Biology subjects

Pang, J.

Publications and source records attributed to Pang, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Transcriptomic similarity guides source selection beyond tissue lineage

Perturbational and pharmacogenomic maps remain incomplete across cellular contexts, leaving a practical source-selection question before response prediction: which measured context should inform an unmeasured target? We tested whether baseline transcriptomic similarity ranks candidate sources for held-out targets, separating source ranking from aggregation and transfer-uncertainty decisions. Similarity tracked matched-response concordance in LINCS and GSE306429; selected-source utility exceeded random expectation in GSE306429 ({Delta}U = 0.034; P = 0.002) and in exact-time-matched MIX-Seq tasks ({Delta}U = 0.046). In the full GDSC2 analysis, the drug-balanced ranking effect was 0.359 (95% CI, 0.337-0.383). In a lineage-restricted analysis of the same eligible subset, within-tissue ranking remained positive at 0.130 (95% CI, 0.119-0.141), retaining 35.8% of the same-subset global effect (0.363; 95% CI, 0.342-0.386). Global transcriptomic top-1 selection exceeded tissue-matched random selection by 0.154 (95% CI, 0.143-0.164). Thus, baseline similarity adds source-ranking information after tissue matching in the evaluated setting, while ranking alone does not resolve whether to aggregate sources or how to quantify transfer uncertainty.

bioinformatics↗

bioRxiv2026

From Prompt to Provenance: BloClaw, a Capability-Gated AI4S Workstation for Auditable Computational Biology

Scientific agents can produce plausible answers while remaining unable to establish whether the computation behind an answer is executable, recoverable, or reproducible. We present BloClaw, an AI4S workstation built around a simple principle: a scientific agent should know what it can do, show how it did it, and state what remains unvalidated. Each capability declares an execution state, input constraints, dependencies, expected outputs, and scientific limitations. Natural-language requests are translated into structured tasks, validated against this registry, executed through scientific tools, and recorded in a provenance-aware Living Lab Notebook. The system is designed to detect invalid inputs, failed tool calls, missing dependencies, and remote timeouts, and to route them to repair, retry, or escalation. The implemented and tested scope comprises RDKit-based molecular property and rule screening, protein structure analysis, docking-pose inspection, 3D visualization, and structured reporting. We demonstrate the workflow on a PubChem-retrieved osimertinib structure and a supplied 6LU7 docking artifact: the former yields deterministic descriptors (molecular weight 499.619 Da, cLogP 4.5098, TPSA 87.55 A^2), while the latter contains 2,387 protein ATOM records, 309 residues, and nine pose records. These examples are workflow demonstrations, not efficacy or affinity studies. Beyond retrospective prediction, the manuscript specifies a prior-minimized constructive mode in which a desired function is compiled into explicit physical, chemical, and systems constraints, candidate mechanisms are simulated, and observations are reintroduced for calibration and falsification; this is a proposed extension rather than a result of the present case studies. We describe an evaluation protocol that compares BloClaw with a standard single-agent workflow and fixed-script execution using task completion, scientific correctness, recovery success, provenance completeness, reproducibility, human review time, latency, and cost. This manuscript reports the system design, verified capability boundary, deterministic software artifacts, and a reproducible evaluation protocol; it does not claim benchmark improvements before those experiments are run. BloClaw is an execution and accountability layer for AI-assisted research, complementing expert review and experimental validation rather than replacing them.

bioinformatics↗

bioRxiv2026

Long-read single cell transcriptomics uncovers isoform preferences in developing human retina

Retinal development has been extensively studied and key transcriptional regulators that drive fate decisions have been identified for major cell classes. These findings were confirmed and deepened in recent years with the advance of single cell RNA sequencing (Scrase). However, many processes that guide progenitor to postmitotic cell differentiation remain elusive, especially since some genes seem to yield different cell populations without apparent correlation with expression level or timing. Here, differential transcript isoform usage might play a role in diversifying the function of developmental genes. In short-read based scRNAseq, isoforms can only be identified if a read maps to a unique sequence or exon junction. However, due to the sparsity and very short reads, these events are extremely rare. We combined a commercial scRNAseq kit, that produces barcoded, full-length cDNA with Oxford Nanopore Technologies based long-read sequencing to generate the first single cell long-read sequencing dataset of fetal human retina. It can help elucidate the role of alternative splicing in retinal development and guide the design of transcript-specific gene therapies for retinal regeneration.

