease characterized by progressive loss of boundary lubrication and disruption of cartilage homeostasis. Proteoglycan 4 (PRG4) is a critical boundary lubricant, but PRG4 function in OA may be compromised by reduced local expression, intra-articular clearance and protease-mediated processing within the inflamed joint microenvironment. Here we identified conserved…
Single-Cell & OmicsAug 29, 2026
Pan-cancer single-cell atlas of immunotherapy response identifies ZNF385A as a regulator of immune evasion in small cell lung cancer.
Hou J et al. (+8)
Biochimica et biophysica acta. Molecular basis of disease
Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of solid tumors, response rates in patients with small cell lung cancer (SCLC) remain limited, and acquired resistance is highly prevalent. The underlying mechanisms of this immunotherapy resistance remain to be fully elucidated. Clinically, SCLC typically manifests as an "immune-cold" tumor, characterized by a low abundance of…
ImmunotherapyAug 26, 2026
Balancing speed and separation: A high-throughput native mass spectrometry platform for screening complex bispecific antibody variants.
Spitler K et al. (+8)
Talanta
High-throughput liquid chromatography coupled to mass spectrometry (LC-MS) workflows are increasingly required to support the structural characterization of complex antibody formats such as multispecific (e.g. 2 + 1 and 1 + 1+1) and bispecific antibodies (bsAb) where misassembled product related variants pose significant challenges to analytical process development and patient safety. Conventional size-exclusion…
NeurotechnologyAug 26, 2026
Associations between human oxytocin receptor gene promoter DNA methylation and brain structural connectome in panic disorder in Korea.
Kim HJ et al. (+4)
Journal of affective disorders
AimsEpigenetic regulation of the oxytocin receptor gene (OXTR), particularly DNA methylation (DNAm), has been linked to insecure attachment, anxiety-related phenotypes, and suicidality. However, its role in panic disorder (PD) and brain network dysfunction remains unclear. This study examined whether peripheral OXTR DNAm and OXTR DNAm-associated structural connectivity are related to clinical symptoms of…
Single-Cell & OmicsAug 25, 2026
Single-cell transcriptomic-driven design of cascade-responsive hydrogel with bioinspired nanocellular pacemaker for aged bone regeneration.
Gu HY et al. (+9)
Biomaterials
Age-related bone defects remain poorly repaired due to a vicious cycle involving senescent bone marrow mesenchymal stem cells (BMSCs) and pro-inflammatory macrophages. We unveil circadian disruption as the underlying driver via single-cell transcriptomics and propose an "internal clock-repairing, external immunity-reprogramming" strategy. Inspired by cardiac pacemakers that sense signals and rectify rhythms, we…
Synthetic BiologyOpen accessAug 25, 2026
Engineered bacterial therapeutics from synthetic biology to clinical translation: A multi-database scientometric analysis, 2000-2026.
Zhou H et al. (+5)
Human vaccines & immunotherapeutics
Engineered bacterial therapeutics integrate programmable strain engineering with biomedical functions such as sensing, delivery, immune modulation, microbiome intervention, and disease management. This study conducted a multi-database bibliometric analysis to map the knowledge structure, collaboration patterns, and translational direction of this field. Bibliographic records were retrieved from Web of Science Core…
Gene EditingOpen accessAug 24, 2026
Strategy for enhanced production of A40926B0 in <i>Nonomuraea gerenzanensis</i> using an efficient CRISPR/AsCas12f1 system.
Wang X et al. (+8)
Synthetic and systems biotechnology
The global emergence of vancomycin-resistant Gram-positive pathogens underscores the urgent need for efficient production of novel lipoglycopeptide antibiotics. Dalbavancin, a last-resort therapeutic agent, relies on its key biosynthetic precursor A40926B0, whose industrial manufacture is severely limited by the low yield of wild-type Nonomuraea gerenzanensis and inefficient genetic tools for this rare actinomycete…
Gene EditingAug 24, 2026
Bivalent aptamer-assisted CRISPR-Cas12a sensor for precise vancomycin therapeutic drug monitoring.
