Biology subjects

Zhang, W.

Publications and source records attributed to Zhang, W..

At least 109 records · Page 6Linked to original sources

bioRxiv2026

An Essential Role of the AMPK-Related Kinase SNRK in Regulating Drosophila Sleep

Protein kinases are important regulators of sleep in animals, but their loss-of-function mutations usually show moderate phenotypes. We report here that sucrose non-fermenting related kinase (SNRK), a member of the AMP-activated protein kinase-related kinase (ARK) family, plays an essential role in sleep regulation: Snrk gene knockout resulted in a profound loss of night-time sleep phenotype, much stronger than that of the well-known ARK member Sik3. This phenotype was completely rescued by neuronal SNRK expression. SNRK in adulthood was required for sleep. Catalytic and regulatory sites in SNRK were important for sleep. A chemoconnectomic (CCT) screen revealed SNRK functioning in cholinergic neurons whose activation is known to inhibit sleep. Sleep loss in SNRK mutants was rescued by pharmacological blockade of nicotinic acetylcholine receptors. Our findings have uncovered a fundamental role for SNRK in cholinergic neurons to regulate sleep.

neuroscience↗

bioRxiv2026

One-pot parallel Sidewinder construction from oligo pools

Reliable and cost-effective de novo DNA production at scale has become increasingly important to studying and engineering biology. Double-stranded DNA is constructed from short synthetic single-stranded DNA oligonucleotides synthesized either individually or as a pool. Oligonucleotide pools offer substantially reduced costs at the sacrifice of yield and individual oligo isolation, making efficient multiplexed DNA construction from pools a complex engineering challenge, yet one which promises to reduce cost, labor, and turnaround time if solved. Here we introduce Oligo Pool Sidewinder assembly, which enables one-pot, parallel assembly of hundreds of DNA fragments simultaneously into dozens of defined constructs with high fidelity from oligo pools. We pair a computational workflow for string-based bespoke oligo design with a set of construction rules for highly multiplexed assembly. We demonstrate recovery of individual sequences from the pool by construct-specific amplification with misconnection rates as low as 1 in 10. This high fidelity for connection enables hundreds of oligos to co-assemble in a single reaction. Further, we show universal amplification of libraries of defined target sequences in a single PCR and extend the approach through in vitro hierarchical assembly to construct a large 12.5-kilobase synthetic linear DNA product.

molecular biology↗

bioRxiv2026

Ovipositor morphology and mechanosensory divergence drive niche breadth expansion in Drosophila

Ecological niche breadth is key factor associated with adaptive radiation and speciation. For most Drosophila species, the firm surface of intact ripe fruit acts as a physical barrier to oviposition, effectively restricting them to the saprophagous resources. How species overcome such mechanical constraints at the behavioral and sensory levels, and whether doing so leads to niche breadth expansion or niche specialization, remain poorly understood. Here, using comparative behavioral assays across ten Drosophila species, we show that substrate physical hardness is a critical barrier preventing most species from exploiting ripe fruit. Among species capable of puncture oviposition, there are two distinct evolutionary strategies among Drosophila species. With its serrated ovipositor and strong preference for fresh fruit, D. suzukii represents a case of ripe-fruit specialization. In contrast, D. immigrans with the needle-like ovipositor, gains access to fresh fruit while retaining the ability to exploit decaying substrates, thereby expanding its resource niche. Thus, D. suzukii considered as the typical evolutionary niche specialization, while D. immigrans represents niche expansion. Furthermore, using the genetic toolkit of D. melanogaster, we further identify the Inactive (IAV) mechanosensory channel as important regulator of stiffness-dependent oviposition inhibition. Loss of iav reduced inhibition on firm substrates, while cross-species rescue experiments showed that IAV orthologs differed in their ability to restore this response in a common genetic background. Puncture oviposition was also associated with successful offspring development on firm fruit and with the use of firm-surfaced hosts under natural conditions. Together, these findings identified a novel niche expansion of D. immigrans among the saprophagous Drosophila.

