Biology subjects

Wang, M.

Publications and source records attributed to Wang, M..

At least 127 records · Page 7Linked to original sources

bioRxiv2026

Combined Antibiotic and Herbicide Pollution Accelerates the Horizontal Transfer of Antibiotic Resistance Genes in Coastal Microbial Communities

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/708170v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@4c2513org.highwire.dtl.DTLVardef@116256corg.highwire.dtl.DTLVardef@f30846org.highwire.dtl.DTLVardef@1a44e00_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG The extensive use of herbicides and antibiotics in aquaculture has led to compounded pollution of coastal waters, marked by the co-occurrence of herbicides, antibiotic residues, and antibiotic resistance genes (ARGs). Plasmid-mediated conjugative transfer is a major driver of the dissemination and evolution of ARGs, yet the influence of herbicides alone or in combination with antibiotics on this process in aquatic bacterial communities remains unclear. In this study, we demonstrated that triazine herbicides, alone and in combination with a fluoroquinolone antibiotic, significantly promote the conjugative transfer of the broad-host-range RP4 plasmid. Using Escherichia coli DH5 as a donor, we observed increased plasmid transfer to multiple recipients, including E. coli HB101, Pseudomonas putida KT2440, and a natural coastal seawater microbial community. The enhanced transfer under co-exposure was associated with several interacting mechanisms, including elevated intracellular reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels, increased cell membrane permeability, altered extracellular polymeric substance (EPS) composition, and upregulated expression of conjugation-related genes. Overall, this work underscores the potential role of combined herbicide and antibiotic contamination in shaping the microbial resistome of coastal ecosystems and provides insights to inform strategies for mitigating the spread of antibiotic resistance.

microbiology↗

bioRxiv2026

What microbes want: exploring microbial substrate preferences with the Web of Microbes Agent

Understanding and predicting bacterial substrate preferences has broad utility from microbial interactions to selecting prebiotics. Isolate exometabolite profiling directly measures which compounds a given microbe utilizes from an array of metabolites in the environment. However, modeling, mining, and integrating these data are challenging. Here, we introduce a Bayesian Personalized Ranking (BPR) model applied to substrate preferences which we find learns to rank compounds by a given microbes preference. It was found to outperform the other ranking models (AUC = 0.93), proved robust to ablation, showed strong within-genus isolate pairs correlation (Spearman rank = 0.78) and predictive ability for new data. BPR was then used to create the Web of Microbes (WoM) Agent by integrating it with the Phydon growth model and Large Language Model (LLM) for autonomous orchestration tool calling and analysis. The WoM Agent accurately predicted substrate consumption by existing strain grown on a novel medium and correctly identified bacteria enriched in soil metabolite spike-in experiments. Additionally, the WoM Agent can use autonomous reasoning including to predict substrates that will selectively promote the growth of one clade of bacteria over another including helping interpret results and suggest new hypotheses and experiments. We anticipate broad applications in microbial cultivation, microbiome engineering, and environmental microbiology, with the agents capabilities further extensible through the integration of additional tools and use of rapidly improving LLMs.

systems biology↗

bioRxiv2026

A specialized ARGONAUTE enables trans-species RNA interference in plant immunity

Trans-species RNA interference (tsRNAi), in which plants produce small RNAs (sRNAs) to silence target genes in pathogens, has emerged as a promising strategy for disease control. However, whether tsRNAi constitutes an endogenous, regulated immune response remains unclear. Here, we show that ARGONAUTE10 (AGO10) plays a critical role in pathogen-induced tsRNAi. Loss of AGO10 in Arabidopsis abolished pathogen gene silencing during infection, leading to hypersusceptibility to oomycete and fungal pathogens. Importantly, AGO10 rapidly responds to pathogen infection through increased protein accumulation and re-location into discrete cytoplasmic condensates, thus promoting the production of trans-species sRNAs at the pathogen infection sites. This immune responsiveness relies on the N terminal intrinsically disordered region (IDR) of AGO10, which is responsible for sensing and responding to immune activation. Specific features in the IDR partitions AGO10 into two deeply diverged subgroups, AGO10a and AGO10b, with the immune responsiveness and defense function evolutionarily conserved in AGO10a but not AGO10b. Together, these findings establish tsRNAi as a bona fide, evolutionarily conserved immune response and position AGO10 as a signal-responsive hub linking pathogen perception to tsRNAi-based defense.

