Biology subjects

Zhu, K.

Publications and source records attributed to Zhu, K..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Sex-Specific Vulnerability to Radiofrequency Electromagnetic Radiation-Induced Reproductive and Neurological Impairment in Mice

Electromagnetic radiation (EMR) constitutes a pervasive environmental stressor, yet the sex-specific vulnerabilities to its biological effects remain inadequately characterized. This study investigated the differential impacts of 3.2 GHz pulsed EMR on reproductive and neurological functions in male and female mice following a four-week exposure regimen. We identified a pronounced sexual dimorphism in systemic and organ-specific responses. Male mice exhibited a primary vulnerability in the reproductive axis, manifesting as severe spermatogenic impairment, including depletion of the spermatogonial stem cell pool, disruption of sperm chromatin remodeling, and consequent declines in sperm quality and quantity. In contrast, exposed females showed preserved ovarian function but displayed marked neurobehavioral deficits, including increased anxiety- and depressive-like behaviors, and cognitive impairment, which were correlated with neurodegeneration in the hippocampus and prefrontal cortex. Proteomic analyses revealed distinct sex-specific biomarker profiles, with serum levels of Mdk, histone H1 variants (H1-1, H1-4, H1-5), Hp1bp3, Ncf2, and Rhoc strongly associated with male testicular dysfunction, while decreased levels of the synaptic motor protein KIF13A in serum and brain tissue were linked to female neurological impairment. Our findings delineate clear sex-divergent pathological pathways that target male spermatogenesis and female neurocognitive function and propose novel circulating protein biomarkers. This work provides a critical foundation for sex-aware risk assessment and the development of targeted preventive strategies against EMR-associated health risks.

pathology↗

bioRxiv2026

Eubiota: Modular Agentic AI for Autonomous Discovery in the Gut Microbiome

The gut microbiome regulates many aspects of human biology, including immunity and inflammatory diseases, yet mechanistic discovery and translation remain constrained by fragmented workflows and manual hypothesis integration. Here, we present Eubiota, an open-source modular agentic framework that decomposes microbiome inquiry using specialized agents for planning, execution, verification, and grounded synthesis. Coordinated through shared memory and domain-specific tools, Eubiota employs reinforcement learning to optimize multi-turn reasoning, achieving 87.7% benchmark accuracy and outperforming GPT-5.1 by 10.4%. Across four case studies, Eubiota enabled end-to-end discovery with experimental validation. Screening nearly 2,000 bacterial genes, Eubiota identified the uvr-ruv DNA repair axis as a fitness determinant under inflammatory stress, validated using transposon mutants and IBD metagenomes. It further designed a four-strain consortium that attenuated colitis severity in mice and generated a commensal-sparing antibiotic cocktail, demonstrating its utility in addressing community-level design challenges at cellular and molecular levels. Finally, Eubiota discovered diet-associated metabolites that suppress NF-{kappa}B signaling. Together, these results establish Eubiota as a scalable, tool-grounded scientific copilot for mechanistically driven microbiome discovery.

bioinformatics↗

bioRxiv2026

Large language models unlock the ecology of species interactions

Species interactions shape population dynamics, geographic distributions, evolutionary trajectories, and responses to environmental change. Yet data on these interactions remain scarce across broad spatial, temporal, and taxonomic scales because they are difficult to collect in the field. One promising source of interaction data is citizen science platforms, which contain billions of biodiversity observations, often accompanied by unstructured text comments that may document interactions among organisms. Advances in large language models (LLMs) make it increasingly feasible to identify, extract, and categorize biotic interactions from these unstructured data at scale. Here, we present an LLM workflow that collects species interaction observations from multilingual citizen science comments. Using two case studies--bird-bird and plant-pollinator interactions--we show that LLMs can rapidly extract interaction types and participating species with high accuracy. These data can greatly expand the spatial, temporal, and taxonomic coverage and resolution of species interactions data, enable new tests of long-standing ecological questions, and improve our ability to track ecological changes. With appropriate validation, expert review, and attention to data privacy for both users and sensitive species, this approach opens new opportunities to characterize, forecast, and conserve biodiversity under global change.

ecology↗

bioRxiv2025

Abundance redistribution increases predator-prey interaction potentials among North American birds