evolutionary biology↗

bioRxiv2026

ExMODE: A Multi-Omics Repository for Extremophile Adaptation and Bioprospecting

Extreme environments, though hostile to most life forms, host specialized extremophile communities that have redefined biological cognition and emerged as vital biotechnological resources, with their unique adaptive traits and bioactive molecules driving advances in multiple scientific and industrial fields. However, research on extremophiles is hindered by limitations in culture-based methods, fragmented multi-omics data with non-uniform annotation standards across repositories, the lack of cross-extreme comparative research in existing resources, and the singularity of data dimensionality that neglects key structural information, all of which restrict the functional interpretation of extremophile microbes and the exploitation of their bioprospecting potential. To tackle these challenges, we developed ExMODE (https://db.genomics.cn/exmode/), a comprehensive multi-omics database platform dedicated to extremophiles. It centrally integrates multi-omics data from diverse extreme habitats with a standardized annotation framework, resolving data fragmentation and enabling systematic cross-environment comparative analyses to elucidate extremophile adaptive mechanisms. Moreover, ExMODE aggregates multi-dimensional datasets including genes, genomes, secondary metabolite sequences and protein structures, overcoming the constraints of single-dimensional data and significantly improving the efficiency of biotechnological resource discovery from extreme microorganisms.

microbiology↗

bioRxiv2026

An Isoform-Centric, Structure-Aware Framework for Protein Function Prediction and Evaluation, Instantiated in 3DisoDeepPF

Understanding and accurately predicting function across protein isoforms has been a long-standing challenge with profound implications for both biological and translational research. However, most functional annotations and benchmarks remain tied to genes or reference protein sequences, leaving limited support for distinguishing protein isoforms from the same gene whose sequence, structure and domain composition may lead to different functions. To address this gap, we developed an isoform-centric framework for protein function and domain annotation that integrates a dense graph of sequence and structure similarity with protein features. We implemented this framework as 3DisoDeepPF, a graph-based multimodal model, and applied it to a breast cancer isoform atlas. Across canonical benchmarks and evaluations at isoform resolution, 3DisoDeepPF showed strong performance in predicting GO terms and Pfam domains and remained robust in tests with homology control. It further captured changes in Pfam domain composition among isoforms from the same gene, including reference-relative domain gain and loss. An evidence tracing module links predicted labels to supporting proteins in the graph, as illustrated by the calcium and integrin binding protein 1 (CIB1). Together, this study provides a framework informed by protein structure for function and domain annotation at isoform resolution, converting human protein isoform diversity into traceable functional evidence for cancer atlas interpretation.

cancer biology↗

bioRxiv2026

Multi-Modal Deep Learning Integrates Spatial Topologies and Sequential Motifs to Identify Class I HDAC Inhibitors as Pan-Cancer Therapeutics

The molecular characterization of human solid tumors has introduced immense genomic complexity and intra-tumoral diversification. Converting these detailed, multi-omic profiles right into workable, broad-spectrum therapeutics continues to be an formidable bottleneck in precision oncology. Traditional computational drug repurposing strategies largely rely on single-modality chemical descriptors, which frequently fail to capture the systemic transcriptomic interactions within the highly dynamic tumor microenvironment. Here, this study presents a robust multi-modal deep learning framework that synergistically integrates two-dimensional (2D) molecular graphs via Graph Neural Networks (GNNs) and chemical functional group patterns via self-attention Transformers. By mapping this dual-stream chemical feature space to the perturbational transcriptomic signatures (LINCS L1000) of 22 distinct cancer types from The Cancer Genome Atlas (TCGA), a vast library of over 28,000 small-molecule compounds was computationally screened. The developed multi-modal architecture achieved state-of-the-art predictive accuracy, significantly outperforming traditional single-modality baseline models. Strikingly, the comprehensive pan-cancer transcriptomic reversal landscape identified a persistent convergence of non-oncology drugs exhibiting potent broad-spectrum anti-tumor potential. Specifically, Class I Histone Deacetylase (HDAC) inhibitorsmost notably TC-H-106, RG2833, and Tianeptinaline, agents originally developed to penetrate the blood-brain barrier for neurodegenerative and psychiatric disordersemerged as top therapeutic candidates across lung adenocarcinoma (LUAD), bladder urothelial carcinoma (BLCA), and rectum adenocarcinoma (READ). Subsequent high-dimensional network pharmacology and functional enrichment analyses confirmed that these agents robustly suppress essential oncogenic pathways, specifically collapsing the G1/S phase transition and DNA damage repair machineries. Furthermore, structural validation via molecular docking and force-field thermodynamics confirmed the highly stable physical binding affinity (Vina score: -7.0 kcal/mol, MMFF94 Energy: 64.76 kcal/mol) of TC-H-106 to the HDAC1 catalytic pocket. Kaplan-Meier survival analysis based on TCGA gene expression stratification underscored the significant prognostic benefit of targeting this epigenetic axis. Collectively, these findings introduce a powerful multi-modal AI framework for systems-level drug repurposing and highlight brain-penetrant Class I HDAC inhibitors as highly promising candidates for pan-cancer epigenetic therapy.