plant biology↗

bioRxiv2026

Navigating the conjugated metabolome

Lifes chemical diversity far exceeds current biochemical maps. While metabolomics has catalogued tens of thousands of small molecules, conjugated metabolites, formed when two or more molecular entities are covalently fused through amidation, esterification, or related chemistries, remain underexplored. These molecules can act as microbial signals, detoxification intermediates, or endogenous regulators. Here, we mined 1.32 billion MS/MS spectra across public metabolomics repositories using reverse spectral searching coupled with delta-mass inference to map conjugation events. We generated structural hypotheses for 24,227,439 MS/MS clusters. From these, we inferred 217,291 substructure pairs with dual spectral support and 3,412,720 candidate conjugates with single-match support. Predictions span host-microbe co-metabolites, diet-derived conjugates, and drug-derived species, including drug-ethanolamine and creatinine conjugates with altered bioactivities. We also uncover a family of steroid-phosphoethanolamine conjugates. Fifty-five conjugates were matched by MS/MS of synthetic standards for this work, with 27 additionally supported by retention time matching in biological samples. Guidance on how to leverage this resource is also provided. Together, these results deliver a pan-repository map of potential conjugation chemistry, establish a resource for structural discovery and MS/MS annotation, and offer a scalable framework to explore the scope and diversity of the conjugated metabolome.

bioinformatics↗

bioRxiv2026

Lacticaseibacillus rhamnosus GR-1 attenuates Escherichia coli-induced endometritis in mice, accompanied by modulation of uterine microbiota and metabolite profiles

ObjectiveEndometritis in dairy cows is a highly prevalent infectious disease in cattle farming, which can cause persistent inflammatory responses in the uterus. This study aimed to evaluate the therapeutic efficacy of Lacticaseibacillus rhamnosus (L. rhamnosus) GR-1 against Escherichia coli (E. coli)-induced endometritis in mice and investigate its regulatory effects on uterine microbiota and metabolites. MethodsA total of 36 female BALB/c mice aged 7-8 weeks were randomly divided into 4 groups: CONT group, ECOL group (1.0x108 CFU/mL E. coli), AMP group (0.1 mg/kg ampicillin), and GR-1 group (1.0x109 CFU/mL L. rhamnosus GR-1). Uterine morphological characteristics were observed, and the expression of uterine inflammatory cytokines, oxidative apoptosis-related genes and proteins, as well as related reproductive indices were detected. 16S rRNA sequencing and metabolomic sequencing were performed to evaluate the profiles of uterine microbiota and metabolites. ResultsL. rhamnosus GR-1 effectively alleviated E. coli-induced uterine edema and inflammatory infiltration, and modulated the levels of inflammatory factors (MPO, IL-6, IL-1{beta}, TNF-, IL-10 and MDA) in the uterus. Meanwhile, this strain elevated the levels of antioxidant factors (GSH-Px and SOD), inhibited the expression of the oxidative apoptosis-related factors Keap1, Bax and caspase-3, and upregulated that of Nrf2, HO-1, NQO1 and Bcl-2. Furthermore, treatment with L. rhamnosus GR-1 increased the abundance of beneficial uterine microbiota, promoted the accumulation of L-isoleucyl-L-proline and N-acetylcysteine, and ameliorated the pregnancy status of mice. ConclusionL. rhamnosus GR-1 enhanced uterine anti-inflammatory and antioxidant stress capacity to alleviate E. coli-induced endometritis in mice. It modulated uterine microbiota and metabolites, and also improved the reproductive capacity of mice. Thus it may provide a potential antibiotic alternative for the treatment of dairy cow endometritis.

microbiology↗

bioRxiv2026

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

bioRxiv2026

Joint Modeling of Transcriptomic and Morphological Phenotypes for Generative Molecular Design