Lv L et al. (+4)
Talanta
Therapeutic drug monitoring (TDM) of vancomycin (VAN) is critical for maximizing efficacy and minimizing toxicity, but conventional methods are constrained by high costs, slow turnaround times, and operational complexity. To address these limitations, we developed a novel Bivalent Aptamer-assisted CRISPR-Cas12a Sensor (termed BACS) for rapid and precise VAN detection. Central to this platform is a high-affinity…
Cell & Gene TherapyOpen accessAug 20, 2026
A dual-targeting mRNA lipid nanoparticle restores ABCA1-dependent cholesterol homeostasis to promote repair of age-related bone defects.
Cheng M et al. (+17)
Bioactive materials
Cholesterol regulates autophagy and aging, yet its role in bone marrow mesenchymal stem cell (BMSC) senescence remains unclear. We demonstrate that ABCA1 palmitoylation is associated with its lysosomal localization and lysosome-associated cholesterol transport, thereby contributing to autophagy inhibition, senescence, and impaired osteogenesis. However, directly perturbing ABCA1 palmitoylation impaired cholesterol…
AI & Protein DesignOpen accessAug 20, 2026
AlphaFold 3 prediction of TCR mimic Fv - pMHC complex structures and their validation and optimization.
Sarkar A et al. (+3)
mAbs
Monoclonal antibody-derived chimeric antigen receptors (CAR) that mimic T‑cell receptors (TCR) on binding to peptide-major histocompatibility complex (pMHC) and activating T‑cell functions hold great promise for the development of effective immunotherapy. This study applied AlphaFold 3 (AF3) to model the quaternary structures of TCR mimic antibody variable fragment (TCRm Fv) complexed with…
Cancer BiologyAug 20, 2026
Digital droplet PCR and liquid biopsy in acute myeloid Leukemia: bridging translational research and clinical practice.
El-Sehrawy AAMA et al. (+9)
Clinica chimica acta; international journal of clinical chemistry
Acute myeloid leukemia (AML) is a genetically heterogeneous and dynamically evolving malignancy in which morphologic remission does not necessarily indicate eradication of disease. Bone marrow examination remains central to diagnosis and response assessment, yet repeated aspiration is invasive, may be affected by hemodilution and spatial sampling, and provides only intermittent snapshots of an evolving clonal…
Synthetic BiologyOpen accessAug 19, 2026
Combinatorial metabolic engineering of <i>Mycobacterium neoaurum</i> LY-2 for efficient androstenedione production from phytosterols.
Xu L et al. (+6)
Synthetic and systems biotechnology
Androstenedione (AD) is an important precursor for the synthesis of corticosteroids, sex hormones, and other high-value steroid pharmaceuticals. Microbial conversion of phytosterols provides a sustainable route for AD production, but current production levels remain insufficient for practical industrial application. In this study, a modular metabolic engineering strategy was developed to improve AD biosynthesis from…
Gene EditingAug 18, 2026
A smartphone-assisted one-tube ERA-CRISPR/Cas12a biosensor for integrated detection of hypervirulence and antimicrobial resistance determinants in Klebsiella pneumoniae.
Xu L et al. (+6)
Talanta
The global emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains co-harboring critical antimicrobial resistance determinants pose a serious threat to public health and clinical management. Rapid identification of virulence- and resistance-associated genes is therefore essential for early diagnosis, antimicrobial stewardship, and infection control. In this study, we developed a smartphone-assisted one-tube…
ImmunotherapyAug 18, 2026
Peptide-functionalized magnetic nanobeads for EpCAM-targeted CTC isolation and immunotherapy efficacy evaluation in liver cancer.
Li X et al. (+10)
Talanta
Primary liver cancer lacks robust biomarkers for anti-PD-1/PD-L1 therapy. Methods: We engineered peptide-functionalized magnetic nanobeads (Pep@MNPs) for high-efficiency, EpCAM-dependent capture of circulating tumor cells (CTCs). This nanotechnology-based platform enabled a precise fluorescence quantitative system (cTPS) associate with immunotherapy outcomes in hepatocellular carcinoma and intrahepatic…
ImmunotherapyAug 18, 2026
Paving the way for immunotherapy: Simvastatin-primed dual-targeting NPTAC overcomes immune resistance in hepatocellular carcinoma.