Species are dramatically shifting their geographical ranges, yet the consequences of these spatial redistributions on species interactions have not been examined at broad spatial and temporal scales. Here, we investigate how the redistribution of species abundance over the past 50 years affects the potential for predator-prey interactions among North American birds. We first predict potential predator-prey interactions based on existing data and functional traits, then construct a novel, abundance-weighted metric of interaction potential for each pair of predator and prey in local communities. Across North America, the potential for predator-prey interactions has been increasing over time. We further show that this widespread increasing trend in interaction potentials is mostly driven by higher abundances of predator species. The spatial redistributions of predators and prey lead to turnover of interactions within local communities, and the turnover is less associated with changes in climate but more associated with human-induced land use changes. Our novel approach and results highlight the importance of considering traits, abundance, and species interactions--including known and potential interactions--when studying the ecological consequences of species range shifts.

ecology↗

bioRxiv2025

Warming makes 20 boreal species grow earlier but not always taller

Climate warming is altering the timing of seasonal growth in cold-temperate and boreal ecosystems, with potential consequences for forests on multiple continents. It has been hypothesized that in a warming climate, earlier growth in spring might lead to a longer growing season and thus higher annual total growth. However, whether the period of active growth is longer in a warming climate is unclear, as is whether changes in growth rate might reinforce or offset the effect of changing growing season length in modulating annual total growth. Understanding responses in growth to warming is crucial to projecting forest dynamics under future climate change. To address this, we experimentally warmed (by +1.62 and 3.26 {degrees}C on average) open-air southern boreal forest plots for 14 years (2010 to 2023) and measured juvenile height growth from spring until fall for 20 tree and shrub species, with a total of 11,565 individual-year growth trajectories. Across all species and in various canopy (open, closed) and rainfall (ambient, reduced) contexts, experimental warming consistently advanced the timing of height growth (4.32 days per 3 {degrees}C warming). However, species differed in their annual total growth responses. Evergreen gymnosperms such as spruce, fir, and pine tended to exhibit suppressed annual total growth under warming (-15.8% per 3 {degrees}C warming), driven by a shorter duration of active growth, despite an earlier start, with little change in relative growth rate. In contrast, deciduous angiosperms and non-native shrubs often show enhanced annual total growth under warming (19.3 and 37.4% per 3 {degrees}C warming), driven by faster rate, longer duration, or a combination of both. More broadly, species with a more conservative lifestyle responded less positively in the duration and rate of growth, thus placing them at a disadvantage under warming. These contrasting responses challenge assumptions that an earlier start of the growing season universally enhances growth and highlight how warming may shift both the timing and pace of growth and thus alter community composition within mixed-species forests.

ecology↗

bioRxiv2025

Fork Reversal Safeguards Epigenetic Inheritance during DNA Replication Under Stress

During DNA replication, epigenetic information carried by histone modifications is faithfully propagated and re-established on sister chromatids, ensuring cell identity. Chromatin reassembly is tightly coupled to DNA replication, therefore whether and how perturbations to DNA replication affects the fidelity of epigenetic inheritance remain poorly understood. In this study, we reveal a critical role for replication fork reversal in maintaining the transmission of epigenetic information under replication stress. We identify that cells defective in fork reversal exhibit reduced nucleosome density at replication forks, accompanied by the loss of parental histones during their transfer onto nascent DNA. Mechanistically, we demonstrate that PrimPol activation leads to single-stranded DNA gaps in fork reversal deficient cells, and that subsequent PARylation (poly ADP-ribosylation) and DNA-protein crosslinking on these gaps evicts nucleosomes. Our findings demonstrate that replication fork reversal, a widespread physiological process, is not only essential for preserving genome integrity but also for safeguarding epigenetic stability.

biochemistry↗

bioRxiv2025

Dominance of plasticity in wind-pollinated trees' flowering time response to temperature