bioinformatics↗

bioRxiv2026

CellChem: Cellular transcriptional responses reshape molecular representation space for efficient and multi-scale drug discovery

Despite decades of progress in computational drug discovery, deep learning-based molecular representation models remain largely structure-centric, assuming that chemical similarity approximates functional similarity. However, drug effects in cells are shaped not only by chemical similarity but also by molecular interactions in the cellular context. To capture this complexity, we introduce CellChem, a cellular-chemical representation-learning framework that learns cell-guided molecular representations of small-molecule actions within cells. By incorporating large-scale cellular transcriptional profiles during pretraining, CellChem reshapes molecular representation space from structure-centric to a balanced integration of structure and function. The learned CellChem molecular representations exhibit biologically meaningful geometric organization, such that distances between molecules encode not only structural similarity but also similarity in the cellular responses they elicit, independent of downstream tasks. Using downstream derivative models such as cell-guided compound-protein interaction prediction and drug-induced transcriptional response profile generation, CellChem supports highly efficient, multi-scale drug discovery, achieving significantly better performance than traditional models.

molecular biology↗

bioRxiv2026

DCN1 inhibitor induces fetal hemoglobin through self-limited regulation of CUL3 neddylation

Few genetic loci are as well-characterized as the globin gene locus, and the substitution of healthy {gamma}-globin (HbF) for missing or mutated {beta}-globin (HbB) is an established therapeutic strategy for {beta}-hemoglobinopathies including sickle cell disease (SCD) and {beta}-thalassemia. Although substantial progress has been made in understanding HbF derepression and globin switching, many current therapeutic strategies involving small molecules increase HbF through broad epigenetic perturbations or cytotoxic stress, raising concerns about dose-limiting cytopenias and off-target effects. By coupling single-cell transcriptomics, genetic perturbations, and functional genomics, we identified an unknown role of neddylation in the regulation of fetal hemoglobin (HbF). Partial impairment of neddylation of cullin ubiquitin ligase 3 (CUL3) through defective in cullin neddylation 1 (DCN1) inhibition leads to highly selective chromatin changes, histone demethylation, and globin locus binding of known activators of HbF transcription. Further, DCN1 inhibition drives globin switching and HbF increases in vitro and in vivo with minimal off-target transcriptional effects and no evidence of cytotoxicity or stress erythropoiesis. To therapeutically target this axis, we report the discovery and characterization of CLY-124, a first-in-class, covalent DCN1 inhibitor with favorable pharmacology properties. In a humanized mouse model, CLY-124 showed a dose-dependent increase in HbF as monotherapy and in synergy with hydroxyurea (HU), a current standard of care. Collectively, these findings highlight the power of single-cell transcriptomics to elucidate undiscovered biologic insights with therapeutic potential, and the promise of DCN-1 inhibitors like CLY-124 to address {beta}-hemoglobinopathies. With an appropriate nonclinical safety profile, a first-in human study of safety, pharmacokinetics and HbF assessments in healthy volunteers and participants with SCD is ongoing for CLY-124. One-sentence SummaryDCN1 is a promising target for {beta}-hemoglobinopathies

molecular biology↗

bioRxiv2026

Dissecting inter-focal heterogeneity and convergent immunosuppressive ecosystems in multifocal hepatocellular carcinoma through single-cell and spatial multi-omics

