Biology subjects

Liu, D.

Publications and source records attributed to Liu, D..

At least 73 records · Page 4Linked to original sources

bioRxiv2026

Near completely reversing the γ- to β-globin switch by enhancer release, retargeting and reinforcing

The {gamma}- to {beta}-globin switch is intricately regulated during human ontogeny, and this process is manipulated for therapeutic approaches to treat {beta}-hemoglobinopathies by activating {gamma}-globin expression. Several genetic strategies to reactivate HbF have partially reversed the {gamma}- to {beta}-globin switch and ameliorated the clinical symptoms of {beta}-hemoglobinopathies. However, whether the {gamma}- to {beta}-globin switch can be completely reversed remains unknown. Completely reversing the {gamma}- to {beta}-globin switch requires a thorough redirection of the locus control region (LCR) from interacting with the {beta}-globin gene (HBB) to interacting with the {gamma}-globin gene (HBG). Here, we found that disrupting the KLF1-mediated HBB-LCR interaction by mutating the CACCC motif in HBB leads to the release of the LCR and its retargeting to other {beta}-like globin genes. Moreover, simultaneously disrupting the KLF1-mediated HBB-LCR interaction and the epigenetic repression of HBG by combined editing of the CACCC motif in HBB and the TGACCA motif in HBG reinforces the HBG-LCR interaction, resulting in almost exclusive {gamma}-globin expression while nearly absent {beta}-globin expression, achieving near complete reversal of the {gamma}- to {beta}-globin switch. This finding demonstrates the comprehensive regulation of the {gamma}- to {beta}-globin switch by gene competition and gene silencing mechanisms. This finding also suggests that silenced genes can be fully activated through the redirection of enhancer-promoter contacts and that the specificity of enhancer-promoter contact within chromosomal domains is achieved through the transcription factor clusters binding to enhancers and promoters. Combined editing of the CACCC&TGACCA motifs also offer a more optimal therapeutic strategy for {beta}-hemoglobinopathies.

molecular biology↗

bioRxiv2026

Prime-InDel version 1: A web tool providing InDel markers for targeted regions narrowing

While high-density SNP genotyping enables genome-wide assays in rice (Oryza sativa L.) and other crops, PCR-based markers--particularly those derived from insertion-deletion (InDel) variations--remain crucial for fine-mapping. Currently, readily available primer information for high-density InDel rice markers is still limited. We present the first version of PrimeInDel (https://rfgb.rmbreeding.cn/search/variation/primeIndel), an online tool integrating three sets of InDel markers: an 8K-set and a 316K-set from the 3K Rice Genomes (3K-RG) project, and a 22K-set compiled from published literatures. In user cases, primers from PrimeInDel proved highly effective, narrowing a cold-tolerance QTL (qSR2) from 2.7 Mb to 200 kb and a heading-date QTL (qDeh1.1) from 239.5 kb to 83.6 kb. Our work provides the community with a robust, PCR-based InDel primer, accessible via an online data set, which will facilitate germplasm genotyping and gene identification in rice breeding.

plant biology↗

bioRxiv2026

Pan-genome and multi-omics analyses reveal the genomic basis of symbiotic evolution in the mycoheterotrophic medicinal orchid Gastrodia elata