Chen C et al. (+11)
Biomaterials
Immune checkpoint blockade (ICB)-based regimens, tyrosine kinase inhibitors, and transcatheter arterial chemoembolization (TACE) are major clinical options for unresectable hepatocellular carcinoma (HCC), yet their efficacy remains limited by poor tumor targeting, low response rates, insufficient immune activation, and systemic toxicity. To address these challenges, we establish a "Pave the Way Strategy" combining…
ImmunotherapyAug 17, 2026
Logic-gated nanoregulators: A paradigm shift from drug delivery to pre-programmed multi-target immunotherapy.
Wu Y et al. (+7)
Biomaterials
Cancer immunotherapy has reshaped oncology, yet its broad application is constrained by an immunosuppressive tumor microenvironment and the systemic toxicities of conventional treatments. This review traces the evolution of nanomedicine from a passive drug delivery vehicle to a therapeutic program encoded in a physical structure. The tumor microenvironment poses physical and cellular barriers that operate not as…
Cancer BiologyAug 16, 2026
Mechanical regulation of m<sup>6</sup>A-dependent autophagy sustains cancer stemness and chemoresistance in a viscoelastic tumor microenvironment.
Zhang Y et al. (+10)
Biomaterials
The mechanical properties of the tumor microenvironment fundamentally influence cancer progression, while how viscoelastic cues interface with epitranscriptomic regulation to control cell fate remains poorly understood. Here, a pair of hyaluronic acid-based supramolecular hydrogels with tunable network dynamics are engineered to mimic the viscoelastic properties of tumor ECM. Human osteosarcoma (HOS) cells…
Gene EditingAug 15, 2026
Ultrasensitive and specific detection of Coxsackievirus A10 using the reverse transcription multiple cross displacement amplification combined with CRISPR/Cas12a system.
Cao Y et al. (+7)
Talanta
The escalating global burden of Coxsackievirus A10 (CVA10)-associated hand, foot, and mouth disease (HFMD), coupled with the lack of specific antiviral therapies, has created an urgent need for diagnostic methods that balance sensitivity, speed, and field-deployability, a balance that current molecular tools have yet to achieve. To address this gap, we developed CVA10-RT-MCDA-CRISPR analysis, an integrated platform…
ImmunotherapyAug 15, 2026
A sonogenetic antigen-presenting nanoplatform enables spatiotemporal control of calcium signalling in T cells for enhanced cancer immunotherapy.
Zhao Q et al. (+7)
Biomaterials
Effective T-cell activation plays the critical role in cancer immunotherapy; however, strategies to precisely and sustainably stimulate antitumor T-cell responses while minimizing systemic toxicity remain limited. Here, we develop a sonogenetic artificial antigen-presenting cell (aAPC) platform for remote, spatiotemporally controlled Ca2+ influx in tumor-infiltrating T cells. The platform consists of poly…
Gene EditingAug 12, 2026
A cascade colorimetric sensor based on Meso-UiO-66(Zr)@PtPdNPs nanozyme with triple enzyme activities and RPA-CRISPR/Cas12a for Staphylococcus aureus detection.
Zhou Y et al. (+8)
Talanta
Staphylococcus aureus (S. aureus) is a common foodborne pathogen that can cause severe illnesses such as food poisoning and toxic shock syndrome, posing a significant threat to public health. Therefore, rapid and highly sensitive detection of S. aureus is crucial for ensuring food safety. In this study, a Meso-UiO-66(Zr)@PtPdNPs nanozyme with triple enzyme activities was synthesized and combined with the…
mRNA & VaccinesAug 11, 2026
In Trans RNA Replication of a Defective Self-amplifying RNA Lowers RNA Replication But Enhances Protein Translation.
Moreno Gutierrez DS, Duran Meza AL, Gelbart WM
Journal of molecular biology
RNA replication is fundamental to the life cycle of the large majority of viruses and has attracted increasing interest due to its potential to enhance mRNA expression for vaccines and gene therapy. This process relies on RNA-dependent RNA polymerase (RdRp) genes that, once translated, recognize their cognate mRNAs and replicate them. Self-amplifying RNAs (saRNAs) - "replicons" - can be engineered by incorporating…
Cancer BiologyAug 10, 2026
Surface-enhanced Raman spectroscopy for breast cancer personalized management:From liquid biopsy and intraoperative navigation to therapy monitoring.