Climate change is shifting the flowering phenology of wind-pollinated trees, leading to longer pollen seasons and heightened allergy risks. Accurately forecasting these phenological shifts requires a clear understanding of the underlying mechanisms and variations in the sensitivity of phenology to temperature. Here, we investigated the temperature sensitivity of flowering phenology in 74 wind-pollinated tree species across the US using long-term herbarium records spanning over a century. We found consistent phenological responses to spring temperature variations over space and over time in 77% of species, indicating that these long-lived trees can rely primarily on plasticity to cope with temperature variation across different regions. Sensitivity estimates were consistent across both century-scale and decadal time scales, challenging the previous understanding of declines. Interspecific variations in sensitivity exhibited a strong phylogenetic signal, indicating evolutionary conservatism in phenological responses among related species. Together, these findings shed light on the magnitude, mechanism, trend, and variability of temperature sensitivity of wind-pollinated tree flowering phenology. Our results improve the mechanistic basis for forecasting phenological shifts and their downstream effects on airborne pollen and allergen exposure under ongoing climate change.

ecology↗

bioRxiv2025

Accelerated biomass loss in western US forestlands due to shifting fire regime

Wildfires influence the distribution of biomass across the Earths surface and drive losses of carbon from the land surface to the atmosphere. Although the global budget between terrestrial and atmospheric carbon pools is comparatively well understood (Jones et al., 2024; MacCarthy et al., 2024), the growing size and severity of wildfires present an increasing challenge to regional carbon accounting. To quantify vegetation biomass across arid systems in the western US, we used remote sensing data to estimate the aboveground live biomass density (Mg ha-1) at 30-meter resolution across the states of Utah and Nevada annually from 2000 to 2022. Time series biomass maps showed accelerated loss of terrestrial carbon to the atmosphere as a result of increasing wildfire, with annual biomass burnt increasing at 0.105 {+/-} 0.024 Mt yr-1 (mean {+/-} standard deviation) after 2015. Recent shifts in the wildfire regime show a transition from predominantly early-season fires in low-biomass grasses and shrubs to late-season fires in higher-biomass forestlands. The proportion of total biomass loss attributed to wildfires in forestland areas increased from an average of 76% per year before 2015 to 94% in the years that followed. Furthermore, we found that recent droughts contributed to increased biomass loss in forestland areas, whereas biomass in non-forestland areas appeared unaffected by drought conditions. These findings underscore the escalating impact of climate change on fire regimes, highlighting the urgent need for adaptive land management strategies to mitigate carbon loss and preserve ecosystem resilience in the face of ongoing aridification.

ecology↗

bioRxiv2025

An activated wheat CCG10-NLR immune receptor forms an octameric resistosome

Nucleotide-binding and leucine-rich repeat (LRR) receptors (NLRs) are widespread intracellular immune sensors across kingdoms. In plants, the G10-type coiled-coil (CCG10)-NLRs form a distinct phylogenetic clade that remains poorly characterized. Here, we identified a gain-of-function (GOF) mutant of Wheat Autoimmunity 3 (WAI3), designated WAI3GOF, which encodes a constitutively activated CCG10-NLR protein due to an amino acid substitution. Cryo-EM structural analysis revealed that activated WAI3 assembles into a distinctive octameric resistosome. Arabidopsis RPS2, another CCG10-NLR, also forms an octamer, indicating a conserved structural property across monocot and dicot plants. The WAI3 resistosome mediates a prolonged and sustained increase in cytosolic calcium influx, facilitated by a unique channel architecture arising from its divergent CC domain configuration. Notably, this domain arrangement may be shared by many plant NLRs that lack the conserved EDVID motif in their CC domains. Our findings uncover a previously uncharacterized resistosome structure and provide insights into plant immune receptor plasticity.

plant biology↗

bioRxiv2025

Cost-effective genomic prediction for fertility traits: A comparison of machine learning and conventional models using low-coverage sequencing in Holstein heifers