BackgroundEffectively translating data on complex cellular responses from transcriptomic and morphological measurements into molecular design remains a significant computational challenge. Existing generative methods operate on single modalities and condition on post-treatment measurements without leveraging paired control-treatment dynamics to capture perturbation effects. ResultsWe present Pert2Mol, a framework for multi-modal phenotype-to-structure generation that integrates transcriptomic and morphological features from paired control-treatment experiments. Pert2Mol employs bidirectional cross-attention between control and treatment states to capture perturbation dynamics, conditioning a rectified flow transformer that generates molecular structures along straight-line trajectories. We introduce Student-Teacher Self-Representation (SERE) learning to stabilize training in high-dimensional multi-modal spaces. On the Ginkgo Data Platform (GDP) dataset, Pert2Mol achieves Frechet ChemNet Distance of 4.996 compared to 7.343 for diffusion baselines and 59.114 for transcriptomics-only methods, while maintaining perfect molecular validity and appropriate physicochemical property distributions. The model demonstrates 84.7% scaffold diversity and 12.4 times faster generation than diffusion approaches with deterministic sampling suitable for hypothesis-driven validation. ConclusionsPert2Mol establishes a new paradigm for linking high-content phenotypic screening data with computational hypothesis generation in drug discovery: joint multi-modal perturbation modeling enables more accurate and structurally diverse molecular design than single-modality or diffusion-based approaches. Code and pretrained models are available at https://github.com/wangmengbo/Pert2Mol.

bioinformatics↗

bioRxiv2026

Generating Joint Transcriptomic and Morphological Responses to Drug Perturbations via Rectified Flow

MotivationPredicting cellular responses to drug perturbations requires capturing complex dependencies between transcriptomic and morphological changes. Existing approaches model these modalities in isolation, missing critical molecular-phenotypic relationships that occur simultaneously during drug treatment. No current method jointly predicts gene expression profiles and cellular morphology from chemical perturbations. ResultsWe introduce PertFlow, a unified computational frame-work that simultaneously predicts treatment gene expression (bulk RNA-seq) and generates cellular morphology (Cell Painting images) from control cellular states, conditioned on drug metadata. Evaluated on paired RNA-seq and imaging data from 3 cell lines and 40 compounds (17,242 samples), PertFlow achieves Pearson correlation of 0.780{+/-}0.264 for transcriptomic prediction and FID of 24.06 for morphological generation. Board-certified pathologists rated generated images with median similarity scores of 7.11-7.89/10. The model successfully recovers known drug mechanisms including microtubule disruption, DNA damage, and MAPK pathway inhibition, with gene enrichment analysis confirming activation of expected biological pathways (EMT, p53, apoptosis). AvailabilityCode and pretrained models will be available at https://github.com/wangmengbo/PertFlow.

bioinformatics↗

bioRxiv2026

Cell confinement initiates a delayed but heritable loss of chromosomes

Heritable genetic changes continually arise in cancer, especially in solid tumors where cells sometimes appear compressed. Rare heritable losses of chromosomes in live cells are quantified here with chromosome reporters (ChReporters) that reveal similar levels of loss after imposing a threshold level of confinement. Compression to [~]60% of interphase height ruptures few nuclei compared to deeper compression but perturbs mitotic spindles and prolongs pro/metaphase. Chromosome mis-segregation into micronuclei is discovered only after release from modest confinement, but arrest and death predominate. All such effects are phenocopied by Nocodazole washout that generates a memory of prolonged mitosis, and effects differ from the rapid induction of micronuclei by a spindle assembly checkpoint inhibitor and by a clinical CDK4/6-inhibitor of cell cycle entry. Single-cell-RNA-sequencing confirms chromosome loss days after confinement and reveals persistence of chromosome segregation pathways. Chromosome losses as mitotic memories of confinement ultimately address knowledge gaps in mechanobiology and cancer evolution.

cell biology↗

bioRxiv2026

A Functional Metabolomics Framework to Track Microbiome Drug Metabolism

Understanding how gut microbes transform drugs, and how this influences microbiome composition and function, remains a key question to better understand the efficacy and side effects of pharmaceuticals. To accelerate the discovery of microbiome-derived drug metabolites, we developed a functional metabolomics workflow that combines the use of synthetic microbial communities (SynComs) with a time-series resolved molecular networking approach and advanced computational metabolite annotation. We demonstrate how this framework can be used to illuminate chemical transformation dynamics in a gut SynCom (Com20) with 50 clinical drugs. Our results highlight a multitude of drug metabolites, including multi-step metabolic cascades, some of which correlated to shifts in microbial taxa, suggesting functional links between microbiome composition and biochemical transformations. Our computational data analysis workflow is publicly available through the GNPS2 ecosystem at chemprop.gnps2.org, which can be used to prioritize biotransformations and other (bio)chemical reactions in various biological and abiotic systems.

systems biology↗

bioRxiv2026

Evolutionary genomics of local adaptation, climate vulnerability, and linarin metabolism in Opisthopappus longilobus