Background Multifocal hepatocellular carcinoma (HCC) comprises spatially separated tumor foci with distinct evolutionary trajectories, posing a major therapeutic challenge. Whether divergent lesions retain shared immune-evasion mechanisms beyond lesion-specific heterogeneity and offer cross-focal therapeutic opportunities remains unknown. Objective To resolve malignant and microenvironmental heterogeneity across tumor foci and identify conserved immunosuppressive programs underlying multifocal HCC progression. Design Matched tumour foci and peritumoural tissues from patients with multifocal HCC underwent integrated single-cell and spatial multi-omics profiling, including scFAST-seq (n=15), scATAC-seq (n=12), and Stereo-seq (n=14). In-house RNA-seq (n=13), public scRNA-seq (HRA001748) and RNA-seq datasets (TCGA-LIHC, OEP000321) were used for validation. Multiplex immunohistochemistry (n=96) and functional assays validated key findings. Results Multifocal HCC exhibited extensive inter-focal heterogeneity in malignant genomic, transcriptional, epigenetic, and evolutionary states, accompanied by diverse immune and stromal landscapes. Despite this divergence, spatially separated tumor foci converged on shared malignant states marked by elevated TMED2 expression and conserved immunosuppressive ecosystems characterized by regulatory T-cell (Treg) and SPP1+/SPRED1+ macrophage enrichment, impaired cytotoxic CD8+ T-cell immunity, and recurrent stromal-vascular remodeling. Mechanistically, malignant hepatocytes engaged SPP1+/SPRED1+ macrophages through C3/C5 complement signaling across divergent tumor foci, while macrophages and Tregs contributed to CD8+ T-cell dysfunction through CD274-PDCD1, CD80/CD86-CTLA4/CD28, and MHC-I-CD8 interactions. A tumor-intrinsic TMED2-ADAR1-dependent A-to-I RNA editing program promoted C3/C5 complement expression and secretion, linking malignant heterogeneity to conserved tumor-immune signaling. Conclusions Despite divergent malignant evolution, multifocal HCC converges on shared immunosuppressive ecosystems. The TMED2-ADAR1-C3/C5 complement axis represents a conserved tumor-immune vulnerability that may enable therapeutic strategies targeting common immune-evasion mechanisms across heterogeneous tumor foci.

cancer biology↗

bioRxiv2026

Drosophila Arc1 is required for metabolic resilience and developmental timing during dietary challenges

Energy homeostasis at the organismal level requires balancing energy storage and mobilization to provide sufficient fuel for energy-intensive processes like development without depleting or accumulating excess stores. Fluctuations in the nutritional content of the diet present a challenge to the pathways that maintain energy balance. We previously identified the Drosophila melanogaster counterpart of human ARC (activity-regulated cytoskeleton-associated protein) as a brain-expressed protein that regulates energy storage in the major fat storage tissue of the fly, the fat body. Here we show that Arc1 expression in the brain responds to changes in diet and insulin-like peptide levels. Mutating Arc1 perturbs the ability of larvae to maintain normal body fat and rates of development upon dietary changes: mutants develop slower or faster than wild-type on nutrient-poor or nutrient-rich diets, respectively. Excess fat storage in Arc1 mutants becomes an advantage upon starvation, prolonging survival relative to the wild type. In addition to metabolic and neuronal genes, transcriptomic analysis revealed changes in key developmental drivers of development, in both diet-dependent and - independent manners. This study supports a model in which nutrient regulation of Arc1 via insulin-like peptide signaling couples dietary changes to changes in metabolism -- to maintain energy homeostasis -- and production of hormone signals, to support timely development. In this role, Arc1 is a central player in a buffering mechanism that coordinates nutrient availability, organismal metabolism, and developmental rate.