Fertility is one of the major factors affecting the efficiency of dairy herd, and genomic selection (GS) on milk yield, while ignoring fertility, has resulted in a decline in heifer fertility. Consider the cost of breeding, it is important to enhance the accuracy of GS with cost-effective way for fertility traits. This study investigates the genomic prediction (GP) of fertility traits in Holstein heifers using both machine learning (ML) and conventional methods, based on data from SNP arrays and low-coverage sequencing data. In this study, we collected 45,320 Holstein heifers with phenotype and pedigree records, from which we generated genomic data for 3,683 Holstein heifers using lcGWS. We first estimated the heritability for age at first service (AFS), gestation length (GLh) and age at first calving (AFC). We then compared the prediction performance of ML methods, kernel ridge regression (KRR), support vector regression, and random forest regression, with GBLUP, ssGBLUP and BayesR3 regarding GP accuracy and unbiasedness. Inputs for ML includes genomic relationship matrices (GRM), principal components, and SNPs. The results revealed that the heritability for the three fertility traits ranged from 0.09 to 0.48. Prediction accuracy from imputed low-coverage sequencing data was comparable to that from standard SNP chips. When both pedigree and genotypic data were used for GS, ssGBLUP yielded the highest prediction accuracy for AFS and GLh. Crucially, using only genomic data, KRR_GRM improved GP accuracy by up to 28.57% compared to GBLUP and by up to 9.46% compared to BayesR3. Our results highlight the effectiveness of low-coverage sequencing data in breeding applications and the MLs potential to enhance GP accuracy for fertility traits, offering practical insights for dairy breeding programs. ImplicationsTo improve the accuracy of GS with cost-effective way for fertility traits, this study confirms that low-coverage sequencing offers both accuracy and cost-effectiveness for fertility in Holstein heifers. The research provides a decision-making framework for breeding workers: the ssGBLUP model is optimal when combining pedigree data, while machine learning methods are superior with only genomic data. This study offers a practical tool for achieving efficient and economical genetic improvement in dairy cattle.

genomics↗

bioRxiv2025

Genomic Regions and Variant Analysis Reveal Candidate Genes Associated with Age at First Service in Chinese Holstein Heifers

Understanding the genetic basis and identifying quantitative trait loci (QTL) for age at first service (AFS) is essential for improving reproductive efficiency and reducing economic costs in heifers rearing. We conducted a genome-wide association study (GWAS) for AFS using the genomic estimated breeding values (GEBVs) of 3,686 Chinese Holstein heifers, genotyped with 7,964,217 single nucleotide polymorphisms (SNPs) after quality control. Significant SNPs and candidate genes were identified and investigated through colocalization analysis of GWAS, expression QTL (eQTL), and splicing QTL (sQTL), and expression analysis in blood RNA sequencing (RNA-seq). The heritability estimate for AFS was moderate at 0.276 {+/-}0.025. Three QTL regions associated with AFS were identified: Region 1 on BTA6 (43688837-45007127 bp, 1.3 Mb with three 200kb windows), explaining 0.47% of genetic variance; Region 2 on BTA6 (62770788-62967316 bp) explaining 0.27% of the genetic variance; and Region 3 on BTA18 (6299721-6498934 bp) explaining 0.17% of the genetic variance. Combining GWAS and colocalization analysis, we identified ANAPC4, RBPJ, SEPSECS, SLC34A2, ZCCHC4, CCDC149, GNPDA2, GUF1, DHX15, SOD3, GUF1 and GNPDA2 as candidate genes. These genes are enriched in signaling pathways such as progesterone-mediated oocyte maturation, parathyroid hormone synthesis, secretion and action, and selenocompound metabolism. ANAPC4, DHX15, GUF1, SEPSECS, and SOD3 were also differently expressed genes (DEGs) in blood RNA-seq. Integrating the GWAS, colocalization, differential expression analysis, and existing literature, ANAPC4 and rs136363104 were highlighted as the putative causal gene and variant for puberty, respectively. In conclusion, our study identified three candidate regions and 12 candidate genes, confirming ANAPC4 as a putative causal gene influencing AFS. This research enhances the understanding of the genetic basis of AFS in Chinese Holstein heifers. The identified key genomic regions, candidate genes, and variants have the potential to improve reproductive efficiency and reduce economic costs in heifer rearing. Interpretative summaryThe economic burden of heifer-raising and reproductive inefficiency in dairy cattle is evident. The most important strategy for optimizing heifer-raising is selecting heifers with earlier puberty (sexual maturity) to shorten age at first service (AFS). In this study, we have identified key genomic regions and candidate genes on AFS in Chinese Holstein heifers by genome-wide association study, and validated them by colocalization and RNA-seq analysis. The findings have the potential to enhance the understanding of the genetic basis of reproductive traits, leading to more targeted breeding strategies for improved reproductive efficiency.