Mycoheterotrophy represents an extreme evolutionary strategy in which plants abandon photosynthesis and become obligately dependent on fungal partners for carbon and nutrients. Gastrodia elata, a medicinal orchid forming long-term symbioses with Armillaria and Mycena, provides a compelling system to investigate the genomic basis of obligate plant-fungus mutualism. Here, we generate a chromosome-level genome assembly (1.09 Gb) of a dark-red G. elata accession and construct a pan-genome from 12 Gastrodia accessions to dissect the evolutionary consequences of mycoheterotrophy. Phylogenomic analyses reveal pervasive hybridization across cultivated germplasm and demonstrate that tuber morphology more accurately reflects intraspecific relationships than stem color, challenging the traditional color-based taxonomy. Comparative genomic analyses reveal a pronounced degeneration of photosynthetic capacity. We detect no intact nuclear-encoded rbcS loci, which would preclude assembly of the Rubisco holoenzyme and thus canonical Calvin-Benson carbon fixation. Notably, a subset of photosynthesis-related genes is retained and transcriptionally active, suggesting their co-option into non-photosynthetic regulatory roles. Despite millions of years of intimate association with fungal partners, we detect no evidence of fungal-derived horizontal gene transfer based on a multi-step phylogenomic validation pipeline, indicating that G. elata-fungus mutualism is sustained through metabolic exchange rather than genetic integration. We further identify the Gastrodia antifungal protein (GAFP) gene family as a key molecular innovation underlying symbiotic homeostasis. The recently derived Class 1 GAFP lineage exhibits distinct domain architecture, tandem expansion, and elevated expression, consistent with enhanced regulation of fungal overgrowth. Finally, we delineate a specialized nutrient-acquisition framework adapted to obligate heterotrophy, in which fungal trehalose hydrolysis supplies hexose carbon via an expanded sugar transporter protein (STP) repertoire, while organic nitrogen is assimilated through amino acid and oligopeptide transporters coupled with urease-mediated conversion, compensating for the loss of nitrate uptake and reduction pathways. Together, these results establish a pan-genomic blueprint for symbiotic adaptation and reductive genome evolution in G. elata.

genomics↗

bioRxiv2026

Genomic diversity, antibiotic resistance, and maturation-dependent adhesion of F18 enterotoxigenic Escherichia coli strains in porcine intestinal cells

Enterotoxigenic Escherichia coli (ETEC) strains expressing F4 and F18 fimbriae are major causes of neonatal and post-weaning diarrhea in swine. Although epithelial maturation influences susceptibility in vivo, its impact on ETEC-host interactions remains poorly defined. This study characterizes emerging F18 ETEC isolates using a differentiated porcine intestinal cell model. Three F18 strains (3EC1, 27EC1, 3247EC), a porcine F4 strain, and human ETEC H10407 were analyzed by comparative genomics for virulence factors, toxin genes, and antimicrobial resistance determinants. Adhesion assays were performed using IPEC-1, IPEC-J2, and Caco-2 cells conditioned to Early (6 days post-confluence, DPC), Mid (9 DPC), and Late (16 DPC) maturation states. Transcription of F18-binding receptors (FUT1, FUT2) was quantified by RT-qPCR. IPEC-1 cells exhibited significantly higher FUT1 and FUT2 expression than IPEC-J2, corresponding to approximately two-fold stronger adhesion by most F18 isolates. Strain 3EC1 showed a distinct adhesion peak at 9 DPC, approaching F4 levels, while F4 and H10407 consistently displayed the highest adhesion across all models. Genomic analyses revealed substantial heterogeneity among F18 strains in fimbrial loci, flagellin, lipopolysaccharide biosynthesis, and antimicrobial resistance. Strain 3EC1 uniquely carried stx2e, and non-classical EAST1 variants were detected in 3EC1 and 3247EC. All F18 isolates encoded hlyE and were {beta}-hemolytic; 3247EC harbored 28 antimicrobial resistance genes. The IPEC-1/IPEC-J2 maturation stages recapitulate age-dependent susceptibility to ETEC, likely driven by FUT1/2 expression levels. The combination of strong adhesion, stx2e, and extensive antimicrobial resistance in F18 strains underscores their evolving virulence and supports this model as a refined platform for studying porcine ETEC pathogenesis. ImportanceETEC remains a leading cause of neonatal and post-weaning diarrhea in swine, yet the biological basis for age-dependent susceptibility is not fully understood. This study demonstrates that maturation of porcine intestinal epithelial cells strongly influences F18 ETEC adhesion, driven in part by developmental regulation of the F18-binding receptors FUT1 and FUT2. By integrating comparative genomics with a physiologically relevant in vitro maturation model, we reveal substantial diversity in virulence and resistance among F18 strains, including strong adhesion capacity, stx2e, and extensive antimicrobial resistance in strain 3EC1. These findings highlight the evolution of ETEC toward increased persistence and pathogenic potential in swine populations. The interaction between the maturation-dependent IPEC-1 and IPEC-J2 cell lines and ETEC offers a valuable tool for evaluating intervention strategies to reduce weaning piglet susceptibility to ETEC infection.