genetics↗

bioRxiv2026

N-3 Polyunsaturated Fatty Acids Ameliorate Post-infarction Cardiac Dysfunction Through Modulation Of Adiponectin-Ceramide Metabolism

BackgroundIt has been shown that n-3 polyunsaturated fatty acids (n-3 PUFA) of marine origin exert significant beneficial effects on myocardial infarction (MI); however, the underlying mechanisms remained unclear. Ceramides play a vital role in the regulation of energy metabolism, mitochondrial function, and apoptosis. Through the integration of clincial studies and animal experiments, this study aimed to determine whether n-3 PUFA improved myocardial function by modulating ceramide metabolism. MethodsIn a case-control study, 100 patients with AMI and 100 healthy pariticipants were enrolled to measure serum ceramide concentrations. Meanwhile, mice were randomly allocated into 4 groups and administrated to a 3-week intervention with n-3 PUFA in triglyceride and phospholipid forms. A mouse model of MI was then established, followed by an additional 4 weeks of continuous intervention. Subsequent comprehensive assessments of cardiac function were performed in the mice. Finally, the mice were euthanized to conduct targeted ceramide lipidomic analysis and other relevant assays. ResultsThe levels of serum C16:0-, C18:0-, C20:0-, C24:1-ceramides and total ceramides in patients with acute myocardial infarction (AMI) were significantly higher compared with the healthy controls. In the murine model of myocardial infarction, pathological analysis via TTC staining demonstrated that interventions with fish oil (triglyceride form) and krill oil (phospholipid form) both significantly reduced myocardial infarct size. Concomitant echocardiographic assessment confirmed that both treatments markedly elevated left ventricular ejection fraction (LVEF), with the magnitude of improvement being significantly superior to that of the model control group. Concurrently, compared with the model group, the concentrations of ceramides in cardiac tissue and serum were significantly lower in the groups with fish oil and krill oil intervention. Western blot analysis further confirmed that n-3 PUFA intervention upregulated adiponectin expression, reduced ceramide accumulation in myocardial tissue, and inhibited mitochondria-mediated cardiomyocyte apoptosis, thereby improving cardiac function and prognosis following myocardial infarction. ConclusionsThis work demonstrates that n-3 PUFA exert cardioprotective effects following MI mediated by adiponectin-ceramide axis. However, there is no significant difference regarding therapeutic efficacy of n-3 PUFA in triglyceride or phospholipid forms.

pharmacology and toxicology↗

bioRxiv2026

Fruit trichome density outweighs cuticle thickness as the dominant barrier to postharvest water loss in tomato

Fruit cuticle thickness and biochemical composition have traditionally been regarded as the primary determinants of postharvest water loss in fleshy fruits. However, several reports indicate that some tomato mutants with thinner fruit cuticles or less cutin and waxes do not always show increased transpiration, suggesting that additional surface features influence postharvest water loss. Here, we s how that fruit trichome density is a previously underappreciated determinant of postharvest water loss in tomatoes. Using two independent mutants, cr-slhdziv7 and cr-slhdziv9, which exhibit reduced fruit trichome density, we found that both mutants displayed reduced water loss rates and extended shelf life during postharvest storage despite having thinner cuticles and reduced levels of key cutin monomers. Further molecular analyses, including RNA-seq, yeast one-hybrid (Y1H), and dual-luciferase reporter assays, revealed that these two HD-ZIP IV proteins not only regulate fruit trichome formation but also directly or indirectly modulate the expression of multiple cutin biosynthesis genes. Collectively, our results demonstrate that the benefit of reducing trichome-associated microchannels can outweigh the negative effects of cuticle thinning on postharvest water loss. This study establishes fruit trichome density as an important and previously underestimated target for improving postharvest fruit quality and shelf life. HighlightO_LIFruit trichome density controls tomato postharvest water loss and dominates over cuticle thickness barrier. C_LIO_LILess trichomes reduce microchannels, lowering transpiration despite thin cuticles and extending tomato fruit shelf life. C_LI