developmental biology↗

bioRxiv2026

MiRNA let-7a-5p Ameliorates Pulmonary Fibrosis by Suppressing TGFBR1-Mediated Endothelial-to-Mesenchymal Transition

Background Idiopathic Pulmonary Fibrosis (IPF) is a fatal chronic lung disease with limited therapeutic options. While alveolar epithelial injury and fibroblast activation are well-studied, endothelial-mesenchymal transition (EndoMT) is emerging as a critical pathogenic mechanism. The regulatory role of exosomal miRNAs in pulmonary fibrosis remains unclear. This study investigates serum exosomal miRNAs, particularly let-7a-5p, in modulating EndoMT during the onset of pulmonary fibrosis. Methods Clinical cohorts of IPF patients and healthy controls were enrolled. Serum exosomal miRNAs were profiled, followed by differential expression and functional enrichment analyses. In vitro experiments involved human pulmonary artery endothelial cells (HPAECs) transfected with let-7a-5p mimic or inhibitor. Dual-luciferase reporter assays confirmed the binding between let-7a-5p and TGFBR1. HPAECs were co-cultured with lung epithelial cells to examine paracrine signaling. In vivo studies used a bleomycin-induced mouse model with let-7a-5p agomir administration. Assessments included histopathological staining, hydroxyproline content, Western blot, qPCR, micro-CT, and pulmonary function tests. Results Let-7a-5p was significantly downregulated in serum exosomes from IPF patients, correlating with clinical indicators. Mechanistically, let-7a-5p directly bound the TGFBR1 3'UTR to inhibit its expression. Inhibition of let-7a-5p upregulated -SMA, FN1, smad2/3 phosphorylation, and collagen I, while downregulating CD31 and VE-cadherin. Therapeutically, let-7a-5p mimic reversed bleomycin-induced EndoMT and suppressed epithelial-mesenchymal transition (EMT) via paracrine signaling. Mice administered agomir showed reduced fibrosis, improved lung function, and suppressed TGF-{beta}/Smad signaling. Conclusion Serum exosomal let-7a-5p suppresses pulmonary fibrosis by targeting TGFBR1 to inhibit EndoMT. Its downregulation in IPF patients correlates with disease progression, highlighting its biomarker potential.

molecular biology↗

bioRxiv2026

Pan-Peroxisome Proliferator-Activated Receptor Agonist IVA337 Alleviates Secondary Lymphedema via Inhibiting TGFβ/SMAD2/3 Signaling Pathway

Lymphedema is a chronic disease characterized by impaired lymph drainage and accumulation of protein-rich interstitial fluid, which progresses to develop irreversible fibrosis. Importantly, effective therapies and treatments are lacking to alleviate and mitigate the disease. The pathological inflammation and fibrogenesis underlying lymphedema prompted us to evaluate a preclinical medicine IVA337, a pan-peroxisome proliferator-activated receptor (PPAR) agonist that improves liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH) by activating three PPAR isoforms (, {beta}/{delta}, {lambda}), which play critical roles in lipid metabolism, anti-inflammation responses, and anti-fibrogenesis. Here, we investigate the therapeutic effects of IVA337 during the early stage of surgery-induced secondary lymphedema in mice and explored the underlying mechanisms. IVA337 administration alleviated lymphedema progression, improved lymphatic drainage, reduced dermal thickness, and resolved lymphatic vessel dilation. Mechanistically, IVA337 suppressed the TGF{beta}/SMAD2/3 signaling pathway, reduced immune cells infiltration, and improves lymphatic vessels integrity. In human dermal lymphatic endothelial cells (HDLECs), IVA337 attenuated TGF{beta} induced SMAD2/3 phosphorylation and preserved the expression of cell junction Claudin5, reduced VE-Cadherin-stained cell-cell gaps. Collectively, our findings demonstrate that IVA337 protects against early stage lymphedema by inhibiting TGF{beta}/SMAD2/3-mediated inflammatory and fibrotic responses. This study provides a potential therapeutic strategy to improve lymphatic function during the early phase of lymphedema and prevent progressive fibrosis in patients with lymphedema and related disorders.

