Biology subjects

Jin, C.

Publications and source records attributed to Jin, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

AncientMetagenomeDir dating metadataset highlights need for standardised radiocarbon reporting in ancient DNA

Ancient DNA is a valuable data source for the understanding of our past. However, to effectively interpret this data, it is essential to know the age of the samples from which the DNA is obtained. Although the field of palaeogenomics has been recognised for its robust open data sharing practices, dating information associated with analysed samples is not reported consistently across palaeogenomic studies, nor is it included as metadata in most genetic data repositories. Here, we describe the addition of standardised precise dating information for ancient microbial genomes into the AncientMetagenomeDir metadata repository of published ancient metagenomic samples. This extension currently includes dating information for over 700 ancient microbial genomic datasets, of which 333 are dated using historical, contextual, or stratigraphic methods, and 405 are radiocarbon dated. We quantitatively assess the quality of radiocarbon date reporting and find that, despite established reporting conventions, radiocarbon dating information is often reported inconsistently across ancient metagenomic studies. This new resource provides ancient microbial researchers with standardised dating information that facilitates more accurate and consistent analysis of metagenomic sequencing data. The dataset also highlights the need for greater standardisation of radiocarbon date reporting in original publications in order to allow effective reuse of this and future ancient microbial data.

bioinformatics↗

bioRxiv2026

Lifestyle impacts the oral microbiome of Classical and Post-classical societies in Italy

ObjectivesThe fall of the Roman Empire (476 CE) profoundly affected the lives of its peoples due to the political, administrative, and territorial changes that occurred. The majority of written records of the time focus on the social elite, leaving larger parts of the population understudied. Here, we employ a bioarchaeological approach to understand how differences in lifestyle may be reflected in the oral microbiome of people from different social classes living before and after the fall. Material and MethodsWe analysed shotgun sequencing data from dental calculus, the preserved oral microbiome, of 67 individuals belonging to different social classes from two Classical cemeteries dated to I-III century CE (Lucus Feroniae and Isola Sacra) and one post-Classical cemetery dated to IV-VIII century CE (Selvicciola), all located in proximity to the city of Rome, Italy. ResultsWe detect significant differences in the oral microbiome taxonomic and functional composition across time periods and social classes, with the rural town of Lucus Feroniae standing out compared to its two counterparts. Reliable identification of dietary items was not possible. DiscussionThe distinct oral microbiome of Lucus Feroniae could reflect differences in general health and subsistence practices. The rural position of this community may have mitigated the cyclical food crises that, instead, affected the contemporary Isola Sacra and the later community of Selvicciola, thereby buffering against the nutritional stress observed in these two locations.

genomics↗

bioRxiv2026

Astrocyte stimulation reopens the window of the critical period for the experience-dependent plasticity of retinogeniculate synapses

A specific time window during which neural circuits undergo dramatic changes in response to individual experiences is known as the critical period (CP). Developing methods to reopen the CP after its closure could lead to the establishment of effective treatment approaches. The retinogeniculate (RG) synapses in the dorsal lateral geniculate nucleus (dLGN) undergo experience-dependent remodeling only during the limited period of development. We investigated the effects of astrocyte manipulation on the restoration of RG synapse plasticity after the CP termination. Astrocytic stimulation with the designer receptors exclusively activated by designer drugs (DREADD) after the CP closure caused RG synapse remodeling in the dark-reared mice but not in those reared in normal conditions. Single-nucleus RNA sequencing (snRNA-seq) of dLGN astrocytes implicated the underlying mechanisms of astrocyte-induced RG synaptic plasticity. Therefore, astrocytes can regulate the susceptibility of RG synapses to experience-dependent plasticity after CP termination.

neuroscience↗

bioRxiv2025

Temporal Multi-Omic Analysis Uncovers Sex-Biased Molecular Programs Underlying Skeletal Muscle Adaptation to Endurance Training

