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Xin Huang

Publications and source records attributed to Xin Huang.

At least 19 recordsLinked to original sources
PubMed2026

Functional convergence of regulatory regions provides vital insights into mammalian gliding adaptation.

Uncovering the key genetic basis of complex phenotypic convergence in distantly related species has been a long-standing focus in evolutionary biology and genetics, and the convergent evolution of gliding in mammals offers a valuable opportunity to address this question. Here, we investigated the genomic basis of convergent evolution of gliding in mammals by analyzing both protein-coding genes and conserved non-coding elements (CNEs). We first de novo assembled and annotated two chromosome-level genomes of gliding mammals, the red and white giant flying squirrel (Petaurista alborufus) and sugar gliders (Petaurus breviceps), and conducted comprehensive comparative genomic analysis combined with another gliding mammal, the Sunda flying lemur (Galeopterus variegatus) and 14 background species. We found that the convergent evolution of protein-coding genes provided relatively limited but functionally relevant evidence linked to gliding phenotypes. By contrast, we found that gliding-accelerated CNEs (GACNEs) cluster near functionally equivalent genes and frequently aggregate into highly diverged yet functionally convergent hotspot regions. Across the three gliding lineages, both GACNEs and hotspot GACNEs show strong convergence in their functional enrichment profiles, suggesting a broad genetic basis underlying the convergent gliding phenotype. Furthermore, we identified 72 core transcription factors underpinning the genetic basis of gliding convergence, including EMX2 and ZFHX3, potentially involved in multiple aspects of gliding adaptation. Our study highlights the role of functional convergence in regulatory regions as a key mechanism in mammalian gliding convergence, offering valuable insights and strategies for uncovering the genetic basis of complex convergent traits, thereby advancing understanding of the molecular basis of convergent traits.

Petaurista alborufus↗
PubMed2026

High-level terpene production via a novel Actinomycetota-derived MVA pathway in E. coli.

The heterologous production of terpene in microbial hosts is often limited by inefficient and unstable pathway expression, creating a major bottleneck for industrial-scale synthesis. While E. coli as a chassis offers significant advantages, such as rapid growth, ease of cultivation, and genetic tractability. Its endogenous supply of terpenoid precursors remains a critical constraint, fundamentally restricting high-yield production. To address this challenge, we developed a genomically integrated Mevalonate (MVA) pathway from Actinomycetota in E. coli BL21(DE3) to enhance terpene precursor supply. Our approach began with an in silico multi-layer global genome mining analysis of 25,261 Actinomycetota genomes to identify a series of MVA pathway enzymes with potentially high catalytic efficiency, created a high-efficiency chassis E. coli MVA platform (ecMVA-1 and ecMVA-2) for terpene precursor synthesis. Its functionality was validated by testing eight distinct TSs. Among them, the fermentation of artemisinin precursor amorphadiene using a 5-liter bioreactor yielded 947.80 mg/L. These results indicated that E. coli (MVA) is well-suited for TS studies in the laboratory as well as holding significant promise for industrial applications. In addition, this in silico approach offers a new perspective for metabolic engineering and provides potential reservoir of diverse chassis for the industrial production of terpenoid-derived compounds.

Actinomycetota↗
PubMed2026

Lineage structure and penicillin-binding protein variability in clinical Streptococcus pneumoniae isolates from Southwest China exhibiting reduced susceptibility to penicillin.

