Biomedical subjects

Kun Wang

Publications and source records attributed to Kun Wang.

9 recordsLinked to original sources

PubMed2026

Evolutionary patterns and repeated adaptive strategies of deep-sea anemones.

Sea anemones occupy the full depth range of the oceans, yet their evolutionary patterns and adaptive strategies to the enigmatic deep sea have remained contentious and poorly resolved. Here, we assemble genomes (n = 13) and transcriptomes for 15 species collected between 432 and 6,000 m and integrate them with publicly available actiniarian data. We find support for a shallow-water origin of Actiniaria through a framework that emphasizes genome-scale changes associated with habitat transitions. Most strikingly, these changes include repeated dismantling of the circadian toolkit across deep-sea lineages. In addition to convergent gene losses in photo- and temperature-regulatory genes, we find that some deep-sea lineages have experienced recurrent loss or pseudogenization of key meiotic genes (e.g., Meiosin, Ythdc2, Spo11, and Mlh3), suggesting reduced meiotic capacity in some lineages. Despite this extensive genomic erosion, deep-sea anemones exhibit molecular tuning: specific amino acid substitutions improve enzyme performance under low-temperature conditions relevant to the deep sea, while selective expansions of gene families related to neural excitability, membrane systems, and other functions may help maintain physiological performance in this environment. Functional assays in yeast indicate enhanced performance of the deep-sea variants at 4°C. These results define a "loss-optimization-innovation" triad that underlies bathymetric adaptations and may apply to other deep-sea fauna worldwide.

Actiniaria↗

PubMed2026

Abalone genomics reveals an ancient asymmetry axis and the multifunctionality of the mantle.

Gastropod diversification represents one of the most spectacular evolutionary radiations, underpinned by a fundamentally asymmetric body plan and diverse pigmentation patterns. To understand the genetic underpinnings of these cardinal traits, we constructed a chromosome-level genome assembly for the rainbow abalone, Haliotis iris. Integrating comparative genomics, histoembryology, and molecular assays, we identify a conserved regulatory association between the long non-coding RNA lncRNA1 and pitx that is associated with asymmetric mantle development. In H. iris, this association is supported by chromatin-contact evidence and exploratory data suggesting a possible miRNA-associated post-transcriptional component. Furthermore, we identify a wnt-mitf-tyr framework for melanogenesis and show that the mantle is the primary site of melanin synthesis. Concurrently, we identify mantle-enriched prestin genes that are vibration-responsive, consistent with a possible sensory specialization of the mantle. These findings provide molecular insight into asymmetry, pigmentation, and mantle multifunctionality in gastropods.

Animals↗

PubMed2026

Integrated multi-omics analyses identify an RAS-SLC11A2-associated molecular framework linking iron metabolism with PCOS-related cardiometabolic risk.

INTRODUCTION: PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside. METHODS: Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and in vitro functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM. RESULTS: SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation. CONCLUSION: This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.

Humans↗

PubMed2026

Cross-kingdom genomic variation in chicken gut microbiomes: insights from China's diverse local breeds.

BACKGROUND: The gut microbiome possesses substantial genetic diversity that supports microbial adaptation, but the genomic variation patterns across its prokaryotic and viral populations remain incompletely characterized. RESULTS: Through integrated metagenomic and metatranscriptomic analysis of ten indigenous chicken breeds from China, we recovered 1527 representative prokaryotic MAGs, 37,555 representative DNA viral contigs, and 1867 representative RNA viral contigs (primarily comprising Bacillota/Bacteroidota, Uroviricota, and Lenarviricota/Pisuviricota, respectively). By integrating complementary short-read and long-read metagenomics with metatranscriptomics, we identified structural variants (SVs) and single-nucleotide variants (SNVs) in these cross-kingdom genomes. Positive SV-SNV density correlations occurred consistently across all microbial groups, indicating coordinated mutational processes. DNA viruses exhibited the highest variant prevalence (86.9% SNVs, 47.7% SVs), with temperate phages accumulating significantly more variants than virulent phages. Functionally, prokaryotic variants accumulated in carbohydrate metabolism and amino acid metabolism, while viral variants demonstrated broad metabolic hijacking. Horizontal gene transfer (HGT) was characterized by a strong virus-associated signature (69.40% of 536 events) and marked by an asymmetric pattern, with phage-to-bacteria (P-to-B) flow alone constituting 37.50% of all events. Random forest analysis revealed a strong bidirectional predictive relationship between SV and SNV densities across prokaryotic, DNA viral, and RNA viral populations, suggesting coupled genomic instability. Niche breadth emerged as a major driver of SNVs across kingdoms and was positively correlated with variant density. In prokaryotes, HGT events significantly shaped variant patterns. For viruses, genomic GC content was an important factor and consistently showed a negative correlation with SNV density in both DNA and RNA viruses. CONCLUSIONS: These findings demonstrate that coordinated mutational processes and kingdom-specific intrinsic factors drive genomic variation, with viruses serving as key genetic exchange vectors in chicken gut ecosystems. Video Abstract.