BackgroundExercise training is known to benefit health and reduce disease risk. While skeletal muscle adaptations are fundamental to many of the health benefits of exercise training, the common and sex-specific molecular regulators that mediate these adaptations remain to be fully elucidated. MethodsTo this end, we leveraged skeletal muscle multi-omics data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), where 6 month-old male and female rats endurance trained for 1, 2, 4, or 8 weeks. Our objective was to identify shared and sex-specific multi-omic molecular responses to endurance training in skeletal muscle, and relate them to phenotypic adaptations. ResultsWe identified largely sexually-conserved transcriptomic and proteomic pathway enrichments in the gastrocnemius, which correlated with skeletal muscle responses from a published exercise study in humans. We uncovered sex-consistent post-translational modifications, including decreased oxidation of MYH2 and deacetylation of the {beta}-oxidation enzyme HADHA. Pathway enrichment analyses revealed sex-specific remodeling across the acetylome, redox proteome, and phosphoproteome; females decreased mitochondrial protein cysteine oxidation and increased mitochondrial cristae proteins, indicative of enhanced redox buffering and mitochondrial efficiency. Despite decreases in cysteine oxidation of key mitochondrial proteins, females displayed increases in the cysteine oxidation of proteins involved in glucose catabolism relative to males after 8 weeks of training, suggestive of sex-biased subcellular reactive oxygen species generation. Males demonstrated earlier induction of mitochondrial transcripts and predicted activation of mTOR. Although the increase in mitochondrial protein abundance was more modest in males, there was greater oxidation of mitochondrial proteins in response to training compared to females. ConclusionsThis work shows a large portion of the adaptive response to endurance training in skeletal muscle is shared between females and males, while there are distinct and nuanced sex-specific adaptations that are evident, particularly at the level of post-translational regulation.

physiology↗

bioRxiv2025

Extended nuclear glycosylation is a common post-translational modification

In eukaryotes, glycans modify proteins in the secretory pathway and the extracellular space. Aside from nucleocytoplasmic O-GlcNAc, glycosylation is not considered a relevant post-translational modification in other cellular compartments. Here, we challenge this long-standing paradigm by showing that extended O-glycans are commonly found on intranuclear proteins. Through comprehensive genetic and biochemical analyses, we conclusively demonstrate that these O-glycans stem from the secretory pathway, yet are found on nuclear proteins across mammalian cell lines and primary cells. Using knock-out cell lines, we show mechanistically that nuclear glycans are shuttled to the nucleus via active vesicular transport. We identify several of these intranuclear glycoproteins as RNA-binding proteins, including KHSRP/FUBP2, RBM12, and RPP30. Lastly, we show that site-specific glycosylation of RPP30 is crucial for effective tRNA processing. Overall, our findings suggest a much broader role for glycosylation in regulating cellular functions and open up investigation into the role of glycans in more biological processes.

molecular biology↗

bioRxiv2025

The role of Akkermansia muciniphila sulfatases in colonic mucinutilisation

Akkermansia muciniphila, an obligate mucin degrader, is a major member of the human colonic microbiota and has been associated positive health outcomes. Mucins are complex glycoproteins that contain heavily sulfated O-glycans and form the protective colonic mucus layer. Bacterial carbohydrate sulfatases are required to metabolise these heavily sulfated mucin glycans and excessive bacterial foraging has been associated with several diseases. Sulfatases have been linked with inflammatory bowel disease, making these microbiota enzymes potential drug targets. A. muciniphila expresses carbohydrate sulfatases that can act on colonic mucins yet their roles in its metabolism remain opaque. Our data reveal that A. muciniphila requires glycopeptides/protein forms of colonic mucin for metabolism and its sulfatases have unique adaptations compared to Bacteroides species. Localisation studies reveal that desulfation of N-acetyl-D-glucosamine, but not D-galactose, is exclusively periplasmic. A cell surface sulfatase has a novel carbohydrate binding module that binds to colonic mucin. This paints a contrasting picture of sulfated mucin metabolism by Akkermansia muciniphila versus Bacteroides species. These data will be important for understanding the contexts for Akkermansia muciniphilas positive health correlations.

biochemistry↗

bioRxiv2025

Ergothioneine and a new food supplement product protectagainst cyclophosphamide-induced premature ovarianfailure in rats

Premature ovarian failure (POF) is characterized by disrupted estrous cycles and impaired folliculogenesis due to oxidative stress and inflammation. In this study, a cyclophosphamide (CTX)-induced POF rat model was used to evaluate the protective effects of ergothioneine (EGT) and a nutraceutical formula (FineNutri Cellular Vitality Capsules) containing EGT. CTX treatment markedly prolonged the estrous cycle, reduced estrus duration, decreased ovarian weight, impaired follicular development, and increased granulosa cell apoptosis. Serum estradiol (E2) and anti-Mullerian hormone (AMH) levels decreased, whereas luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increased, reflecting disruption of the hypothalamic-pituitary-ovarian axis by CTX. CTX treatment induced oxidative stress, with reduced catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content, and increased malondialdehyde (MDA) in ovarian tissue. The EGT and the nutraceutical formula restored estrous cycles, increased ovarian weight, improved primordial follicle counts, and reduced atretic follicles and granulosa cell apoptosis. Hormonal balance was partially restored, with increased E2 and AMH and reduced LH and FSH levels. Oxidative stress was alleviated with higher CAT, SOD, and GSH levels and reduced MDA concentrations. In addition, EGT and the formula reduced inflammation in skin tissue. These findings suggest that EGT and the nutraceutical formula could protect against CTX-induced POF and help preserve ovarian function, probably by mitigating oxidative stress.