BACKGROUND: Reduced susceptibility to penicillin in Streptococcus pneumoniae is mediated primarily by alterations in penicillin-binding proteins (PBPs) and often coexists with multidrug resistance within successful lineages. The region-specific genomic characterization of clinically relevant pneumococci with reduced penicillin susceptibility in Southwest China remains limited. METHODS: We performed whole-genome sequencing of 204 clinical S. pneumoniae isolates collected from five institutions in Southwest China (2018-2022) that met our operational screening definition of reduced susceptibility to penicillin (PEN MIC ≥0.12 μg/mL). Molecular serotypes, MLST types, and Global Pneumococcal Sequence Clusters (GPSCs) were assigned; virulence and antimicrobial resistance determinants were profiled; and a core genome phylogeny was reconstructed with international contextualization through the use of PubMLST genomes meeting the same MIC criterion. Amino acid variability in PBP1a/PBP2b/PBP2x was quantified using TIGR4 numbering, and highly variable noncatalytic residues located within 15 Å of catalytic motifs were prioritized via structure-guided screening. RESULTS: The isolates showed a high burden of resistance to non-β-lactam antibiotics (erythromycin, 98.5%; tetracycline, 82.8%; trimethoprim-sulfamethoxazole, 64.7%), while fluoroquinolone susceptibility was largely preserved (≥97%), and vancomycin/linezolid resistance was not detected. Twenty-seven serotypes were identified, among which 19F (23.5%) and 19A (14.2%) were dominant, and the estimated PCV13 coverage was 69.6%. GPSC1 was the dominant lineage (36.8%), and the lineage composition among our isolates differed markedly from those in the PubMLST-USA and PubMLST-Thailand subsets. Virulence and resistance gene carriage differed markedly between GPSC1 and non-GPSC1 isolates, with enrichment of pilus operons, mef(A)/msr(D), and folA/folP in GPSC1. PBP variations were clustered in transpeptidase domains and motif-adjacent regions while essential catalytic residues were conserved; with the structure-guided filter, 12, 11, and 11 motif-proximal noncatalytic candidate sites were prioritized in PBP1a, PBP2b, and PBP2x, respectively. CONCLUSION: Clinical S. pneumoniae isolates with reduced penicillin susceptibility collected in Southwest China demonstrated resistance and accessory gene profiles that were strongly structured by a GPSC-defined lineage background. Our site-resolved, structure-guided PBP analysis provides a regional PBP variability landscape and a compact set of recurrent motif-proximal candidate substitutions to support surveillance and downstream functional validation.

Streptococcus pneumoniae↗
PubMed2026

Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages.

Genetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers' genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology.

Humans↗
PubMed2026

Cardiometabolic Multimorbidity Increases the Risk of Hip Fracture: A Longitudinal Cohort Study Based on CHARLS.

BACKGROUND: Cardiometabolic Multimorbidity (CMM) is defined as the co-occurrence of two or more conditions among heart disease, diabetes mellitus, stroke, and hypertension. Previous studies have shown associations between cardiometabolic diseases and fragility fractures; however, the relationship between CMM and hip fractures remains unclear in the Chinese population. This study therefore aims to investigate this association in a Chinese cohort to inform fracture prevention strategies. METHODS: This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) collected from 2011 to 2020. Participants from the 2011 baseline survey cohort were initially included. Subsequently, individuals were sequentially excluded if they were under 45 years of age, had incomplete baseline CMM information, had a history of hip fracture, lost to follow-up, or had missing data on confounders. Kaplan-Meier survival analysis, Cox proportional hazards regression, subgroup analyses, and sensitivity analyses were performed to evaluate the association between CMM and the risk of hip fracture. RESULTS: A total of 6314 participants aged 45 years and older were included, of whom 544 had CMM. Over a 9-year follow-up period, 287 incident hip fractures (4.55%) were identified. Among these, 36 participants had been diagnosed with CMM at baseline, whereas 251 had not. The incidence of hip fracture was significantly higher in participants with CMM than in those without CMM (13% vs. 8%, p = 0.015). After full adjustment for confounders, multivariable Cox regression showed that CMM was associated with a 70% increased risk of hip fracture (HR = 1.70, 95% CI: 1.318-2.47; p = 0.005). Subgroup analyses indicated that age and history of falls were significant effect modifiers. The association between CMM and hip fracture was more pronounced in participants under 60 years old (P for interaction = 0.048) and those with a history of falls (P for interaction = 0.014). CONCLUSION: These findings suggest that CMM increases the risk of hip fracture, particularly among relatively younger individuals and those with a history of falls.

Humans↗
PubMed2026

HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials.

BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peripherally restricted kappa-opioid receptor (KOR) agonist that selectively targets visceral pain pathways enriched with KORs, may provide adequate analgesia without systemic adverse events. METHODS: We conducted a pooled post-hoc analysis of data from two phase III, multicenter, triple-blinded, randomized controlled trials (Study 301, HSK21542 vs placebo; Study 303, HSK21542 vs tramadol vs placebo). Eligible patients undergoing elective gynecological surgery were included. The primary outcome was the summed pain-intensity difference over 12 and 24 hours (SPID 12h and SPID 24h ). Secondary outcomes were pain-relief quality (proportion of patients relieved from severe pain with a pain numerical rating score &#x2264; 3 between 0 and 24 hours) and rescue-analgesic requirements (number of doses and time to first rescue analgesic). Adverse events were also assessed. RESULTS: A total of 370 patients were analyzed: 150 received HSK21542, 139 received a placebo, and 81 received tramadol. After inverse probability of treatment weighting (IPTW) adjustment, baseline characteristics were well-balanced across treatment groups (all standardized mean differences [SMD] <0.1; see Table 1 for 95% CIs). HSK21542 produced greater reductions in pain intensity over 12 and 24 hours than placebo (least-squares mean differences -8.1 and -16.3 for SPID 12h and SPID 24h , respectively. Both P < .001) and no statistically significant difference was observed between HSK21542 and tramadol ( P > .05). Significantly more patients in the HSK21542 group were relieved from severe pain at 0 to 12 hours (92.7% vs 82.7%, P < .001) and required fewer rescue doses at 0 to 12 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) and 0 to 24 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) than those in the placebo group, whereas no significant differences with tramadol both in 0 to 12 and 0 to 24 hours. HSK21542 was also associated with significantly lower incidences of nausea (24.7% vs 66.7%) and vomiting (21.3% vs 60.5%) than tramadol. Only one case of dizziness occurred in the tramadol group. CONCLUSIONS: HSK21542 could provide adequate postoperative analgesia with few adverse events in patients undergoing gynecological surgery.

Humans↗
PubMed2025

Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment.

Polycomb domains safeguard cell identity by maintaining lineage-specific chromatin states enriched in repressive histone modifications, preserving the epigenetic memory of cell lineages. While Polycomb Repressive Complex 2 (PRC2) can re-establish its occupancy after perturbation, the mechanisms that guide de novo Polycomb recruitment remain unclear. To address this, we engineered an auxin-inducible degradation system to reversibly deplete and reintroduce the endogenous PRC2 core subunit Suz12 in mouse embryonic stem cells (mESCs). Genome-wide profiling at an early recovery time point revealed ~1,100 PRC2 nucleation sites, characterized by rapid Suz12 and histone H3K27me3 re-accumulation with strong signal, with minimal impact on gene expression. These sites were significantly enriched at bivalent promoters, coinciding with unmethylated CpG islands and chromatin states associated with developmental regulation, and were largely conserved in differentiated cells. Motif analysis identified G/C-rich DNA sequences associated with E2F and zinc-finger proteins, alongside strong co-occupancy with MTF2 and JARID2, two PRC2 cofactors previously implicated in Polycomb targeting. Notably, a subset of nucleation sites overlapped with long-range chromatin interaction anchors in histone H3K27me3 HiChIP datasets. These findings reveal that PRC2 de novo nucleation sites are associated with a combination of chromatin states, DNA sequence features, cofactor co-occupancy and spatial genome organization, suggesting that epigenetic memory can be re-established through defined genomic and chromatin features.

Epigenetic memory↗
PubMed2025

Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays.

Single-cell sequencing technologies have advanced our understanding of cellular heterogeneity and biological complexity. However, existing methods face limitations in throughput, capture uniformity, cell size flexibility, and technical extensibility. We present Stereo-cell, a spatial enhanced-resolution single-cell sequencing platform based on high-density DNA nanoball (DNB)-patterned arrays, which enables scalable and unbiased cell capture at a wide input range and supports high-fidelity transcriptome profiling. Stereo-cell further allows integration with imaging-based modalities and multiomics strategies, including immunofluorescence and epitope profiling. This platform is also compatible with profiling extracellular vesicles, microstructures, and large cells, whereas its spatial resolution facilitates in situ analysis of cell-cell interactions, cellular microenvironments, and subcellular transcript localization. Together, Stereo-cell provides a flexible framework for expanding single-cell research applications.

Animals↗
PubMed2025

Accessible, realistic genome simulation with selection using stdpopsim.

Selection is a fundamental evolutionary force that shapes patterns of genetic variation across species. However, simulations incorporating realistic selection along heterogeneous genomes in complex demographic histories are challenging, limiting our ability to benchmark statistical methods aimed at detecting selection and to explore theoretical predictions. stdpopsim is a community-maintained simulation library that already provides an extensive catalog of species-specific population genetic models. Here we present a major extension to the stdpopsim framework that enables simulation of various modes of selection, including background selection, selective sweeps, and arbitrary distributions of fitness effects (DFE) acting on annotated subsets of the genome (for instance, exons). This extension maintains stdpopsim's core principles of reproducibility and accessibility while adding support for species-specific genomic annotations and published DFE estimates. We demonstrate the utility of this framework by comparing methods for demographic inference, DFE estimation, and selective sweep detection across several species and scenarios. Our results demonstrate the robustness of demographic inference methods to selection on linked sites, reveal the sensitivity of DFE-inference methods to model assumptions, and show how genomic features, like recombination rate and functional sequence density, influence power to detect selective sweeps. This extension to stdpopsim provides a powerful new resource for the population genetics community to explore the interplay between selection and other evolutionary forces in a reproducible, user-friendly framework.