pathology↗

bioRxiv2026

CXCL12/CXCR4 Governs Lymphatic Valve Formation Through Flow Dependent AKT/FOXO1/FOXC2 Activation

BackgroundLymphatic valves are specialized structures within lymphatic vessels that ensure unidirectional lymph transport. Defective lymphatic valve formation is associated with lymphedema, a chronic disease characterized by impaired lymph drainage and the accumulation of protein-rich interstitial fluid. Lymphatic valves form during late embryonic stages in mice, with oscillatory shear stress implicated in regulating the molecular mechanisms which control lymphatic valve formation. However, the molecular mechanisms governing lymphatic valve formation remain incompletely understood. Although CXCR4 is regulated by shear stress in blood vessels, whether CXCL12/CXCR4 signaling regulates lymphatic valve formation and the underlying molecular mechanisms remain unknown. MethodsTo investigate the roles of CXCR4 in the regulation of lymphatic valve development, we utilized lymphatic endothelial cell (LEC)-specific Cxcr4 knockout (Flt4CreERT2, Cxcr4f/f) mice. To determine the source of CXCL12, major ligand for CXCR4 in the mesentery, we used global Cxcl12-/-, and Cxcl12-DsRed knock-in/knockout (KIKO) reporter mice, as well as conditional Cxcl12 knockout mouse lines. To determine the molecular mechanisms by which CXCL12/CXCR4 regulates lymphatic valve development, primary human dermal LECs were exposed to oscillatory shear stress (OSS) to mimic valve-associated flow, followed by analysis of downstream signaling pathways and valve related gene expression. ResultsLEC-specific loss of CXCR4 displayed impaired lymphatic valve development. Flt4CreERT2, Cxcr4f/f mice showed a significant reduction in valve numbers in embryonic mesenteric lymphatic vessels. Similarly, reduced valve numbers were observed in Cxcl12-/- embryos, indicating CXCL12/CXCR4 is required for embryonic mesentery collecting lymphatic valve formation. Cxcl12-DsRed KIKO mice revealed that blood vessels, opposed to nerves, were the major source of CXCL12 in the embryonic mesentery. In align with this finding, EC-specific Cxcl12 deletion recapitulated defective valve phenotypes observed in Cxcl12-/- embryos. Mechanistically, CXCR4 knockdown in primary human dermal LECs attenuated OSS induced phosphorylation of AKT and FOXO1, leading to increased nuclear localization of FOXO1 and reduced expression of FOXC2, an essential transcription factor governing lymphatic valve development. Consistent with these findings, lymphatic valves of LEC-Cxcr4 deficient mice exhibited increased FOXO1 nuclear localization. Importantly, pharmacological activation of AKT reduced FOXO1 nuclear accumulation and restored lymphatic valve numbers in LEC-Cxcr4 deficient mesenteric lymphatic vessels. ConclusionsOur findings reveal CXCL12/CXCR4 signaling acts as a critical regulator of lymphatic valve development. CXCL12/CXCR4 signaling integrates into the flow dependent AKT/FOXO1/FOXC2 signaling axis to coordinate lymphatic valve development and morphogenesis. Taken together, our study uncovers a previously unknown role of CXCL12/CXCR4 signaling pathway in the regulation of lymphatic valve development. Targeting CXCL12/CXCR4/AKT/FOXO1 axis may represent a promising therapeutic strategy for improving lymphatic valve development to improve lymphatic function for the treatment of lymphedema.

developmental biology↗

bioRxiv2026

Stimulating neurogenesis of distinct retinal lineages in human retinal pigmented epithelium (RPE) with proneural transcription factors

There are currently few promising approaches for treatment of photoreceptor pathologies: for example, gene therapy to augment or replace mutated genes, has proven successful in preclinical studies, and some of these therapies are moving towards the clinic. Another approach aims to unlock the inherent stem-cell potential of non-neuronal retinal cells to regenerate neurons in situ. This line of research is based on the discovery that some vertebrates can restore even severely damaged retina from RPE with all the necessary cell types to regain full functionality. To determine whether this approach can be applied to humans, we established a robust in vitro culture system using fetal human RPE, and employed a barcode-multiplexed, single cell RNAseq based screen to find factors that would reprogram human RPE into a photoreceptors. With this approach we were able to identify NEUROD1 as a complimentary factor to ASCL1. Their combined overexpression together with a treatment with bFGF and Activin A inhibitor produced RPE-derived neuronal cells with expression patterns characteristic of photoreceptors and other lineages.