pharmacology and toxicology↗

bioRxiv2025

Dual human milk oligosaccharide-fibre utilisation drives gut microbiome selection during weaning

Gut microbiome (GM) maturation in early life follows organised taxonomic successions. How weaning impacts these trajectories remains underexplored. Here, we sampled faeces from seven mother-infant dyads at pre-, early and late weaning. Enrichment cultures (n=306) and metagenomic (n=108) analyses revealed an unexpected prevalence of fibre degradation genes and the growth of the pre-weaning infant GM on common dietary fibres. Utilisation of both human milk oligosaccharides (HMOs) and dietary fibres was revealed as a metabolic hallmark of the weaning GM. We showed that HMO-utilisation is retained beyond weaning, by analyses of maternal GM and HMO utilisation in 137 maternal isolates. Our findings highlight dual HMO-dietary fibre utilisation as a hitherto unrecognised driver that potentially orchestrates the selection of distinct adult GM species during weaning. This work outlines a plausible mechanism underlying the organised GM maturation in early life and highlights a previously overlooked role of HMOs during the weaning transition.

microbiology↗

bioRxiv2025

The Impact of New Urbanization on Quantity Increase and Quality Improvement of Green Innovation: Based on Multivariate Moderating Effect Models

New urbanization is a major national strategy that China has proposed and implemented. Whether new urbanization (NEU) can promote quantity increase and quality improvement of green innovation (GI) is a common concern of the government and scholars. This paper empirically analyzes quantity increase and quality improvement effects of new urbanization on urban GI by adopting the panel data of each city from 2011 to 2022. The study finds that new urbanization not only has a positive contribution to the quantity increase of GI in cities but also plays a positive role in the quality improvement of GI. Digital inclusive finance will further amplify the dividends of new urbanization and exert the GI effect. The interaction of digital inclusive finance and government support, informatization, regional economic development, and energy consumption also amplify the dividends of NEU and exert strong "quantity increase" and "quality improvement" effects on GI. The stronger the governments green support, the more conducive it is to new urbanization to further exert quantity increase and quality improvement effects on GI. The conclusions of this paper have important policy implications for further promoting the construction of new urbanization and GI.

ecology↗

bioRxiv2025

Genomic Touchstone: Benchmarking Genomic Language Models in the Context of the Central Dogma

The emergence of genomic language models (gLMs) has revolutionized the analysis of genomic sequences, enabling robust capture of biologically meaningful patterns from DNA sequences for an improved understanding of human genome-wide regulatory programs, variant pathogenicity and therapeutic discovery. Given that DNA serves as the foundational blueprint within the central dogma, the ultimate evaluation of a gLM is its ability to generalize across this entire biological cascade. However, existing evaluations lack this holistic and consistent framework, leaving researchers uncertain about which model best translates sequence understanding into downstream biological prediction. Here we present Genomic Touchstone, a comprehensive benchmark designed to evaluate gLMs across 36 diverse tasks and 88 datasets structured along the central dogmas modalities of DNA, RNA, and protein, encompassing 5.34 billion base pairs of genomic sequences. We evaluate 34 representative models encompassing transformers and convolutional neural networks, as well as emerging efficient architectures such as Hyena and Mamba. Our analysis yield four key insights. First, gLMs achieve comparable or superior performance on RNA and protein tasks compared to models pretrained on these molecules. Second, transformer-based models continue to lead in overall performance, yet efficient sequence models show promising task-specific capabilities and deserve further exploration. Third, the scaling behavior of gLMs remains incompletely understood. While longer input sequences and more diverse pretraining data consistently improve performance, increases in model size do not always translate into better results. Fourth, pretraining strategies, including the choice of training objectives and the composition of pretraining corpora, exert substantial influence on downstream generalization across different genomic contexts. Genomic Touchstone establishes a unified evaluation framework tailored to human genomics. By spanning multiple molecular modalities and biological tasks, it offers a valuable foundation for guiding future gLM design and understanding model generalizability in complex biological contexts.

bioinformatics↗

bioRxiv2025

Central nervous system atlas of larval zebrafish constructed using the morphology of single excitatory and inhibitory neurons