microbiology↗

bioRxiv2026

The overall and sequence-specific degradation of soil extracellular 16S rRNA genes across China: rates and influential factors

While extracellular DNA persistence substantially influences soil microbiome investigations, its degradation kinetics remain poorly quantified. Here, we developed a primer-labeled DNA approach coupled with microcosm incubation to determine the overall and sequence-specific degradation rates of extracellular DNA amplicon fragments across China. We observed substantial variations in the overall degradation rates of extracellular 16S rRNA gene amplicon fragments among the study sites, with degradation rate constants ranging from 0.05 to 0.16 day-1. The overall degradation rate constants showed significant correlations with soil moisture content, prokaryotic abundance, prokaryotic community profiles, and mean annual precipitation (MAP). The significant influences of moisture content on the overall degradation rates were further verified by a moisture gradient microcosm experiment. The sequence-specific degradation rate constant profiles were additionally correlated with pH, nitrogen content, and mean annual temperature (MAT). Furthermore, propidium monoazide (PMA)-based exclusion of extracellular DNA signals significantly altered soil prokaryotic abundance, richness, and prokaryotic community profiles, and the pool sizes of sequence-specific extracellular 16S rRNA gene amplicon fragments were significantly correlated with their respective degradation rates. This study developed a methodology for determining the overall and sequence-specific degradation rates of extracellular DNA amplicon fragments, highlighting the profound influences of extracellular DNA on soil microbial research and informing the optimization of environmental DNA technologies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/699460v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@b1b3e2org.highwire.dtl.DTLVardef@98f334org.highwire.dtl.DTLVardef@1870650org.highwire.dtl.DTLVardef@1af7105_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2026

MOV10 inhibits SADS-CoV replication by enhancing TRIM24-mediated K63-linked TRAF3 ubiquitination and this inhibition is antagonized by viral N protein

The global outbreak of SARS-CoV-2 has resulted in a renewed focus on coronaviruses with the potential for cross-species transmission and mutation risks. In particular, swine acute diarrhea syndrome coronavirus (SADS-CoV), potentially originating from intermediate horseshoe bat (Rhinolophus affinis), is a novel coronavirus that causes acute diarrhea, vomiting, and high mortality in suckling piglets. Innate immunity plays a crucial role in defending the host against invading pathogens. Previous studies have identified several host factors that inhibit SADS-CoV replication through innate immunity; however, research on SADS-CoV remains insufficient compared to that on other coronaviruses. In this study, the host factor Moloney leukemia virus 10 protein (MOV10) inhibited SADS-CoV replication by promoting interferon (IFN) production. Mechanistically, MOV10 exerted its antiviral effect primarily through its N-terminal domain, which regulated the TNF receptor-associated factor 3 (TRAF3)-mediated innate immune pathway. Specifically, we reveal that MOV10 enhanced tripartite motif-containing 24 (TRIM24)-mediated K63-linked ubiquitination of TRAF3, thereby promoting IFN production and inhibiting SADS-CoV replication. Furthermore, we identified the strategies by which SADS-CoV evaded innate immunity. The viral N protein inhibited the antiviral effect of MOV10 by disrupting interaction between MOV10 and TRAF3, and by promoting K48-linked polyubiquitination of TRAF3, leading to TRAF3 degradation via the ubiquitin-proteasome pathway. Collectively, our findings reveal the role of MOV10 in antiviral immunity and how SADS-CoV evades host immune defense.

molecular biology↗

bioRxiv2026

Discovery of potent oligopeptides for various metabolic diseases using deep learning