genetics↗

bioRxiv2025

Hyper-dominant species drive unexpected functional shifts in North American birds

Global environmental changes have led to widespread intraspecific shifts in functional traits across large numbers of widely distributed taxa. However, how within-species functional shifts predict community-level changes is unknown. We summarized seven key traits that are hypothesized to shift adaptively under environmental changes using local community-weighted means across North American bird communities. We find that communities shifted toward larger body mass and smaller appendage sizes over time, the opposite of widely observed within-species temporal changes in North American birds. These unexpected patterns arise from changes in the relative abundance of a very small number of hyper-dominant species, with 23 out of 470 (5%) species explaining the community-level trajectories in functional traits. These species are known to be heavily impacted--both positively and negatively--by human activities, and the idiosyncratic drivers of population sizes result in weak associations between community-level functional shifts and major bioclimatic variables but strong associations with human-induced land use changes. Our results illustrate the complexity in scaling from within-species responses to global change to community-level responses and highlight the importance of species-specific responses to the environment beyond climate when predicting functional and taxonomic diversity under global change.

ecology↗

bioRxiv2025

Human fibroblasts from aged individuals exhibit chromosomal instability through replication stress caused by oxidative stress

Aneuploid cells are known to increase with age. Previously, we demonstrated that aneuploid cells increase in fibroblasts from aged mice due to chromosomal instability (CIN), which is caused by oxidative stress. It is unclear whether this phenomenon also occurs in human cells, which are more resistant to oxidative stress than mouse cells. Here, we found that fibroblasts from aged individuals exhibited an increase in aneuploid cells. The frequency of chromosome missegregation and micronuclei increased in these cells, indicating CIN. A DNA fiber assay revealed the presence of replication stress, accompanied by an increase in 53BP1 nuclear bodies and ultrafine bridges. Increased levels of reactive oxygen species derived from mitochondria, along with reduced mitochondrial membrane potential, imply that these cells experienced oxidative stress due to mitochondrial functional decline. Antioxidant treatment reduced the frequency of chromosome missegregation and micronuclei, suggesting that oxidative stress causes CIN. Oxidative stress also causes replication stress, which precedes CIN. Spindle microtubules were stabilized in fibroblasts from aged individuals, which was alleviated by antioxidant treatment. Taken together, these findings suggest that aging-related CIN in human fibroblasts is caused by oxidative stress associated with mitochondrial dysfunction, which induces replication stress that in turn causes CIN through microtubule stabilization. Although human fibroblasts are more resistant to the ambient oxygen environment than mouse fibroblasts, our findings showed that they undergo oxidative stress that causes CIN with age in a manner similar to mouse fibroblasts, revealing a conserved phenomenon in mammalian cells.

cell biology↗

bioRxiv2025

Human placental stem cells induce a novel multiple myeloid cell-driven immunosuppressive program that ameliorates proinflammatory CNS pathology

Despite a growing interest in Amniotic Epithelial Cell (AEC)-based therapies, the immune responses triggered by AEC transplantation in vivo remain poorly characterized. In particular, how direct exposure to AECs within the central nervous system (CNS) shapes the local immune environment is currently unknown. Herein we describe a novel CNS- specific immunoregulatory pathway induced by intracisternal delivery of human AECs. Local immune responses induced by AECs in the brain led to recruitment of immunosuppressive Arginase 1+ (ARG1+) macrophages and a novel population of myeloid-derived suppressor cells with eosinophilic characteristics, which we term Eo- MDSCs. We further demonstrate that Eo-MDSCs produce Maresin 2 (MaR2), a specialized pro-resolving mediator (SPM) involved in the resolution of inflammation. In a mouse model of Multiple Sclerosis (MS), treatment of established disease with AECs induced immunological responses that resulted in reduced numbers of pathogenic macrophages and T helper (TH)17 cells, increased anti-inflammatory T cell subsets, and enhanced myelin phagocytosis, all of which led to functional recovery. These findings suggest that AEC therapy has the potential to target CNS-intrinsic inflammatory processes in MS, providing a strong rationale for translation into the clinic.

neuroscience↗

bioRxiv2025

cfDNAanalyzer: a comprehensive toolkit for analyzing cell-free DNA genomic sequencing data in liquid biopsy