Global climate change and human activities are posing substantial threats to biodiversity. The genus Opisthopappus (O. taihangensis and O. longilobus), endemic to Chinas Taihang Mountains, possesses great ecological, ornamental and medicinal value. However, it is confronted with the pressures of habitat fragmentation and climate change. Here, we present the first haplotype-resolved, chromosome-scale genome assembly of O. longilobus ([~]2.95 Gb) and re-sequence 115 individuals across its range. Comparative analyses show Opisthopappus is sister to Artemisia-Chrysanthemum, with Opisthopappus and Chrysanthemum diverging at 5.15-5.18 million years ago. A profound genetic divergence is evident between O. taihangensis and O. longilobus, resulting in two distinct lineages within each species, driven by geography and climate. Our analyses indicate restricted gene flow, low diversity, and recurrent demographic bottlenecks collectively contribute to their endangerment. By integrating population genomics and environmental variables, we identified 4,437 core adaptive genes linked to water deprivation, and metabolism. Genomic offset predicts higher maladaptation risk in populations under drastic climate change. Furthermore, diverged promoters of two O-methyltransferase genes, OMT250 and OMT310, likely underlie the differential acacetin/linarin accumulation between C. morifolium and O. longilobus. These findings advance understanding of Opisthopappus evolution and climate vulnerability, offering a model for genomics-guided biodiversity conservation.

plant biology↗

bioRxiv2026

Decoding the cell intrinsic and extrinsic roles of PRC2 in early embryogenesis

Early embryogenesis is accompanied by dynamic epigenetic modifications. While such dynamics are important in cell intrinsic regulation of gene expression, their extrinsic roles in mediating intercellular communication during early embryogenesis is less understood. Using the dTAG system, here we reveal previously underappreciated stage-specific functions of PRC2 in regulating pre-implantation and primordial germ cell (PGC) development. We demonstrate that PRC2 plays important roles in regulating maternal to zygotic transition (MZT), and epiblast (EPI) formation. By systematically analyzing H3K27me3 and H3K4me3 dynamics, we redefine the timing of bivalency establishment and uncover a stepwise mechanism governing bivalency acquisition in early embryogenesis. Moreover, PRC2 regulates proper PGC numbers in the EPI by controlling Esrrb expression in the extraembryonic ectoderm (ExE). Thus, our study uncovers a previously unknown cell-autonomous function of PRC2 in preimplantation development and its non-cell-autonomous impact in PGC number regulation, both through interplays between epigenetic-epigenetic and epigenetic-TFs networks.

developmental biology↗

bioRxiv2026

Engineered probiotics that sequester arsensite in a mouse gastrointestinal system

Chronic exposure to inorganic arsenic remains a major global health concern, as arsenite is frequently present in contaminated food and drinking water and readily absorbed through the gastrointestinal (GI) tract. Once internalized, arsenite accumulates in tissues and contributes to long-term health effects, including cancer, organ dysfunction, and neurological disorders. Despite extensive efforts to reduce environmental contamination, there are currently no practical strategies to prevent dietary arsenite from entering the human body during digestion. Here, we report a synthetic biology-based approach that uses engineered probiotics to detect and sequester arsenite directly within the GI tract before systemic absorption occurs. We engineered Escherichia coli Nissle 1917 (EcN), a probiotic strain, to function as a living arsenite-interception system. Central to this design is an arsenite-responsive genetic toggle switch that activates chelator expression upon exposure and sustains production under biostatic conditions, while automatically shutting off during active cell division to limit metabolic burden and enhance biosafety. In parallel, we engineered an arsenite-binding protein derived from the transcriptional regulator ArsR to eliminate DNA-binding activity while retaining high-affinity metal binding, yielding a non-toxic chelator suitable for intracellular sequestration. The resulting engineered strain efficiently removed arsenite from its surrounding environment in vitro while maintaining robust cell viability and growth. To translate these findings to an in vivo context, we developed a mass-transfer model describing arsenite distribution among the stomach lumen, engineered bacteria, and epithelial cells. This model guided the selection of a bacterial dose predicted to substantially deplete lumenal arsenite prior to epithelial uptake. Using this strategy, we demonstrated in a mouse GI model that oral administration of engineered EcN markedly reduced arsenite entry into the bloodstream compared with wild-type EcN or no-bacteria controls. Together, these results establish a programmable probiotic platform for intercepting dietary arsenite and highlight a potential strategy for preventing absorption of environmental toxicants using living microbial therapeutics.