plant biology↗

bioRxiv2026

MTB-KB: A Curated Knowledgebase of Mycobacterium tuberculosis Related Studies

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), has regained its position as the worlds leading killer among infectious diseases. Despite extensive research progress across epidemiology, diagnosis, drug development, treatment regimens, vaccines, drug resistance, virulence factors, and immune mechanisms, MTB-related knowledge remains fragmented across thousands of publications, limiting its effective use. To address this gap, we present MTB-KB, a literature-curated knowledgebase that systematically integrates high-impact findings from eight major sections of TB research. The current release contains 75,170 associations from 1,246 publications, covering 18,439 entities standardized using authoritative databases and WHO-endorsed classifications. A central feature is the interactive knowledge graph, which links cross-section associations to reveal and infer MTB-host interactions, treatment strategies, and vaccine development opportunities. MTB-KB also provides a user-friendly interface with browsing, advanced search, and statistical visualization. Overall, by consolidating dispersed MTB knowledge into a structured and accessible platform, MTB-KB provides a valuable resource for researchers, clinicians, and policymakers, supporting both basic and clinical TB research, enabling evidence-based TB prevention, diagnosis, and treatment, and contributing to global elimination efforts. MTB-KB is accessible at https://ngdc.cncb.ac.cn/mtbkb/.

bioinformatics↗

bioRxiv2026

STDrug enables spatially informed personalized drug repurposing from spatial transcriptomics

Drug repurposing offers a scalable route to accelerate therapeutic discovery, yet existing approaches based on single-cell RNA sequencing (scRNA-seq) often overlook spatial tissue context, limiting their ability to capture microenvironment-dependent drug responses. Here we present STDrug, a spatially informed computational framework that integrates spatial transcriptomics, graph-based modeling, and multimodal learning to enable patient-specific therapeutic prioritization. STDrug identifies and aligns disease and control spatial domains using graph convolutional networks and coherent point drift, and prioritizes candidate drugs through an integrative scoring scheme combining tumor-reversible gene signatures, perturbation-based reversal scores, and knowledge-guided gene weighting within a machine learning framework. By modeling spatial domain interactions alongside predicted drug efficacy and toxicity, STDrug generates robust patient-level drug scores. Across hepatocellular carcinoma and prostate cancer datasets, STDrug outperforms existing single-cell and spatial transcriptomics-based drug repurposing methods, achieving signficantly improved predictive accuracy (AUCs=0.81-0.82) across patients. Validation using large-scale electronic health records and in vitro assays further supports the translational relevance of top-ranked candidates. Taking together, STDrug establishes a generalizable framework for incorporating spatial omics into therapeutic discovery, advancing spatially informed and personalized drug repurposing.

bioinformatics↗

bioRxiv2026

Interactive Effects of Biological Maturation and Relative Age Effect on Talent Identification for U16 Elite Soccer Players

This retrospective study aims to explore the interactive effects of biological maturation and relative age effect (RAE) on talent identification. 56 male elite soccer players matched for chronological age (15.08{+/-}0.41 years) were studied. Test items included anthropometry (height, body mass, sitting height, leg length, BMI and Quetelet index), physiology (power, speed, agility, speed endurance and aerobic performance), soccer-specific skills (passing, shooting and dribbling), psychology (achievement motivation, orientation and resilience) and biological maturation (APHV) tests. The test results were analyzed independent sample t-test, Pearson correlation analysis, and stratified regression. Conclusion: Biological maturation significantly influences anthropometry (height, weight and Quetelet index), lower limb explosive, and speed (single-leg jump, standing triple jump, and 30-m sprint) in U16 male elite soccer players in Shanghai. The relative age effect shows no significant impact on talent selection indicators, which is attributed to the accumulated training load effect. The mechanisms of biological maturation and RAE in youth soccer talent selection are distinct and operate independently.