Fang Y et al. (+5)
Talanta
Surface-enhanced Raman spectroscopy (SERS) has emerged as a powerful analytical platform for addressing the critical challenges in breast cancer precision diagnostics. This review systematically examines the recent methodological advances that position SERS as a transformative tool across the entire clinical continuum of breast cancer management-spanning non-invasive liquid biopsy screening, intraoperative surgical…
NeurotechnologyAug 9, 2026
Connectome-based graph metrics predict electroconvulsive therapy response in adults with depression.
Ramon F et al. (+17)
Journal of affective disorders
IntroductionElectroconvulsive therapy (ECT) is the most effective intervention for depression, yet no validated biomarkers reliably predict which patients will remit. Large-scale structural and functional dysconnectivity is well-established in major depressive disorder, motivating the use of graph-theoretical metrics to capture network architecture and identify treatment-sensitive markers.MethodsIn a prospective…
Synthetic BiologyOpen accessAug 7, 2026
Metabolic engineering of <i>Escherichia coli</i> for efficient production of d-phenylglycine.
Xiong Y et al. (+8)
Synthetic and systems biotechnology
d-phenylglycine (D-PHG) is a valuable building block extensively used in the synthesis of β-lactam antibiotics and other high-value pharmaceuticals. However, its conventional chemical production relies on expensive starting materials and harsh reaction conditions, while existing biotechnological approaches remain constrained by low production efficiency. In the present work, we established a novel de novo…
Cancer BiologyAug 7, 2026
Self-assembled DNA nanosphere-powered confined-free self-circulating amplifier for high-fidelity microRNA imaging and clinical liquid biopsy.
Jiang J et al. (+4)
Talanta
The development of predictable and thermodynamically stable DNA nanomachines remains challenging for the monitoring of intracellular microRNAs (miRNAs) in complex biological matrices. In this study, a fluorescent biosensor utilizing a confined-free synergistic configuration is presented for the precise detection of miR-21. To mitigate the thermodynamic limitations of homogeneous catalytic hairpin assembly (CHA), a…
Synthetic BiologyOpen accessAug 6, 2026
Metabolic engineering of <i>Saccharomyces cerevisiae</i> for <i>de novo</i> biosynthesis of isoorientin.
Song Z, Zhang F, Qi X
aBIOTECH
The flavonoid glycoside isoorientin has demonstrated antitumor, cardioprotective, and gut-protective activities, as well as potential applications as a natural biopesticide and antimicrobial agent. However, large-scale production and industrial development of isoorientin are limited by its low abundance in plants. In this study, we used metabolic engineering to construct an isoorientin-producing budding yeast…
Drug DiscoveryOpen accessAug 4, 2026
Context matters in PROTAC design: navigating the trade-off between degradation and developability.
Zhang B et al. (+11)
Journal of enzyme inhibition and medicinal chemistry
Proteolysis-targeting chimaeras (PROTACs) couple target recognition to ubiquitin-dependent degradation, but their translation requires coordinated optimisation of degradation efficiency and developability. This review frames PROTAC design as a context-dependent medicinal chemistry problem rather than modular assembly of a warhead, linker and ubiquitin ligase (E3) recruiter. Linker length, rigidity, and exit vectors…
Single-Cell & OmicsAug 2, 2026
High-throughput single-cell metabolomics to reveal the hepatotoxicity of 77PDQ exposure in mice.
Liu N et al. (+6)
Talanta
Elucidating the effects of pollutants at the level of primary single cells is of great significance for an in-depth understanding of their health risks and toxicological mechanisms. N,N'-bis (1,4-dimethylpentyl)-p-phenylenediamine quinone (77PDQ) is an emerging environmental contaminant with multiple biological toxicities; however, its toxic effects at the primary single-cell level remain unexplored. In this study…
Drug DiscoveryOpen accessAug 1, 2026
A DoE-Dual centrifugation-driven screening platform for liposomal incorporation of poorly soluble APIs: Application to the PROTAC ACBI2.
Jaki M et al. (+4)
International journal of pharmaceutics: X
A fast and efficient screening platform is presented for formulating poorly soluble drugs, such as proteolysis-targeting chimeras (PROTACs), into liposomes. Driven by Design of Experiments (DoE) and powered by dual centrifugation, this platform enables high-throughput parallel preparation alongside a newly validated, single-run HPLC method for the simultaneous quantification of all lipid components and hydrophobic…
Longevity & AgingJul 28, 2026
Pannexin1 promotes cellular senescence by triggering mtDNA release to activate the cGAS-STING pathway.