Single-neuron morphology mapping is fundamental for deciphering brain architecture and function, yet in vertebrates it remains limited in spatial coverage and cell-type information. Here we present a nervous system-wide single-neuron morphology atlas of larval zebrafish with annotated excitatory/inhibitory identity and dendrite-axon polarity. The atlas comprises >20,000 reconstructed neurons from >13,400 animals, spanning the central and peripheral nervous system and representing [~]24.5% of the total excitatory and inhibitory neurons in the brain, all integrated into a common physical space with neuroanatomical parcellations. We define >500 excitatory and inhibitory neuronal morphotypes and construct putative inter-cell-type and interregional connectomes. Projection and morphotype analyses reveal distinct laterality and directionality biases and modular innervation patterns in excitatory and inhibitory neurons, while network analyses uncover fundamental connectivity motifs, hubs, and sensorimotor pathways. Accessible through custom-built interactive platform ZExplorer, this atlas provides a foundational resource for multimodal data integration, circuit analysis, computational modeling, and hypothesis-driven research.

neuroscience↗

bioRxiv2025

Specialized parallel pathways for adaptive control of visual object pursuit

To pursue a moving visual object, the brain must generate motor commands that continuously steer the object to the center of the visual field via feedback. The gain of this control loop is flexible, yet the biological mechanisms underlying such adaptive control are not well-understood. Here we show that adaptive control in the Drosophila pursuit system involves two parallel pathways. One detects objects in the periphery and steers them toward the center of the visual field. The other detects objects near the center of the visual field and steers them to the visual midline. This latter pathway is flexible: gain increases when the object is moving away from the midline and when the pursuer is running fast. This latter pathway is also preferentially recruited when the fly is aroused, and suppressing it decreases pursuit performance. Our findings demonstrate how adaptive control can emerge from parallel pathways with specialized properties.

neuroscience↗

bioRxiv2025

Single-Cell eQTL Mapping Reveals Cell Type-Specific Genetic Regulation in Lung Cancer

Genome-wide association studies (GWAS) have identified over 50 lung cancer risk loci; however, the precise cellular context of these genetic mechanisms remains unclear due to limitations in bulk tissue eQTL analyses. Here, we present the largest single-cell eQTL atlas of human lung tissue to date, profiling 222 donors using multiplexed scRNA-seq. We identified 16,785 eQTLs across 17 cell types, with over 90% of sc-eQTLs and 59% eGene being cell-type-specific, and fewer than 23% were detectable in paired bulk datasets. Integration with GWAS for non-small cell lung cancer highlighted epithelial and immune cells as key contributors to genetic susceptibility, identifying 28 candidate genes within known risk loci and 24 in novel regions. Notably, 47% of established NSCLC susceptibility loci exhibited cell-type-specific pleiotropic genetic regulation. This study provides a valuable resource of lung sc-eQTLs and illuminates how genetic variation modulates gene expression in a cell-type-specific fashion, contributing to lung cancer susceptibility.

genetics↗

bioRxiv2025

Alectinib enhances response to RBM39 degradation via SRPK1 inhibition

Precise control of pre-mRNA splicing is critical for transcriptome integrity, and its disruption is increasingly recognised as a vulnerability in cancer. Here, we identify a functional interplay between two key splicing regulators, RBM39 and serine/arginine protein kinase 1 (SRPK1), and show that dual targeting of these factors severely compromises splicing fidelity in high-risk neuroblastoma. We use the molecular glue indisulam to degrade RBM39 and repurpose the clinical ALK inhibitor alectinib which potently inhibits SRPK1. Co-treatment with indisulam and alectinib inhibited cell proliferation, induced apoptosis, and caused G2/M arrest in multiple cancer cell lines, including MYCN-amplified neuroblastoma. RNA sequencing revealed enhanced splicing defects preferentially in DNA repair and genome maintenance related genes following combination treatment, leading to R-loop accumulation and increased DNA damage. In the Th-MYCN/ALKF1174L neuroblastoma mouse model, combination therapy induced complete tumour regression and significantly improved survival rates compared with monotherapies. These findings demonstrate that combining indisulam and alectinib is a promising approach to treat aggressive malignancies such as high-risk neuroblastoma, exploiting the previously untapped polypharmacology of alectinib as a clinical RNA splicing inhibitor and supporting the therapeutic value of co-targeting interdependent splicing factors for synergistic benefit.

cancer biology↗

bioRxiv2025

Seal milk oligosaccharides rival human milk complexity and exhibit functional dynamics during lactation