developmental biology↗

bioRxiv2026

Osmotic pressure gradients in E. coli biofilms revealed by in-situ sensors

Osmotic pressure has been known to play essential roles in living systems from single cells to complex tissues. However, direct in-situ measurements of osmotic pressures in biosystems have remained challenging, especially in complicated heterogeneous systems in which osmotic pressure gradients could exist and induce directed forces. Bacterial biofilms -- organized communities of bacteria encased in a self-produced extracellular matrix -- are a major mode of bacterial life. It has, however, remained unexplored how the osmotic pressure is distributed in the biofilm and how this distribution contributes to biofilm growth and activity. Here, liposomal nano-sensors are developed for the in-situ mapping of osmotic pressures at an unprecedented microscale resolution in real time using Escherichia coli. biofilm as a model system that develops at the surface of a hydrogel containing the nutrients. The measurements reveal osmotic pressure gradients with a radially increasing trend from the inner regions to the outer regions of the biofilm, which is associated with biofilm formation, morphology, and metabolism. The gradients likely contribute to mechanical properties, internal stresses, and nutrient transport. The sensor readouts also show that there is an osmotic pressure difference between the biofilm and the adjacent medium, which may promote biofilm expansion through matrix swelling and bacteria growth via water and nutrient uptake from the surroundings. Our novel approach based on in-situ osmotic pressure mapping in a growing biofilm reveals a sophisticated spatial regulation of physical forces, which may inspire new models and approaches in the field of mechanobiology.

biophysics↗

bioRxiv2026

Probiotic Lactiplantibacillus plantarum VB165 improves metabolic disorders in Insulin-Resistant Mice

This study investigated the effects of Lactiplantibacillus plantarum VB165, a probiotic strain with intrinsic -glucosidase inhibitor (AGI) activity, on metabolic disorders in high-fat diet (HFD)-induced insulin-resistant (IR) mice. Male C57BL/6 mice were divided into four groups: normal control diet (NCD), NCD supplemented with VB165, HFD, and HFD supplemented with VB165. After 16 weeks, VB165 supplementation significantly attenuated HFD-induced weight gain and reduced epididymal and inguinal white adipose tissue indices. VB165 also improved glucose intolerance and insulin resistance (IR), as demonstrated by oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT), and lowered fasting blood glucose, fasting insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) levels. Additionally, it ameliorated dyslipidemia by reducing serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), while alleviating hepatic steatosis and adipocyte hypertrophy. Mechanistically, VB165 enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1 and Occludin), reduced systemic inflammation by lowering LPS, IL-6, and IL-1{beta}. Gut microbiota analysis revealed that VB165 modulated community composition, suppressing HFD-enriched genera (e.g., Ileibacterium and Coriobacteriaceae_UCG_002) and promoting beneficial taxa (e.g., Faecalibaculum and Oscillibacter). These findings demonstrate that L. plantarum VB165 improves HFD-induced metabolic disorders via multi-target mechanisms, highlighting its potential as a probiotic intervention for IR and related metabolic diseases.

microbiology↗

bioRxiv2026

Beyond Acoustic Cues: Olfactory-Mediated Avoidance of Bats by Crickets

The evolutionary arms race between insectivorous bats and their insect prey is a classic paradigm of acoustic predation and evasion, with insects having evolved sophisticated auditory countermeasures. Both bats and insects also rely heavily on olfaction for key behaviors, such as social communication. Moreover, predator-derived odors are well-established as risk cues in many other predator-prey systems. However, whether olfaction plays a role in the bat-insect arms race remains unknown. Here, we unveil a previously unknown olfactory dimension to this interaction. We demonstrated that the body odor of the insectivorous bat Scotophilus kuhlii triggered robust avoidance and electrophysiological antennal responses in a common cricket prey, Loxoblemmus equestris. We identified limonene as a behaviorally active volatile in bat odor that elicited electrophysiological responses in cricket antennae and was sufficient to elicit avoidance in crickets. Field experiments confirmed that limonene exposure reduced cricket calling activity, demonstrating the ecological relevance of this cue. Our findings establish that insects can detect and initiate avoidance of phylogenetically distant vertebrate predators via olfaction, a process that could be mediated by the elemental perception of individual odor compounds. This work broadens the sensory framework of a classic predator-prey system, and highlights olfactory eavesdropping as a functional strategy in phylogenetically distant predator-prey systems.

ecology↗