Li J et al. (+5)
Biochimica et biophysica acta. Molecular basis of disease
Cellular senescence is a pivotal driver of the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). We previously identified Pannexin 1 (Panx1) as an endoplasmic reticulum (ER)-resident calcium (Ca2+) leak channel that promotes renal tubular senescence; however, the precise downstream effectors remain elusive. Here, we establish a novel mechanistic link between Panx1 and the cGAS-STING pathway…
Single-Cell & OmicsOpen accessJul 16, 2026
scYeast: a biological-knowledge-guided foundation model on yeast single-cell transcriptomics.
Fan X et al. (+4)
Synthetic and systems biotechnology
Though large-scale pre-trained models are vital for foundational cell modeling, most of them focus on human or mouse systems, with less emphasis on model organisms like yeast (Saccharomyces cerevisiae), and fail to use existing biological prior knowledge effectively. Here, we present scYeast, the first foundational cell model for yeast single-cell transcriptomics that effectively embeds biological priors. scYeast…
mRNA & VaccinesPreprint · not peer reviewedJul 15, 2026
Safety and Immunogenicity of SW-BIC-213, a Modified COVID-19 Lipo-Polyplex mRNA Vaccine, in Laotian Healthy Adults Aged 18 Years and Above: A Phase 1/2 Trial
Yuan Y et al. (+9)
Preprints.org
We evaluated the safety and immunogenicity of SW-BIC-213, a Lipo-Polyplex (LPP)-based mRNA vaccine against SARS-CoV-2, administered as a two-dose regimen 21 days apart in healthy adults in Laos. In this phase 1/2 trial, healthy adults aged 18–60 years (phase 1) or ≥18 years (phase 2) were enrolled at Mahosot Hospital (Vientiane) and Champhone District Hospital (Savannakhet). In phase 1, 41 participants received…
mRNA & VaccinesOpen accessJul 13, 2026
Optimized seasonal influenza mRNA vaccine compositions demonstrate safety and enhanced immunogenicity in a phase 2 study.
Fierro C et al. (+8)
Human vaccines & immunotherapeutics
Seasonal influenza causes considerable morbidity and mortality, with influenza A and B viruses driving most influenza-associated hospitalizations and deaths. Vaccination remains a key influenza prevention strategy; however, current seasonal influenza vaccines based on traditional platforms provide inconsistent protection. Messenger RNA - based vaccines may offer several key advantages over other vaccines, including…
AI & Protein DesignJul 9, 2026
AlphaFold-based peptide structure prediction: Opportunities, limitations, and future directions.
Zhang B et al. (+3)
Biotechnology advances
Accurate prediction of peptide structures and peptide-receptor complexes is essential for rational peptide drug development. However, the inherent conformational flexibility of short and disordered peptides presents a fundamental challenge. The AlphaFold model series, which has progressed from AlphaFold2 through AlphaFold-Multimer to AlphaFold3, has substantially advanced computational peptide structure prediction…
Synthetic BiologyOpen accessJun 18, 2026
Metabolic engineering of <i>Escherichia coli</i> based on adaptive evolution and omics technology for highly efficient l-valine production under oxygen-limited conditions.
Zhang H et al. (+10)
Synthetic and systems biotechnology
In industrial production, the yield of desired targets derived from carbon sources is frequently diminished by the competitive influence of cellular metabolism within microbial cell factories. The bioproduction of l-valine exemplifies a classic process that is confronted with such a dilemma, substantially hindering its economic industrial-scale production. In this study, we aim to engineer a cell factory capable of…
mRNA & VaccinesJun 14, 2026
A narrative review of COVID-19 epidemiology and mRNA vaccine impact in children <12 years during the omicron era (November 2021 - December 2025).
Zheng Z et al. (+6)
Expert review of vaccines
IntroductionCOVID-19 continues to pose a burden in children under 12 years of age during the Omicron era (November 2021 - December 2025). Following Omicron's emergence, SARS-CoV-2 seroprevalence increased rapidly, with most children infected by ages 2-4 years. Pediatric hospitalization rates declined after the initial Omicron wave but remained elevated in children under 2 years and in those with underlying…
Longevity & AgingJun 6, 2026
Polarity probes targeting different organelles based on aza-coumarin for monitoring ferroptosis and cellular senescence.