Developmental Biology↗

bioRxiv2026

Cellfm-datasets: A Unified Data Infrastructure for Single-Cell and Spatial Transcriptomics Foundation Model Pretraining

Large-scale cell foundation models are increasingly limited not only by model architecture, but also by the data infrastructure required to repeatedly sample sparse transcriptomic profiles from out-of-core cohorts. AnnData/H5AD has become a standard exchange format for single-cell and spatial omics analysis, yet its HDF5-backed layout is not designed for high-frequency random mini-batch loading under multi-worker and distributed pretraining. We present Cellfm-datasets, a data infrastructure artifact that converts H5AD cohorts into a self-describing compressed sparse row (CSR) memmap layout and exposes the resulting corpus through Hugging Face Dataset and IterableDataset interfaces. The artifact stores a shared gene vocabulary, per-sample metadata, optional spatial coordinates, observation metadata, manifests, and checksums, and reconstructs sparse cell or group records at runtime without dense expansion. A unified sampling abstraction supports random-cell groups, manifest-defined biological regions, and coordinate-based spatial blocks, with deterministic sharding across distributed ranks and data-loader workers. Spatial demonstrations on P14 mouse brain transcriptomics sections illustrate region- and block-level sampling over real anatomical structures. In controlled benchmarks on a public heterogeneous ModelScope scRNA-seq subset, Cellfm-datasets reached 60,571 {+/-} 1,734 samples/s in single-core random loading, scaled to approximately 160,000 samples/s with eight workers, and maintained near-constant process-private memory while reading up to one million cells. By moving sparse single-cell and spatial corpora from model-specific loader code into reusable, validated, and framework-native dataset artifacts, this design may reduce the engineering burden of reproducible cell foundation model pretraining and make repeated training runs, model comparisons, and mixed-modality data reuse easier to standardize. Code availabilityhttps://github.com/PangJiangShuan/cellfm-datasets

bioinformatics↗

bioRxiv2026

Multi-omics analysis of type II diabetic wound healing reveals CD44-mediated immune cell crosstalk dysfunction in mice and humans

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the United States and is associated with diabetic foot ulcers (DFU) and their impaired, often chronic, wound healing. The T2DM mouse model with dysfunctional leptin receptor (db/db) has been used in basic and translational studies of wound healing due to its systemic phenotypes (hyperphagia, hypometabolism, obesity, T2DM) and its notable delayed skin wound healing. However, a characterization of the temporal cellular dynamics of the db/db wound healing model has not been performed, nor has the model been systematically compared to human DFUs. We performed the first comprehensive single-cell, multi-omic analysis of dermal cells in diabetic (db/db) compared to non-diabetic (ND) mice across three time points ranging from the inflammatory to the delayed proliferative and resolution phases of healing. Single-cell transcriptomics were uniquely linked to their corresponding cells surface protein expressions of cell-specific receptors, including immune cells (CD45) such as neutrophils (CD11b, Ly6G), monocytes/macrophages (CD11b, F4/80, CD11c, Ly6C) and T lymphocytes (CD3, CD4), and dermal cells such as endothelial cells (CD31) and fibroblasts (CD26, CD140a), and showed high concordance between protein cell markers and their gene expressions in major cell types. Differential multi-omic analyses characterized two neutrophil (Tnfaip3+Sod2+Ly6G+, Csf3r+Fos+Ly6G+), three monocyte/macrophage (F4/80highCD11bhigh, Ly6chighCD11bhigh, CD11chighCD11blow) and three fibroblast (Pi16+Dpp4+CD26high, Lrrc15+Tnc+CD140ahigh, Cilp+Mgp+CD26low) subtypes showing dysregulated dynamics across the time course of healing in db/db vs ND mice. Notably, NETotic Tnfaip3+Sod2+Ly6G+ neutrophils and phagocytic F4/80highCD11bhigh macrophage subtypes were drastically up-regulated in diabetic wounds. Differential cell-cell communication analyses revealed striking differences in crosstalk dynamics between fibroblast, macrophage and neutrophil subtypes in the early phase of healing, and ligand-receptor interactome analyses identified CD44 as the hub of dysregulated immune cell interactions in diabetic wounds, implicating cell adhesion, migration and inflammatory pathways, especially those mediated by ICAM1. Inhibition of CD44 using blocking antibodies in primary macrophages from db/db mice and via intradermal injections in db/db mice significantly normalized the early wound immune dysfunction, in part by inhibiting ICAM1 and reversing the excessive neutrophil influx into diabetic wounds. A new integrated dataset of single-cell human chronic wound studies revealed similar CD44-mediated immune cell dysfunctions in diabetic vs non-diabetic foot ulcers, pointing to CD44 as a promising therapeutic target for T2DM-associated chronic wounds.