Journal Article↗
PubMed2025

Impaired natural killer cell maturation in lung adenocarcinoma driven by FABP4 and SPON2 downregulation through disrupted lipid metabolism.

BACKGROUND: Although natural killer (NK) cells play a crucial role in antitumor immunity, the metabolic changes driving their dysfunction in lung adenocarcinoma remain poorly understood. This study investigates how these metabolic modifications impact NK cell function within the lung adenocarcinoma microenvironment. METHODS: A total of 13 pairs of lung adenocarcinoma samples were obtained from The Cancer Genome Atlas. Differential gene expression, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and single-cell metabolic quantification analyses were used to characterize the transcriptomic, pathway, and metabolic signatures of NK cells. The developmental trajectory was reconstructed via pseudotime analysis. The fatty acid-binding protein 4 (FABP4) and spondin2 (SPON2) expression was examined using immunofluorescence (IF) and immunohistochemistry (IHC) in patients with lung adenocarcinoma. In NK cells with FABP4 downregulation, FABP4 function was analyzed using antibody-independent cell-mediated cytotoxicity assays, flow cytometry (FCM), and liquid chromatography-mass spectrometry. RESULTS: The number of NK cells was significantly decreased in the lung adenocarcinoma microenvironment. FABP4 and SPON2 expression was significantly lower in NK cells within tumor tissues than in the adjacent tissues. FABP4 expression was significantly lower in tumor tissues than in the adjacent tissues, whereas no significant difference in SPON2 expression was observed. The cytotoxic function of NK cells with decreased FABP4 levels was impaired. Non-targeted lipid metabolism analysis indicated that differentially expressed lipids in NK cells with low FABP4 levels were functionally enriched in the glycerophospholipid metabolism pathway compared to those in normal NK cells. CONCLUSIONS: The study findings present new evidence showing that low FABP4 and SPON2 gene expression may impair NK cell maturity by affecting lipid metabolism in lung adenocarcinoma. These results provide a new perspective on restoring immune function in patients with lung cancer.

FABP4↗
PubMed2025

Mutation of strigolactone biosynthetic gene DWARF 17 impairs the responses of rice tillering to N supply.

Tiller number is one important parameter for rice yield and is influenced by both strigolactone (SL) and nitrogen (N). However, how SL and N interact to regulate the tiller outgrowth in rice is unclear. In this study, we isolated a multi-tillering mutant, tin, from an ethyl methanesulfonate (EMS)-mutagenized population of Wuyunjing 7, a japonica cultivar. The tin mutant exhibited low sensitivity to varying N concentrations during the tiller development. Through bulk segregation analysis (BSA), we identified a missense mutation located in the exon of DWARF 17 (D17), a key gene involved in SL biosynthesis. Complementation experiments confirmed that D17 is responsible for the tin tiller phenotype, and exogenous application of the SL analogue GR24 restored the tiller response of tin to N. Transcriptome analysis further revealed that D17 and SL regulate the tiller response to N by modulating the expression of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes and ammonium transporter genes. These findings elucidate the mechanism by which SL and N coordinate to regulate rice tillering growth, providing valuable insights for optimizing rice plant architecture to enhance yield potential.

Oryza↗
PubMed2007

Telluroxides exhibit hydrolysis capacity.

It has long been known that tellurium compounds are rather toxic to living organisms, and tellurium has not been found in natural biomacromolecules to date. The principles of telluride toxicity in biological processes are still controversial partly because of the lack of information on the biochemical features of tellurium. In this contribution, we report our finding for the first time that telluroxides exhibit hydrolysis capacity. For instance, 6,6'-telluroxy-bis(6-deoxy-beta-cyclodextrin) acts as a hydrolase mimic and shows a significant rate acceleration of 106,000 for the hydrolysis of 4,4'-dinitrodiphenyl carbonate.