Ni WP et al. (+4)
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
Polarity within the cellular microenvironment is a key physical parameter that regulates multiple biological processes, and its dysregulation is closely associated with various diseases. This work designed and synthesized three polarity-sensitive fluorescent probes (3a-3c) based on an aza-coumarin fluorophore with a D-π-A structure, leveraging the intramolecular charge transfer (ICT) mechanism. The optical…
Longevity & AgingJun 5, 2026
Orbital hybridization-mediated nanozymes reverse cellular senescence for aged bone regeneration.
Wang Y et al. (+9)
Biomaterials
The regeneration of aged bone is severely compromised by a deteriorating microenvironment characterized by excessive reactive oxygen species (ROS) and consequential endoplasmic reticulum stress (ERS). Herein, we report a biomimetic nanozyme engineered through synergistic p-d orbital hybridization and youthful membrane camouflage to precisely reverse this degenerative cascade. The designed Cu-Sn dual-atom core…
Longevity & AgingOpen accessJun 2, 2026
The role of cellular senescence in immune-metabolic features and prognosis of ovarian cancer: an integrated analysis based on single-cell sequencing and multi-omics data.
Li Y et al. (+7)
GeroScience
Ovarian cancer is characterized by a high recurrence rate, and platinum resistance often contributes to poor patient outcomes. Cellular senescence can influence the tumor microenvironment, metabolic status, and immune regulation. However, the role of senescence-associated genes (SAGs) in the heterogeneity, prognosis, and treatment-related features of ovarian cancer remains to be further clarified. This study…
Cell & Gene TherapyMay 19, 2026
<i>In vivo</i> CAR-T for the treatment of autoimmune diseases: Current progress and future directions.
Zhao Y et al. (+4)
Genes & diseases
Autoimmune diseases are a clinical challenge because current immunosuppressive therapies fail to eliminate pathogenic immunocytes, such as autoreactive B cells, plasma cells, and antigen-presenting cells, which induce chronic inflammation. Chimeric antigen receptor T (CAR-T) cell therapy offers a targeted strategy to eliminate these disease-driving populations. Early ex vivo CAR-T cell studies on severe autoimmunity…
mRNA & VaccinesOpen accessMay 19, 2026
Enhanced immunogenicity and dose-sparing efficacy of self-amplifying RNA vaccines against seasonal influenza across subtypes.
Huang M et al. (+30)
Emerging microbes & infections · 2 citations
Recent clinical data on seasonal influenza mRNA vaccines have demonstrated suboptimal efficacy against the influenza B virus (IBV). We employed sequence optimization strategies that successfully enhanced the antigen expression of hemagglutinin (HA) and developed mRNA vaccine candidates targeting the WHO-recommended strains. When administered at a low dose (0.1 μg), both mono-and trivalent influenza A mRNA vaccines…
mRNA & VaccinesOpen accessApr 22, 2026
Self-amplifying RNA (saRNA) and circular RNA (circRNA) vaccines: Progress, evidence gaps, and translational pathways for durable and scalable immunization.
Okechukwu Paul-Chima U et al. (+4)
Human vaccines & immunotherapeutics · 9 citations
Self-amplifying RNA (saRNA) and circular RNA (circRNA) are emerging vaccine modalities that extend conventional, non-replicating mRNA platforms. Self-amplifying RNA encodes a replicase that amplifies intracellular RNA templates, enabling high antigen expression at substantially lower doses than non-replicating mRNA. Circular RNA has a covalently closed topology that confers resistance to exonucleases and supports…
Single-Cell & OmicsOpen accessMar 27, 2026
Single-cell sequencing-guided discovery of narciclasine as a dual VCAM-1/ICAM-1 inhibitor for atherosclerosis management.
Wang Y et al. (+5)
Genes & diseases
Atherosclerosis (AS) remains a leading cause of cardiovascular morbidity and mortality worldwide, with current treatments focused primarily on reducing low-density lipoprotein levels while failing to repair damaged endothelial cells, thus highlighting the urgent need for novel therapeutic drugs. To address this challenge, we analyzed human AS patient single-cell RNA sequencing datasets to identify disease-driving…
NeurotechnologyOpen accessMar 19, 2026
Application and prospects of brain-computer interface technology for motor function reconstruction after brachial plexus injury.