Artificial intelligence (AI)-based methods are increasingly critical in peptide drug discovery, but their applications are limited in a narrow scope such as antimicrobial peptides. For indications where peptide therapy inherently excels, such as metabolism, endocrinology, and tissue regeneration, AI-based pipeline for therapeutic peptide discovery is long awaited but still unmet. Here, we propose a deep learning-based pipeline, Deepeptide, capable of identifying therapeutic oligopeptides for various metabolism-related indications. Leveraging the intrinsical relationship of disease indication -- biological processes -- molecular functions, Deepeptide discovers oligopeptides with indication-ameliorating-related molecular functions as lead candidates for indication of interest. Deepeptide was applied in five representative indications of metabolism, endocrinology, and tissue regeneration: angiogenesis, lipid metabolism, osteogenesis, glucose metabolism, and anti-angiogenesis. Overall, 62% of the identified oligopeptide candidates demonstrated significant bioactivity in vitro, with most of them showing comparable potency to the first-line drugs. Notably, the heptapeptide AP7 exhibited angiogenic potency comparable to VEGF in excisional wound splinting mouse model by promoting cell migration rather than proliferation, and hexapeptide TP6 showed significant dual-efficacy against hyperlipidemia and obesity in high-fat diet mice by inhibiting lipid synthesis and regulating gut microbiota. These findings highlight the potential and generalizability of Deepeptide in therapeutic oligopeptide discovery for metabolic diseases.

bioinformatics↗

bioRxiv2025

CausalGRN: deciphering causal gene regulatory networks from single-cell CRISPR screens

Large-scale single-cell CRISPR screens with single-cell RNA-seq (scRNA-seq) readouts provide critical data to map causal gene regulatory networks (GRNs). However, translating the complex scRNA-seq outputs into reliable causal insights remains a major analytical challenge. Here we present CausalGRN, a scalable computational framework that infers causal GRNs and predicts cellular responses to unseen perturbations. CausalGRN first mitigates pervasive spurious partial correlations in sparse scRNA-seq data through a novel adaptive thresholding correction, enabling robust inference of an undirected graph. It then orients this graph using observed perturbation outcomes. The resulting directed GRN can be used to predict the downstream effects of novel perturbations via network propagation. Across both simulations and diverse experimental datasets, CausalGRN substantially outperforms existing approaches in network reconstruction accuracy and in predicting the effects of unseen perturbations, providing a principled bridge from perturbation data to causal gene regulation.

bioinformatics↗

bioRxiv2025

A VSV-vector vaccine simultaneously targeting H5N1 hemagglutinin (HA) and matrix protein 2 (M2) induces robust neutralizing and ADCC antibody responses and provides full protection against lethal H5N1 infection in a mouse model

Human (avian) influenza A viruses, especially highly pathogenic avian influenza (HPAI) viruses, pose a significant public health threat, and a multivalent vaccine is the primary prophylactic measure to control these viruses. To establish such a vaccine, we generated two multivalent vesicular stomatitis virus (VSV)-based vaccine candidates (V-EtM2e/H505 and V-EtM2e/H522) and characterized their ability to induce protective immune responses. Our results revealed that vaccine immunization in mice induced high humoral immune responses against both the HPAI hemagglutinin (HA) protein and the ectodomain of M2 (M2e) protein. Intriguingly, vaccine-immunized mouse sera exhibited highly efficient neutralizing activity against the corresponding H5 pseudovirus and mediated potent and broad antibody-dependent cellular cytotoxicity (ADCC) activity against M2e derived from human and avian influenza H5, H1, H3, and H7 viruses. Furthermore, both intranasal and intramuscular immunization provided efficient protection against HPAI H5N1 virus challenge in mice, with a 100% survival rate and a nondetectable viral load in several tissues. Notably, noninvasive mucosal (IN) delivery of V-EtM2e/H522 achieved protection equal to that of IM delivery at a 100-fold lower immunizing dose. These findings provide strong evidence for the effectiveness of a multivalent VSV-based vaccine against human (avian) influenza A viruses.

microbiology↗

bioRxiv2025

A stem cell knockout village reveals lineage rewiring and a non-canonical islet cell fate in monogenic diabetes