Breast milk oligosaccharides are crucial for neonatal development and health. Yet most milk research focuses on humans, or domesticated mammals that are historically poor in milk oligosaccharide complexity. Here, we perform an exhaustive mass spectrometry-driven structural characterization of milk oligosaccharides in a wild mammal, Atlantic grey seals (Halichoerus grypus), throughout their lactation period. Characterizing and quantifying 332 milk oligosaccharides, including 166 novel structures, we reveal seals to rival human milk in complexity, with seal free oligosaccharides reaching unprecedented 28 monosaccharides in size. Glycomics and metabolomics time course analysis establishes a concerted regulatory process reshaping the seal milk glycome throughout lactation,similar as in human milk. Functional analysis of herein newly characterized structures reveals anti-biofilm effects and immunomodulatory functions of seal milk oligosaccharides. We envision these findings to overturn long-held assumptions about milk complexity of non-human mammals and enable insights into the functional relevance of complex carbohydrates in breast milk.

biochemistry↗

bioRxiv2025

Disinfecting eukaryotic reference genomes to improve taxonomic inference from ancient environmental metagenomic data

Ancient environmental DNA is increasingly essential for reconstructing past ecosystems, particularly when palaeontological and archaeological tissue remains are absent. Detecting ancient plant and animal DNA in environmental samples often relies on using extensive eukaryotic reference genome databases for profiling shotgun metagenomics data. However, microbial contamination in these references can introduce substantial biases in taxonomic assignments, especially given the typical low abundance of plant and animal DNA in such samples. In this study, we present a method for identifying bacterial and archaeal-like sequences in eukaryotic genomes and apply it to nearly 3,000 reference genomes from NCBI RefSeq and GenBank (vertebrates, invertebrates, plants) as well as the 1,323 PhyloNorway plant genome assemblies from herbarium material from northern high-latitude regions. Our analysis reveals microbial-like sequences in many eukaryotic reference genomes, which are most pronounced in the PhyloNorway dataset. We provide a detailed map of the microbial-like regions, including genomic coordinates and taxonomic annotations. This resource enables the masking of microbial-like regions during profiling analyses, thereby improving the reliability of ancient environmental metagenomic datasets for downstream analyses.

genomics↗

bioRxiv2025

Resilience and vulnerabilities of tumor cells under purine shortage stress

Purine metabolism is a promising therapeutic target in cancer; however how cancer cells respond to purine shortage,particularly their adaptation and vulnerabilities, remains unclear. Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated these responses in prostate, lung and glioma cancer models. We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multi-protein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. While this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the microtubule-stabilizing chemotherapeutic drug Docetaxel. Furthermore, we show that although cancer cells primarily rely on de novo purine biosynthesis, they also exploit Methylthioadenosine Phosphorylase (MTAP)-mediated purine salvage as a crucial alternative source of purine supply, especially under purine shortage stress. In support of this finding, combining DRP-104 with an MTAP inhibitor significantly enhances tumor suppression in prostate cancer (PCa) models in vivo. Finally, despite the resilience of the purine supply machinery, purine shortage-stressed tumor cells exhibit increased DNA damage and activation of the cGAS-STING pathway, which may contribute to impaired immunoevasion and provide a molecular basis of the previously observed DRP-104-induced anti-tumor immunity. Together, these findings reveal purinosome assembly and purine salvage as key mechanisms of cancer cell adaptation and resilience to purine shortage while identifying microtubules, MTAP, and immunoevasion deficits as therapeutic vulnerabilities.

cancer biology↗

bioRxiv2025

Formaldehyde induces and promotes Alzheimer's disease pathologies in a 3D human neural cell culture system

Alzheimers disease (AD) arises from complex multilevel interactions between genetic, epigenetic, and environmental factors. Recent studies suggest that exposure to the environmental and occupational toxicant formaldehyde (FA) may play a significant role in AD development. However, the effects of FA exposure on A{beta} and tau pathologies in human neural cell 3D culture systems remain unexplored. To investigate FAs role in AD initiation, we differentiated 3D-cultured immortalized human neural progenitor ReN cells (ReNcell VM) into neurons and glial cells, followed by FA treatment. FA exposure for 12 weeks resulted in a dose-dependent increase in A{beta}40, A{beta}42, and phosphorylated tau levels. To further examine FAs role in AD progression, we established a 3D human neural cell culture AD model by transfecting ReN cells with AD-related mutant genes, including mutant APP and PSEN1, which recapitulate key AD pathological events. Our findings demonstrate that FA exposure significantly elevated A{beta}40, A{beta}42, and phosphorylated tau levels in this 3D-cultured AD model. These results suggest that FA exposure contributes to the initiation and progression of AD pathology in 3D-cultured human neural cells.

neuroscience↗