molecular biology↗

bioRxiv2026

Transcriptional regulators predicted to drive macrophage dysregulation during impaired wound healing in diabetic mice

Dysregulation of Mo/M{varphi} activity is known to contribute to impaired healing in diabetes; however, the mechanisms underlying this dysregulation are not well understood. In this study, we used a variety of bioinformatics approaches along with our time series scRNA-seq data on wound Mo/M{varphi} from non-diabetic and diabetic mice to identify transcriptional regulators (TRs) that drive Mo/M{varphi} state transitions during normal and impaired healing. First, we used the Lamian framework and our newly developed Pseudotime Graph Diffusion method to show that state transitions from early stage phenotypes to later stage reparative and antigen presenting phenotypes characteristic of normally healing wounds are impaired and that transitions to inflammatory, foam cell-like, and Lyve-1+ M{varphi} phenotypes are enhanced during impaired healing of diabetic mice. Using our BITFAM model, we identified a broad range of TRs predicted to be preferentially active in each cell state and using CellOracle, we performed in silico perturbation to identify groups of TRs predicted to drive cell state transitions along multiple trajectories (e.g. CEBPA, IRF8), whereas other TRs were predicted to drive cell state transition towards reparative phenotypes (e.g. NR1H3, NR3C1) or towards an antigen-presenting phenotype (e.g. IRF4, OGT). Selected findings were validated using existing experimental data, confirming the usefulness of this approach. In conclusion, we identified TRs that likely drive Mo/M{varphi} state transitions towards desirable and undesirable phenotypes for wound healing. These findings provide insight into novel targets for altering Mo/M{varphi} phenotypes to promote healing of diabetic wounds.

immunology↗

bioRxiv2026

A Novel Monocyte-derived Antigen Presenting Cell-T regulatory Cell Axis Contributes to Skin Wound healing and is Impaired in Diabetic Mice

Despite a vast literature on the role of macrophages in wound healing, the role of dermal monocyte (Mo)-derived antigen presenting cells (APC) has received scant attention. Using scRNAseq and flow cytometry, we identify a population of APC that is prominent in wounds of non-diabetic mice but is reduced in wounds of diabetic mice. Using adoptive transfer experiments and Ccr2 knockout mice, we demonstrate that wound APC are derived primarily from Mo and that the diabetic wound environment inhibits differentiation of Mo into APC. We also show that Mo-specific Irf4 knockout mice exhibit reduced differentiation of Mo into APC, decreased levels of IL27 and numbers of activated Treg cells in wounds. and impaired wound healing. Importantly, adoptive transfer of bone marrow Mo that express Irf4 into wounds of Mo-specific Irf4 knockout mice rescued levels of wound APC and activated Treg, as well as wound healing. Local administration of recombinant IL27 into wounds of these mice also rescued levels of activated Treg in wounds, along with wound healing, Together, these findings identify a novel pathway in which IRF4 induces Mo differentiation into APC in wounds, which in turn produce IL27 that activates Treg to promote healing. This pathway is impaired in wounds of diabetic mice, which provides a novel target to improve diabetic wound healing.

immunology↗

bioRxiv2026

Pseudotime graph diffusion for post hoc visualization of inferred single-cell trajectories

Visual representations are widely used to interpret trajectories in single-cell data; however, they do not always faithfully capture inferred trajectory structure. As a result, interpretation of cellular dynamics and downstream analyses may be compromised. Here, we present Pseudotime Graph Diffusion (PGD), a lightweight and interpretable post hoc framework for smoothing cell-level features along pseudotime. PGD operates by performing random-walk diffusion on a pseudotime graph, propagating information along inferred trajectory paths to enhance continuity and structure. We demonstrate that PGD-smoothed embeddings improve visualization of increasingly complex inferred trajectories of monocytes and macrophages during wound healing. We further show that PGD extends naturally to trajectory-aware gene expression smoothing and scales to atlas-sized datasets. By improving agreement between visual representations and inferred trajectories, PGD enables more faithful interpretation of dynamic cellular processes.