Animals↗

PubMed2026

Host genetic regulation of xylem-resident Pseudomonas enhances cucumber growth.

BACKGROUND: Although endophytic microorganisms play a critical role in plant growth and stress resilience, the genetic basis underlying host selection of beneficial microbiota-particularly within the xylem-remains poorly understood. Cucumber (Cucumis sativus), as a crop model with a well-developed system for studying vascular biology, offers a valuable system to investigate the host genetic determinants of xylem microbiome assembly. RESULTS: By conducting population-level microbiome profiling across 109 cucumber accessions, we identified a conserved xylem microbiota dominated by Proteobacteria. Within this community, 20 core amplicon sequence variants (ASVs) were consistently present in xylem sap. Genome-wide association mapping identified a host genetic locus, CsXPR1, which encodes a tetratricopeptide repeat protein that regulates the abundance of the dominant xylem-colonized Pseudomonas ASV_4. Colonization patterns of ASV_4 varied across host genotypes and were correlated with CsXPR1 expression levels, suggesting a precision genetic regulation of bacterial entry into vascular tissues. Pseudomonas fulva strain 220, with 97% 16S rRNA gene identity with ASV_4, could colonize in cucumber xylem by inoculation of either roots or leaves. Genome analysis and plate assays revealed the biosynthesis of indole-3-acetic acid (IAA), solubilization of phosphate, and a range of plant beneficial traits in strain 220. Inoculation with strain 220 significantly enhanced growth in cucumber, but only in CsXPR1 haplotype that exhibited high gene expression and higher recruitment capacity of the strain. These benefits included notable increases in plant height (38%), stem diameter (36%), leaf area (61%), fresh and dry weight (51% and 85%, respectively), and a 4.57-fold increase in 4-methyleneglutamine content within the xylem sap. CONCLUSION: Our findings reveal a complete "gene-to-function" pathway where the host gene CsXPR1 mediates a genotype-dependent growth promotion. It achieves this by regulating the xylem colonization of a beneficial bacterium, Pseudomonas fulva, which in turn enhances plant growth by enriching the xylem sap with the key metabolite 4-methyleneglutamine. Video Abstract.

Cucumis sativus↗

PubMed2026

Drug-resistant genes, virulence characteristics, and molecular typing of clindamycin-resistant Streptococcus agalactiae in late pregnancy.

BACKGROUND: Streptococcus agalactiae increases the risk of adverse pregnancy outcomes and neonatal infections. Clindamycin is a key alternative for intrapartum prophylaxis in penicillin-allergic women, but the prevalence of clindamycin-resistant S. agalactiae is increasing, posing a significant clinical challenge. METHODS: A total of 178 strains isolated from tertiary hospitals in Jinan and Qingdao, Shandong Province, China, were characterized using antimicrobial susceptibility testing, whole-genome sequencing, multilocus sequence typing, serotyping, and analysis of resistance and virulence genes. RESULTS: All strains were susceptible to penicillin, ampicillin, linezolid, vancomycin, and tigecycline. In contrast, resistance rates to erythromycin, levofloxacin, and tetracycline were 95.5%, 60.1%, and 56.7%, respectively. Six serotypes and 15 sequence types belonging to eight clonal complexes were identified. Notable regional differences were observed. The Ib-ST10-CC12 lineage dominated in Jinan, whereas V-ST529-CC327 was predominant in Qingdao. The resistance gene mreA was ubiquitous (100%), followed by ermB (80.3%). The key virulence genes cylE, hylB, and pavA, were detected in all strains. fbsA (99.4%), the alpha protein family (98.9%), cfb (98.3%), the Pilus Island gene cluster (94.9%), and lmb (92.7%) were also highly prevalent. The two major clindamycin resistance genes, erm and lnuB, exhibited distinctly different enrichment patterns among S. agalactiae clonal complexes, despite a certain overlap in CC19 and CC327. Specifically, erm was significantly enriched in CC12 (serotype Ib), CC19 (III/V), and CC327 (III/V). In contrast, lnuB was predominantly restricted to CC19 and CC327, where it defined a unique phylogenetic subcluster. Significant differences in resistance and virulence gene profiles were observed across different clonal complexes. CONCLUSION: Clindamycin-resistant S. agalactiae in late-pregnancy women in Shandong Province, China exhibits a broad resistance spectrum, diverse molecular types, and significant regional heterogeneity. These findings underscore the need for continued surveillance and region-specific strategies for preventing neonatal S. agalactiae infections.