Journal Article↗
PubMed2007

A liquid chromatography-mass spectrometry method for the quantitation of aristololactam-I in rat plasma.

A sensitive method with liquid chromatography-electrospray ionization mass spectrometry has been developed and validated for the determination of aristololactam-I in rat plasma after oral administration of aristolochic acid-I using finesteride as the internal standard. Chromatographic separation was achieved on a Lichrospher C(18) column using methanol:0.05% acetic acid in water (71:29, v/v) as a mobile phase delivered at a flow rate of 1 mL/min. The assay was linear for aristololactam-I over the range 0.3-300 ng/mL. The analysis of quality control samples demonstrated precision with coefficient of variation less than 20% (n = 5). Absolute recovery of aristololactam-I was 90.4-97.3%. The LC-MS method for the determination of aristololactam-I is sensitive, specific and can be used to investigate the toxicokinetics of aristololactam-I.

Animals↗
PubMed2007

Relationship between FRA11F and 11q13 gene amplification in oral cancer.

Common fragile sites (CFS) are nonstaining gaps or breaks in chromosomes that are expressed under conditions inducing replicative stress. CFS have been suggested to play a role in epithelial cancers by their association with loss of heterozygosity, loss of gene expression, and/or gene amplification in the form of homogeneously staining regions (hsrs). In oral squamous-cell carcinomas (OSCC), amplification of chromosomal band 11q13 occurs in the form of an hsr. We suggested previously that CFS flanking 11q13 may be susceptible to breakage induced by tobacco or other carcinogens and/or human papillomavirus, promoting formation of the 11q13 amplicon. Examination of OSCC cell lines with 11q13 amplification using fluorescence in situ hybridization showed loss of FRA11F sequences, whereas cell lines without 11q13 amplification displayed an intact FRA11F site. Cell lines with more complex 11q rearrangements expressed FRA11F in the form of an inverted duplication, characteristic of breakage-fusion-bridge cycles. Our findings suggest that gene amplification involving chromosomal band 11q13 in OSCC may be initiated by breakage at FRA11F.

Carcinoma, Squamous Cell↗
PubMed2006

A bacterial protein enhances the release and efficacy of liposomal cancer drugs.

Clostridium novyi-NT is an anaerobic bacterium that can infect hypoxic regions within experimental tumors. Because C. novyi-NT lyses red blood cells, we hypothesized that its membrane-disrupting properties could be exploited to enhance the release of liposome-encapsulated drugs within tumors. Here, we show that treatment of mice bearing large, established tumors with C. novyi-NT plus a single dose of liposomal doxorubicin often led to eradication of the tumors. The bacterial factor responsible for the enhanced drug release was identified as a previously unrecognized protein termed liposomase. This protein could potentially be incorporated into diverse experimental approaches for the specific delivery of chemotherapeutic agents to tumors.

Amino Acid Sequence↗
PubMed2006

The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT.

Bacteriolytic anti-cancer therapies employ attenuated bacterial strains that selectively proliferate within tumors. Clostridium novyi-NT spores represent one of the most promising of these agents, as they generate potent anti-tumor effects in experimental animals. We have determined the 2.55-Mb genomic sequence of C. novyi-NT, identifying a new type of transposition and 139 genes that do not have homologs in other bacteria. The genomic sequence was used to facilitate the detection of transcripts expressed at various stages of the life cycle of this bacterium in vitro as well as in infections of tumors in vivo. Through this analysis, we found that C. novyi-NT spores contained mRNA and that the spore transcripts were distinct from those in vegetative forms of the bacterium.

Animals↗
PubMed2006

PigGIS: Pig Genomic Informatics System.

Pig Genomic Information System (PigGIS) is a web-based depository of pig (Sus scrofa) genomic learning mainly engineered for biomedical research to locate pig genes from their human homologs and position single nucleotide polymorphisms (SNPs) in different pig populations. It utilizes a variety of sequence data, including whole genome shotgun (WGS) reads and expressed sequence tags (ESTs), and achieves a successful mapping solution to the low-coverage genome problem. With the data presently available, we have identified a total of 15 700 pig consensus sequences covering 18.5 Mb of the homologous human exons. We have also recovered 18 700 SNPs and 20 800 unique 60mer oligonucleotide probes for future pig genome analyses. PigGIS can be freely accessed via the web at http://www.piggis.org/ and http://pig.genomics.org.cn/.

Animals↗