bioinformatics↗

bioRxiv2025

OmniCell: Unified Foundation Modeling of Single-Cell and Spatial Transcriptomics for Cellular and Molecular Insights

A cells transcriptional programme is not fully defined by gene expression alone, but by the tissue context in which that programme is enacted. Single-cell RNA sequencing resolves molecular identity after dissociation, whereas spatial transcriptomics preserves tissue architecture but remains constrained by assay-specific sparsity and gene coverage. Here we present OmniCell, a tissue-contextual transcriptomic foundation model pretrained on 67 million dissociated and spatially resolved profiles. By integrating gene identity, expression magnitude and tissue context, OmniCell links transcriptional programmes to the cellular neighbourhoods and anatomical contexts in which they operate. OmniCell organised transcriptomes across molecular, cellular and tissue scales. It recovered cell-type-specific programmes and tissue-aligned gene modules, preserved robust cell-state structure across batches, species and rare populations, and improved the reconstruction of spatial cell identity, anatomical domains and cell-type composition. In human liver cancer Stereo-seq data, OmniCell resolved a tumour-margin transition zone characterised by immune infiltration, acute-phase inflammation, coagulation/complement activity and metallothionein-linked metal-ion detoxification. Contextual gene-embedding similarity analysis showed that gene relationships differed across tumour core, transition-zone and paratumour/adjacent non-malignant niches, indicating that OmniCell captures tissue-dependent gene function rather than expression similarity alone. In mouse brain development and macaque cortex, spatial virtual perturbations mapped regulatory genes onto stage- and region-specific anatomical programmes. Together, these results establish tissue context as a primary axis of transcriptomic representation and provide a framework for studying how cellular programmes acquire context-dependent biological meaning in intact tissues.

bioinformatics↗

bioRxiv2025

The Clearance of Human Cytomegalovirus Using CRISPR/Cas9 RNA Lipid Nanoparticles

Human cytomegalovirus (HCMV), a DNA virus, poses significant health risks to immunocompromised and immunosuppressed individuals and newborns. Clinical antiviral drugs like ganciclovir inhibit viral replication but have toxicities, are ineffective against drug-resistant strains, and cannot destroy HCMV DNA. CRISPR/Cas9 can cleave DNA, but has not been used therapeutically to target and degrade HCMV DNA in cells post-infection. We developed an all-in-one CRISPR/Cas9 RNA lipid nanoparticle (LNP) that clears established HCMV infections, permits rapid updating to combat resistance and is effective against multiple strains. Bioinformatic analyses identified essential, conserved viral genes as CRISPR/Cas9 targets. A delivery material screen revealed that antiviral activity was dependent on the ionizable lipid and LNP composition. Our lead formulation, {beta}N2-40, inhibited up to 93.5% of HCMV infection with a single treatment. Furthermore, multitargeting {beta}N2-40 LNPs demonstrated antiviral kinetics and a safety profile similar to ganciclovir, making it a compelling alternative to existing small-molecule antiviral drugs.

bioengineering↗

bioRxiv2025

Decoding the fibroblast/mast cell signaling pathway of acupuncture

Acupuncture has been practiced for thousands of years with documented therapeutic effects, yet its underlying biological mechanisms remain poorly understood. Here, we show that acupuncture stimulation converts local mechanical forces into neuronal signals through defined cellular interactions, establishing a causal axis that links micro-level events at the ST36 acupoint to systemic therapeutic effects. We demonstrate that acupuncture needle manipulation transmits mechanical tension through collagen fibers to local fibroblasts, which subsequently secrete stem cell factor (SCF) and interleukin-33 (IL-33) in the acupoint. SCF recruits mast cells, while IL-33 induces their activation and the release of neuromodulatory molecules. These molecules then engage the nervous system, as evidenced by c-fos expression in the lumbar dorsal horn, demonstrating the transmission of acupuncture-induced peripheral signals into central circuits. Together, these findings define a functional axis linking needle-evoked stimulation to neuronal activation and provide a mechanistic framework for understanding the biological basis of acupuncture and for its evidence-based refinement.