Humans↗

PubMed2025

CCRR: a user-friendly platform for analyzing complex chromosomal rearrangements in tumors.

SUMMARY: Complex chromosomal rearrangements in tumors involve intricate genomic alterations that significantly affect gene function and contribute to cancer development. Identifying these events is crucial for cancer research but is often challenging due to the complexity and limitations of existing tools. We developed the Complex Chromosomal Rearrangements Resolver (CCRR), a comprehensive, reproducible, and user-friendly platform for analyzing complex rearrangements in tumors. CCRR integrates multiple SV and CNV detection tools within a Docker container environment, simplifying installation and configuration. It can be easily deployed, automating the execution and merging of results, providing high-confidence consensus SV and CNV calls, allowing researchers to efficiently analyze complex chromosomal rearrangements in tumors without extensive bioinformatics expertise. CCRR also includes a web server for one-click analysis and customized visualization. AVAILABILITY AND IMPLEMENTATION: The CCRR platform is freely available at https://www.ccrr.life. Source code and executables can be accessed at https://github.com/laslk/CCRR. An archived version is available at Zenodo: https://doi.org/10.5281/zenodo.15386513.

Software↗

PubMed2025

Genomic and phenotypic insights into ST164 blaNDM-1-positive Acinetobacter baumannii from intestinal colonization in China.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a critical global threat, especially in ICUs. Yet, reports on ST164 CRAB harboring blaNDM-1 remain scarce. This study investigates two clinical CRAB isolates, L4773hy and L4796hy, derived from intestinal colonization in Hangzhou, China, focusing on their phenotypic and genomic characteristics as well as the broader transmission of ST164 A. baumannii. METHODS: Bacterial identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) mass spectrometry. Antimicrobial susceptibility was assessed via agar and broth microdilution. Whole-genome sequencing employed Illumina NovaSeq 6000 and Oxford Nanopore platforms. Resistance genes, insertion elements, transposons, and integrons were detected using ResFinder, PlasmidFinder, VFDB, ISFinder, pdifFinder, and IntegronFinder. Strains were typed by MLST, and a phylogenetic tree was constructed with kSNP3.0. Genetic environment diagrams were generated using Easyfig 2.2.5. RESULTS: Two blaNDM-1-carrying A. baumannii isolates exhibiting extensive resistance to carbapenems, cephalosporins, and fluoroquinolones. Whole-genome sequencing and genetic environment analysis revealed the presence of a conserved structural sequence (ISAba14-ISAba14-aphA-ISAba125-blaNDM-1-bleMBL) on their chromosomes. Phylogenetic and clonal dissemination analysis showed that ST164 CRAB is primarily distributed in China and exhibits clonal spread. Pathogenicity studies indicated that blaNDM-1-positive ST164 strains have enhanced survival under immune pressure but do not display increased virulence in infection models. CONCLUSION: This study provides the genomic and phenotypic characterization of intestinally colonized ST164 blaNDM-1 positive CRAB in Hangzhou, China. The elucidation of the genetic environment of blaNDM-1 further confirms the clonal dissemination of ST164 isolates, highlighting the importance of enhanced surveillance and infection control measures to mitigate the spread of these multidrug-resistant pathogens.

Acinetobacter baumannii↗

PubMed2024

Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration.

As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocalization of genomic DNA, which acted as a powerful driver of cGAS/STING axis-dependent inflammatory phenotype acquisition during NP cell senescence. Mechanistically, disassembly of the ATR-tripartite motif-containing 56 (ATR-TRIM56) complex with the enzymatic liberation of ubiquitin-specific peptidase 5 (USP5) and TRIM25 drove changes in ATR ubiquitination, with ATR switching from K63- to K48-linked modification, c thereby promoting ubiquitin-proteasome-dependent dynamic instability of ATR protein during NP cell senescence progression. Importantly, an engineered extracellular vesicle-based strategy for delivering ATR-overexpressing plasmid cargo efficiently diminished DNA damage-associated NP cell senescence and substantially mitigated IVDD progression, indicating promising targets and effective approaches to ameliorate the chronic pain and disabling effects of IVDD.

Humans↗