Song S, Li X, Pan P
Annals of medicine
BackgroundBrachial plexus injury (BPI) is a severe peripheral nerve disorder leading to significant upper limb motor dysfunction. While traditional surgeries like nerve grafting and tendon transfer exist, functional outcomes are often suboptimal due to biomechanical limitations and slow neural recovery. Brain-computer interface (BCI) technology has emerged as a promising innovative pathway for motor function…
MicrobiomeFeb 4, 2026
Host diets drive microbiome evolution and functional divergence.
Nguyen KL, Xia JS, Mei W
Genes & diseases
Substantial variation in gut microbiome function across individuals underscores the pivotal role of the host in shaping microbial diversity. Increasing evidence indicates that diet is a major selective force driving the evolutionary trajectory of the gut microbiome. In response to dietary inputs, the microbiome adapts by shifting the relative abundance of taxa, species, and sub-strains. The gut microbiome also…
mRNA & VaccinesOpen accessJan 6, 2026
Influence of the administration route and dose on the expression and antibody responses of a reporter and avian influenza self-amplifying mRNA vaccine in poultry.
Snoeck J et al. (+4)
The veterinary quarterly
Vaccination is routinely used in industrial poultry to control infectious diseases. Vaccines based on mRNA and self-amplifying RNA (saRNA) are approved for human use, but research on their application in poultry is limited. In this study the saRNA vaccine platform is evaluated in poultry. First, a luciferase-encoding saRNA (luc-saRNA) was tested as a model vaccine across different administration routes and doses in…
AI & Protein DesignOpen accessAug 25, 2025
Performance of pyDock in 8th CAPRI: Energy-Based Scoring Applied to Docking and AlphaFold Models.
Rodríguez-Lumbreras LA et al. (+5)
Proteins
The 8th CAPRI edition has shown a significant evolution in the field of protein-protein complex structure prediction. We have participated in all 11 targets proposed in this edition, involving domain-domain, protein-protein, protein-peptide, and protein-DNA interactions, including homo- and hetero-meric interfaces. Our prediction strategy has significantly evolved during this edition due to the appearance of…
AI & Protein DesignOpen accessJul 14, 2025
Biomolecular Interaction Prediction in the Pre- and Post-AlphaFold Era: The 8th CAPRI Evaluation.
Lensink MF et al. (+5)
Proteins · 6 citations
We report on the 8th CAPRI Evaluation period, capturing the assessment of CAPRI Rounds 47 to 55 (excluding the CASP and COVID-related Rounds), which have witnessed the transition to AI-driven prediction tools such as AlphaFold and related alternatives. The prediction Rounds in this evaluation are characterized by a high level of difficulty due to various factors, including the nature of the targets, the intricacy of…
AI & Protein DesignJun 6, 2025
Modeling CAPRI Targets of Round 55 by Combining AlphaFold and Docking.
Singh A et al. (+3)
Proteins
In recent years, the field of structural biology has seen remarkable advancements, particularly in modeling of protein tertiary and quaternary structures. The AlphaFold deep learning approach revolutionized protein structure prediction by achieving near-experimental accuracy on many targets. This paper presents a detailed account of structural modeling of oligomeric targets in Round 55 of CAPRI by combining deep…
AI & Protein DesignApr 1, 2025
Protein Complex Structure Prediction With AlphaFold-Enhanced HDOCK in CAPRI Rounds 47-55.
Li H et al. (+3)
Proteins
Protein-protein interactions play a critical role in numerous biological processes, and understanding these interactions is essential for deciphering cellular mechanisms and designing therapeutic interventions. Predicting protein-protein complex structures by computational methods is an important approach to studying protein-protein interactions. The CAPRI (Critical Assessment of PRediction of Interactions)…
AI & Protein DesignOpen accessJan 20, 2025
AlphaFold and Docking Approaches for Antibody-Antigen and Other Targets: Insights From CAPRI Rounds 47-55.
Gowthaman R et al. (+4)
Proteins · 5 citations
Accurate modeling of the structures of protein-protein complexes and other biomolecular interactions represents a longstanding and important challenge for computational biology. The Critical Assessment of PRedicted Interactions (CAPRI) experiment has served for over two decades as a key means to assess and compare current approaches and methods through blind predictive scenarios, highlighting useful strategies, and…