Liquid biopsy, through the analysis of plasma cell-free DNA (cfDNA), is transforming diagnostic medicine by enabling non-invasive insights into the genomic and epigenomic landscape of diseases--most notably cancer. As cfDNA reflects dynamic contributions from multiple tissues, it holds immense potential for early detection, disease monitoring, and personalized treatment. However, the rapid expansion of cfDNA applications has outpaced the availability of unified, versatile computational tools for the systematic analysis of cfDNA data. To address this unmet need, we present cfDNAanalyzer--a comprehensive, user-friendly toolkit that streamlines the feature extraction, selection, and construction of machine learning-based models for disease detection using cfDNA. Designed for flexibility and scalability, cfDNAanalyzer supports multimodal feature extraction, integration, and interpretable outputs, enabling both exploratory research and translational applications. By standardizing and accelerating cfDNA data analysis, cfDNAanalyzer provides a critical resource to advance precision diagnostics and deepen biological insight into disease processes.

bioinformatics↗

bioRxiv2025

Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose

Crosstalk between the post-translational modification processes ubiquitination and ADP-ribosylation occurs in DNA-damage and immune-responses, in addition the physical linkage of ADP-ribose and ubiquitin is found during bacterial infection. Here, we study the ubiquitination of ADP-ribose mediated by human Deltex E3 ligases and the subsequent fate of the formed hybrid post-translational modification. We prepare a non-hydrolysable ADPr-Ub probe that we employ in a chemoproteomics approach and identify RNF114 as an interacting protein. Using biophysical and biochemical experiments, we validate that RNF114 preferentially interacts with ubiquitinated ADP-ribose over non-modified ubiquitin. Subsequently, RNF114 can elongate the ubiquitinated ADP-ribose with a K11-linked ubiquitin chain. Using domain deletion analysis, we pinpoint the tandem zinc fingers and ubiquitin interacting motif (ZnF2+ZnF3+UIM) domains of RNF114 to be crucial for recognising ubiquitinated ADP-ribose. Moreover, these domains are essential for the recruitment of RNF114 to the sites of laser-induced DNA damage.

molecular biology↗

bioRxiv2025

TMEDs Mediate Versatile Cargo Transport in Vesicle-dependent Unconventional Secretion

Unconventional protein secretion (UcPS) exports diverse signal peptide-lacking cargoes, yet its cargo selectivity remains poorly understood. Here, we identify TMED proteins as key regulators of vesicle-dependent UcPS, mediating selective cargo release via translocation into secretory carriers. TMED proteins act as translocators, facilitating cargo passage across lipid bilayers with assistance from HSP90 chaperones and partial cargo unfolding. Selectivity arises during translocation, where TMED cytoplasmic tails bind specific cargoes. The ER-Golgi intermediate compartment (ERGIC) is essential for TMED-mediated translocation and release. TMED homo-oligomerization enhances translocation, while hetero-tetramerization inhibits it. ERGIC localization promotes homo-oligomerization, which is further stabilized by cargo binding, forming a feed-forward mechanism to enhance translocation. These findings establish TMED proteins as central regulators of cargo diversity in UcPS, with their oligomerization and subcellular localization modulating translocation efficiency.

cell biology↗

bioRxiv2025

The China Brain Multi-omics Atlas Project (CBMAP)

The China Brain Multi-omics Atlas Project (CBMAP) aims to generate a comprehensive molecular reference map of over 1,000 human brains (Phase I), spanning a broad age range and multiple regions in China, to address the underrepresentation of East Asian populations in brain research. By integrating genome, epigenome, transcriptome, proteome (including multiple post-translational modifications), and metabolome data, CBMAP is set to provide a rich and invaluable resource for investigating the molecular underpinnings of aging-related brain phenotypes and neuropsychiatric disorders. Leveraging high-throughput omics data and advanced technologies, such as spatial transcriptomics, proteomics, and single-nucleus 3D chromatin structure analysis, this atlas will serve as a crucial resource for the brain science community, illuminating disease mechanisms and enhancing the utility of data from genome-wide association studies (GWAS). CBMAP is also poised to accelerate drug discovery and precision medicine for brain disorders.

neuroscience↗