synthetic biology↗

bioRxiv2026

THIK-1 channel mediates microglial glucose sensing and modulates AgRP neurons

Microglia play essential roles in maintaining energy homeostasis, and their dysfunction contributes to metabolic disease. Although high-fat diet (HFD) exposure induces microglial activation, the underlying mechanisms remain poorly defined. Here, we identified a previously unrecognized role for THIK-1 channel in mediating glucose sensing of microglia in arcuate nucleus of the hypothalamus (ARH), during HFD-induced obesity. Pharmacological inhibition of THIK-1 channel with tetrapentylammonium (TPA) suppresses feeding and attenuates body-weight gain in diet induced obese mice. Mechanistically, inhibition of agouti-related peptide (AgRP) neurons is indispensable for TPA-induced hypophagia. Moreover, THIK-1 inhibition promotes microglial phagocytosis of perineuronal nets (PNNs), leading to reduced AgRP neuronal activity and feeding suppression. Together, these findings establish THIK-1 as a critical glucose sensor in hypothalamic microglia and uncover a microglia-dependent pathway through which overnutrition modulates AgRP neuronal activity via PNN remodeling to regulate energy balance, highlighting THIK-1 as a potential therapeutic target for treatment of diet-induced obesity.

neuroscience↗

bioRxiv2026

Monitoring Gene Expression in Retina with Synthetic Serum Markers

Gene expression underlies retinal development, function, and pathogenesis. However, monitoring retinal gene expression in vivo is challenging. In this study, we apply synthetic serum markers, called Released Markers of Activity, or RMAs, to quantify gene expression in an intact retina through a simple blood test. We show that RMAs can quantify transduction of multiple retinal cell-types and monitor cell implantation or cell loss. We found RMAs are sensitive enough to measure transduction of rare cell populations, such as retinal ganglion cells and could detect transplantation of as few as 100 stem cells. Expression of RMAs showed no evidence of cell loss or immune activation in the retina. Overall, these findings demonstrate that RMAs are highly sensitive, tissue non-destructive gene expression reporters that can continuously track gene delivery and cell survival in intact retina through a simple blood test.

bioengineering↗

bioRxiv2026

Fusion gene discovery in single cells from high throughput long read single cell transcriptomes

High throughput long-read single cell RNA sequencing allows for fusion gene discovery in thousands of cells in parallel, which is however constrained by the lack of robust computational tools. Here, we develop LongFUSE that employs the XOR logic operation and stringent filtering criteria for the accurate detection of cell-specific fusion genes and their splicing isoforms. LongFUSE outperforms existing tools in both simulation and real data, demonstrating high accuracy and robustness.

bioinformatics↗

bioRxiv2026

Hypatia: a set of quantitative methods for profiling isoform across cell populations

High-throughput long-read single-cell RNA-sequencing enables isoform-level study across single cells, yet methods for systematically assessing cell-to-cell variations remain limited. Here, we develop Hypatia, a comprehensive platform for dissecting isoform complexities across cell populations, devising Tsallis entropy and Cramers V to facilitate robust comparative profiling. Hypatia revealed prominent isoform species variations and usage shifts across cell-types in glioblastoma, renal cell carcinoma, and heart, highlighting clinically relevant applications for studying isoform-derived, cell-specific functions.

bioinformatics↗

bioRxiv2026

Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway

Most mammals consume small and frequent meals. By contrast, pythons are ambush predators that exhibit extreme feeding and fasting patterns and provide a unique model for uncovering molecular mediators of the postprandial response1-3. Using untargeted metabolomics, here we show that circulating levels of the metabolite para-tyramine-O-sulfate (pTOS) are increased >1,000-fold in pythons after a single meal. In pythons, pTOS production occurs in a microbiome-dependent manner via sequential decarboxylation and sulfation of dietary tyrosine. In both pythons and mice, pTOS administration activates a neural population in the ventromedial hypothalamus (VMH). In mice, these VMH neurons are required for the anorexigenic effects of pTOS. Chronic administration of pTOS to diet-induced obese male mice suppresses food intake and body weight. pTOS is also present in human blood, where its levels are increased after a meal. Together, these data uncover a conserved postprandial anorexigenic metabolite that links nutrient intake to energy balance.

physiology↗