Genetics studies have identified a core set of regulators essential for pancreatic {beta} cell development, many of which are mutated in monogenic diabetes. However, how these mutations alter developmental trajectories to produce pathological cell states remains elusive. Here we introduce a knockout village framework that enables longitudinal scRNA-seq profiling of 79 human pluripotent stem cell mutant lines targeting 30 developmental regulators, including 15 diabetes genes, across five islet differentiation stages. We show that loss of lineage regulators impairs {beta} cell formation in a stage-specific manner and rewires developmental trajectories towards competing lineages. Notably, several monogenic diabetes gene mutations drive a shift from {beta} cells to enterochromaffin (EC)-like cells, a recently recognized non-canonical islet cell fate. These EC-like cells exhibit incomplete activation of hormone regulation programs, along with elevated neuron signatures. Leveraging the diversity of cell fate outcomes across mutants, we predicted and experimentally validated ISL1 as a key downstream effector of PDX1 and PAX6 that safeguards {beta} cell identity against an EC-like fate. Together, our findings reveal cell fate rewiring as a widespread, previously underappreciated pathological mechanism in monogenic diabetes and establish a scalable platform for uncovering developmental vulnerabilities in human genetic disorders.

developmental biology↗

bioRxiv2025

A Hybridization-Based Novel DNA Storage Technology with Rapid Read Performance

The development of traditional silicon-based microelectronic storage media has increasingly lagged behind the rapidly growing demands of contemporary data storage. DNA storage, with its ultra-high information density and long-term preservation advantages, has rapidly become a research hotspot for next-generation storage technologies. However, current mainstream DNA storage methods based on synthesis and sequencing suffer from slow read/write speeds, hindering practical applications. To address this limitation, we propose an innovative hybridization-based DNA storage scheme. Through principle validation experiments, short-text read/write and error-correction tests, and high-density multi-format file storage experiments, we verify the feasibility of this approach. The proposed method exhibits high parallelism, rapid read speeds, and robust encryption capabilities, demonstrating promising application prospects in scenarios such as confidential data storage.

synthetic biology↗

bioRxiv2025

Real-time functional connectivity-based neurofeedback of the DLPFC-amygdala pathway during threat-exposure attenuates anxiety

BackgroundAdaptive regulation of negative emotion is vital for mental health and dysregulations in this domain contribute to the major mental disorders, including anxiety and depression. On the neural level, efficient emotion regulation has been linked to functional communication between the dorsolateral prefrontal cortex (DLPFC) and the amygdala. Gaining voluntary control over this pathway may present an effective strategy for potentiating emotion regulation. ObjectiveAgainst this background, we developed a novel connectivity-based real-time fMRI (rt-fMRI) neurofeedback (NF) training that enables individuals to gain volitional control over the DLPFC-amygdala pathway during exposure to threatening stimuli. MethodsThe study employed a pre-registered, randomized, sham-controlled design with the experimental group (n = 22) receiving real-time NF information on connectivity between the right DLPFC and the amygdala during threat exposure and the sham control group (n = 23) receiving connectivity NF from a circuit not related to emotion regulation. The ability to maintain regulatory control in the absence of feedback was assessed after four NF runs. Primary outcomes included functional connectivity of the target pathway, as well as anxiety scores. ResultsThe results demonstrate that successful acquisition of self-regulation of the rDLPFC-amygdala top-down regulatory circuit in the experimental NF group facilitated attenuation of anxiety. ConclusionIn summary, our findings suggest that real-time fMRI neurofeedback (rtfMRI-NF) allows to volitionally enhance rDLPFC-amygdala connectivity, and in turn reduces negative emotional states, rendering the training a promising neurotechnology intervention for mental disorders.

neuroscience↗

bioRxiv2025

Selective Transport of Plasma-Derived Reactive Species through the Plant Aquaporin Channels: A Molecular Dynamics Study