cell biology↗

bioRxiv2025

RNA viruses in water shape the viromes of shrimp and fish in aquaculture systems

Aquatic environments host immense RNA viral diversity, yet the extent to which waterborne viruses influence the virome of aquatic animals remains unclear. Here, we conducted a comprehensive longitudinal metatranscriptomic analysis of water, shrimp, and fish across multiple culture stages in aquaculture systems. We identified 3,211 RNA viruses spanning 21 viral supergroups, with 97.4% representing novel species. Water exhibited the greatest viral diversity (3,093 species), followed by shrimp (1,280) and fish (398), with most viruses detected in shrimp and fish also detected in water. Diversity analyses revealed increasing richness and significant compositional shifts in 92 high-abundance viruses (>1,000 RPM) across culture stages. Viral abundance in aquatic animals was strongly correlated with that in water, and the temporal trajectories of the 16 most abundant viruses were closely synchronized between water and shrimp. Furthermore, 337 virus species were shared among shrimp and two fish species, of which 309 were present in water. These findings demonstrated that RNA viruses in water shape the composition and dynamics of aquatic animal viromes, underscoring the importance of water virome surveillance and management for disease prevention in shrimp aquaculture.

microbiology↗

bioRxiv2025

Class A PBPs reinforce the septal cell wall following initial synthesis by SEDS-bPBP pairs during bacterial cytokinesis

Bacterial cytokinesis requires the coordinated action of septal peptidoglycan (PG) synthases to ensure efficient and accurate septum formation. Two major types of synthases contribute: SEDS-bPBP and bifunctional class A PBPs (aPBPs). How their activities are organized in space and time has remained unclear. Using Deinococcus radiodurans, which often contains both constricting and closed septa in the same cell, we show that septal PG synthesis proceeds through distinct steps at different regions. Primary synthesis at the leading edge by SEDS-bPBP pairs drives constriction, whereas aPBPs act later at the lagging edge and in closed septa to thicken the wall, enhance cross-linking, and reinforce septal integrity. At the single-molecule level, both synthase types move directionally to perform processive PG synthesis at distinct sites. We also observed spatiotemporal separation of SEDS-bPBP and aPBP synthases in Staphylococcus aureus, suggesting that secondary septal PG synthesis is a conserved mechanism securing successful cytokinesis.

microbiology↗

bioRxiv2025

Methyl gallate Attenuates Post-Stroke Emotional and Cognitive Symptoms by Promoting Hippocampal Neurogenesis via PI3K/GSK3 and AMPK Signaling

Restoring hippocampal neurogenesis is an effective strategy for post-stroke recovery. Methyl gallate (MET) exhibits neuroprotective properties. However, the effect of MET in improving brain functional recovery in the post-stroke depression (PSD) model and its underlying mechanism remains unknown. Single-cell data analysis showed that the cell types and molecular characteristics of PSD are similar to those of primary depression but exhibit weaker synaptic plasticity and stronger inflammatory signals. In addition, molecular docking studies revealed that MET exhibits a significant binding capacity with AMPK/GSK3, suggesting that MET mediates the neuroprotective effects of both. In this study, we created a post-stroke depression (PSD) model by performing physical restraint after ischemia and tested the treatment effects of MET. We observed that MET significantly attenuated PSD-induced depressive-/anxiety-behaviors associated with a reduction of stress hormone corticosterone and ACTH levels. Morris water maze and recognition task results indicate that MET can also alleviate cognitive impairments in the PSD model. In the hippocampus of the PSD model, MET improved the proliferation and differentiation of neural stem/progenitor cells (NSPCs). MET treatment significantly enhanced the activity of AMPK and decreased the activity of GSK3{beta}. Furthermore, in primary neural progenitors under hypoxia, both the PI3K inhibitor LY294002 and the AMPK inhibitor compound C blocked the effects of MET to promote neural development. Animal experiments also confirmed that LY294002/compound C treatment could reduce the effects of MET in antidepressant behaviours. Taken together, our results indicate that PI3K, as well as AMPK-mediated adult neurogenesis, is restored by MET to improve brain functions in the PSD model.

neuroscience↗