The selective permeability of reactive oxygen and nitrogen species (RONS), generated by cold atmospheric plasma (CAP), through plant aquaporins was investigated to identify plasma-derived species capable of intracellular delivery. Using atomistic molecular dynamics and enhanced sampling methods, we quantified the free energy profiles of eight RONS (HNO3, HO2, cis-HNO2, trans-HNO2, N2O4, NO, NO2, and O3) across the PIP2;1 aquaporin channel embedded in a lipid bilayer. Hydrophobic species such as NO and O3 exhibited minimal energy barriers (~1-2 kJ{middle dot}mol-1) facilitating rapid permeation, while polar and bulky molecules like HNO3 and N2O4 encounter substantial energy barriers (>15 kJ{middle dot}mol-1), particularly near the selective region (also known as the ar/R constriction), which acts like a filter to control what can pass through the aquaporin. These results reveal that RONS permeability is governed by molecular size, polarity, and hydrogen bonding capacity. This mechanistic insight enables rational selection of CAP-generated species for enhancing plant uptake efficiency, with implications for sustainable plasma-based agricultural technologies.

biochemistry↗

bioRxiv2025

Reciprocal Homoeologous Replacement of MYB Factors Drives the Evolutionary Trade-off between Yield and Fiber Quality in Cotton

The long-standing phenotypic trade-off between Upland cotton (Gossypium hirsutum, high yield) and Sea Island cotton (G. barbadense, high quality) represents a major bottleneck in cotton breeding and industrialization. Despite rapid advances in genomics, the genomic structural variations driving the divergence of these two domestication strategies, and their subsequent impact on downstream transcriptional networks, remain unclear. This study integrates multi-tissue transcriptomic atlases spanning the full growth period with pan-genomic analyses of both Upland and Sea Island cotton, proposing a "Reciprocal Selective Retention (RSR)" strategy adopted by the two species during evolution. Transcriptomic analysis revealed that while the transcriptional chassis of the two species is highly conserved, a drastic "phase inversion" occurs during fiber development. Sea Island cotton appears to trade off for quality by specifically activating a "delayed elongation" module (at 20 DPA), whereas Upland cotton initiates a "precocious filling" program to pursue yield. Further Weighted Gene Co-expression Network Analysis (WGCNA), combined with genomic Presence/Absence Variation (PAV) analysis, identified a set of key transcription factors exhibiting a "3-vs-3" reciprocal loss pattern. Upland cotton specifically retained CRF10, WIND1, and MYB93, constructing a genetic foundation of "robust root system and strong regeneration" to support high yield. Conversely, Sea Island cotton specifically retained MYB111 and ERF105/017 to maintain long-staple characteristics and environmental buffering. Whole-genome structural variation and microsynteny analyses confirmed that these differences stem from asymmetric physical deletions (e.g., a 5 kb deletion in MYB111) or fragment sequence collapse (e.g., a 15.9 kb sequence divergence in MYB93) on homologous chromosomes. The RSR model proposed in this study not only offers a novel insight into the genetic roots of the negative correlation between yield and quality but also provides clear genomic targets for precision improvement using gene-editing technologies such as CRISPR.

genomics↗

bioRxiv2025

Engineering chimeric DNA polymerases for DNA movable type storage

DNA-based information storage offers a promising alternative to conventional media due to its high density, long-term stability, and low energy requirements. However, its application remains hindered by synthesis costs, limited sequence length and poor scalability. DNA polymerase is a critical enzymatic tool in the DNA storage systems by enabling high-fidelity data writing and targeted sequence amplification. In this study, we engineered chimeric DNA polymerases by fusing the high-fidelity 9{degrees}N DNA polymerase with double-stranded DNA binding proteins derived from thermophilic archaea. These fusions significantly enhanced processivity, thermal stability, and salt tolerance by stabilizing enzyme-template interactions, mimicking sliding clamps while preserving catalytic efficiency. Leveraging these properties, we demonstrated precise file retrieval from a mixed oligonucleotide pool using orthogonal barcode primers. Compared with wild-type 9{degrees}N, the chimeric polymerases, particularly PLS, exhibited reduced substitution error rates and improved read accuracy. We then applied these enzymes to a DNA movable type storage system, where prefabricated DNA modules were assembled into encoding blocks. Using engineered polymerases, these blocks were recombined to enable flexible data rewriting without de novo DNA synthesis. Moreover, a multi-enzyme assembly strategy enabled the construction of kilobase-scale DNA sequences encoding a classical Chinese poem, achieving complete data recovery. All assembled fragments remained stable in E. coli over 100 generations, exhibiting the potential for in vivo storage. Collectively, our findings demonstrated the role of engineered DNA polymerases for DNA-based information storage. Moreover, this system reduced synthesis demands, supported scalable rewriting, and ensured long-term preservation, offering a practical route to sustainable, high-fidelity DNA data storage.

synthetic biology↗

bioRxiv2025

Mechanisms of tumor persistence in metastatic melanoma following successful immunotherapy

Tumor dormancy is thought to enable cancer recurrence, but the settings and mechanisms of dormancy in patients are poorly characterized. Both immunogenic tumor mass dormancy, involving continued tumor cell proliferation and balanced immune-mediated cell death, and cell-level quiescence have been observed in preclinical models. Here, we demonstrate the existence of mass dormancy rather than quiescence in long-term stable residual lesions in melanoma patients treated with immune checkpoint inhibitors (ICI). In a large stable lesion subjected to detailed spatial profiling, the proportion of proliferating tumor cells is similar to that in site-matched tumors from patients progressing after ICI. Residual stable lesions from other patients, judged to contain only scar tissue upon clinical pathology review, also contained nests of dividing tumor cells surrounded by active immune cells. These findings demonstrate the presence of viable tumor cells and mass dormancy in persistent stable lesions, a finding with implications for disease monitoring and management.

cancer biology↗

bioRxiv2025

Identification of Vector Organisms and Their Carried Pathogens by Metagenomic Sequencing

Vector surveillance is vital for public health, yet traditional methods often face limitations. This study assessed the use of metagenomic sequencing for analyzing mosquitoes, cockroaches, flies, and rodents from Zhongshan, China. The results revealed a high concordance between metagenomic and Sanger sequencing for species identification (Kappa = 0.667, P = 0.011). Metagenomic analysis identified vector-specific dominant bacteria, including Wolbachia in mosquitoes, Blattabacterium sp. in cockroaches, Bartonella tribocorum and Leptospira interrogans in rodents, and Vagococcus teuberi in flies. It also detected numerous classical pathogens, such as Enterococcus faecalis, L. interrogans, and Klebsiella pneumoniae. Among the identified fungi and viruses, 19 were human pathogens, while seven posed a threat to agriculture, notably Pepper mild mottle virus and Tomato brown rugose fruit virus. These findings systematically characterize the microbial communities associated with various vectors, highlight the potential of metagenomics for broad pathogen screening, and underscore its utility in large-scale vector surveillance and public health protection. ImportanceVectors are major carriers of numerous diseases and present risks fot cross-border transmission. Existing detection methods for vectors and their pathogens remain inefficient, insensitive, and prone to difficulties in species identification. Despite extensive efforts in vector identification, the potential threats posed by their associated pathogens remain unclear, demonstrating the need for more effective diagnostic strategies. Metagenomic sequencing offers a promising solution to this challenge. In this study, we applied metagenomic sequencing to vectors collected from urban and port areas in Zhongshan, China, to evaluate its efficacy in pathogen detection. Overall, our work contributes to a better understanding of the public health risks posed by vector-borne pathogens.

microbiology↗

bioRxiv2025

Dynamic alterations of DNA methylation and transcriptome in adaptation to and recovery from the space environment

Space exploration presents tremendous health challenges. Here, we report time series of multi-omic and phenotypic profiles of seventeen astronauts from six China Manned Space missions with continuous spaceflight durations ranging from 13 to 180 days. We revealed a key role of DNA methylation regulation in reshaping gene expression patterns to adapt to the space environment. Long-duration spaceflight showed more alterations in epigenetic modifications correlated with alternative splicing and protein acetylation. During recovery, an "overrange rebound" phenomenon was observed, furthermore, a mathematical model was established to describe this implying important phenomenon. Moreover, we revealed the correlations between molecular alterations and phenotypic changes such as coagulation activation and bone intensity loss. Additionally, we performed ground-based simulation experiments to estimate the impacts of individual stressors in the space environment on DNA methylation. In summary, our study highlights the importance and complexity of epigenetic regulation in adaptation to and recovery from the space environment.

genomics↗