PubMed Health⌕ Search

Biomedical subjects

Ying Zhang

Publications and source records attributed to Ying Zhang.

At least 19 recordsLinked to original sources
PubMed2026

Identification and expression validation of key genes of Xiaozhengtongluo formula in the treatment of diabetic nephropathy by Mendelian randomization.

Xiaozhengtongluo formula (XZTL) has a positive effect on the treatment of diabetic nephropathy (DN), but its mechanism is not fully understood. Therefore, it is important to explore the key genes of XZTL in the treatment of DN. Differentially expressed genes (DEGs) between DN and control obtained from GSE96804, drug target genes of XZTL, and disease target genes of DN obtained from public databases were intersected. Genes of intersection were defined as candidate genes. Next, Mendelian randomization (MR) analysis was used to ascertain the causal associations between candidate genes and DN. Afterwards, key genes were confirmed through receiver operating characteristic (ROC) curve analysis and expression validation. Subsequently, enrichment analysis, molecular regulatory network analysis, and molecular docking were conducted. Finally, experimental verification of the expression levels of key genes was performed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Altogether, 29 candidate genes were screened via MR analysis, identifying APOD, IGFBP3, and LPL as significantly associated with DN. IGFBP3 and APOD were risk factors, whereas LPL was protective. Consistent expression trends across training and validation datasets defined them as key genes. All three were co-enriched in 26 pathways, including oxidative phosphorylation. Regulatory networks showed MIR497HG/hsa-miR-19a-3p regulated IGFBP3, and NEAT1/hsa-miR-29a-3p regulated LPL; IGFBP3 and LPL were co-targeted by SP3 and SP1. Molecular docking revealed APOD-baicalein, LPL-oleic acid, and IGFBP3-quercetin binding, suggesting therapeutic potential. RT-qPCR confirmed aberrant expression of these genes in DN, which was normalized by XZTL intervention. In this study, three key genes (APOD, IGFBP3, and LPL) of XZTL in the treatment of DN were finally obtained, providing mechanistic clues for understanding XZTL's multi-target mechanism and providing experimentally tractable candidate targets for DN molecular subtyping, targeted therapeutic development, and precision medicine approaches in TCM.

Diabetic Nephropathies↗
PubMed2026

Isolation, genomic characterization, and safety assessment of an O-desmethylangolensin-producing Clostridium beijerinckii strain from Chinese Stinky Tofu.

The health benefits of dietary soy isoflavones are largely mediated by specific microbial metabolites, such as O-desmethylangolensin (O-DMA). However, the diversity and application potential of O-DMA-producing strains remain poorly explored, primarily due to the limited availability of isolated strains, narrow ecological sources, and a lack of practical applications. In this study, an O-DMA-producing bacterium, designated strain FRJF5, was isolated from Chinese stinky tofu under anaerobic conditions and was identified as Clostridium beijerinckii. The biosynthesized O-DMA exhibited an enantiomeric excess (e.e.) of 78.6%. Based on phylogenetic and average nucleotide identity analyses against 235 public C. beijerinckii genomes, the clustering of FRJF5 with strains from diverse habitats-including industrial fermentation settings, animal feces, and soil-highlights the broad ecological diversity within this species. Functional gene mining and intra-species comparative genomics revealed a unique flavonoid metabolism gene cluster in FRJF5. Using apigenin as a representative flavonoid, we confirmed the successful conversion to 3-(4-hydroxyphenyl)-propionic acid. Moreover, the strain was predicted and verified to possess a substantial butyrate-producing capacity. Genomic screening for virulence or antibiotic resistance genes, combined with phenotypic tests (hemolysis, antibiotic susceptibility, and mouse gavage), revealed a favorable safety profile for strain FRJF5. Finally, intervention experiments in a mouse model of colitis supported its potential in alleviating the disease. Collectively, this study identifies C. beijerinckii FRJF5 as a strain capable of simultaneously producing O-DMA and butyrate, highlighting its potential for future applications in functional foods.IMPORTANCESoy isoflavones require gut bacterial conversion into bioactive metabolites-such as the anti-inflammatory compound O-desmethylangolensin (O-DMA)-to exert health benefits. Yet O-DMA-producing strains remain scarce, largely confined to fecal sources, and poorly characterized. Here, we isolated Clostridium beijerinckii FRJF5 from Chinese stinky tofu, an unexplored ecological niche. This strain not only produces enantiomerically enriched O-DMA but also co-produces butyrate, a metabolite known to strengthen gut barrier function. Genomic mining uncovered a unique flavonoid metabolism gene cluster responsible for this dual activity. Combined with favorable safety profiles, FRJF5 emerges as a strong candidate for functional food applications. This work expands the known diversity of O-DMA producers and bridges traditional fermented foods with next-generation probiotic development.

O-desmethylangolensin↗
PubMed2026

Identification and Catalytic Optimization of Pinene Oxidases in Paeoniflorin Biosynthetic Pathway.

Paeoniflorin is a pharmacologically important cage-like monoterpene glycoside characteristic of Paeonia plants, yet its biosynthetic pathway has remained largely unresolved, hindering sustainable production. Here, we confirmed that paeoniflorin biosynthesis originates from α-pinene and identified three novel cytochrome P450 enzymes that catalyze pinene oxidation. CYP71AN126 catalyzes the hydroxylation of α-pinene at positions C4 and C10, followed by further oxidation of the alcohol to a ketone at C4, whereas CYP76A225/226 exclusively catalyze C10 hydroxylation. Virus-induced gene silencing (VIGS) assays demonstrated that silencing CYP71AN126, but not CYP76A225 and CYP76A226, significantly reduced the paeoniflorin content, indicating that C4 hydroxylation plays an important role in paeoniflorin biosynthesis, whereas C10 hydroxylation is not. Through the analysis of natural sequence and activity divergence among CYP71AN126 and CYP76A225/226, combined with protein structure prediction and site-directed mutagenesis, we identified L493 as a critical residue involved in regulating catalytic site specificity and substrate specificity of CYP71AN126. Mutation of L493 reduced or eliminated the formation of undesired C10 hydroxylation side-product and enhanced substrate specificity. These findings establish C4 oxidation of α-pinene as the critical committed step in paeoniflorin biosynthesis. Our study lays a foundation for elucidating the complete biosynthetic pathway of paeoniflorin in Paeonia and provides a target for enzyme engineering of CYP71AN126 aimed at the efficient production of paeoniflorin via synthetic biology approaches.

Paeonia genus↗
PubMed2026

Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems.

Prime editing holds promise for therapeutic applications. However, viral delivery of the prime editor presents challenges for clinical translation due to concerns regarding long-term expression. Meanwhile, systemic delivery using non-viral vectors has been limited by low efficiency, the need for repeated injections and reliance on doses that exceed clinically translatable levels. Here we develop engineered prime editing guide RNAs (pegRNAs) with densely modified RNA motifs and demonstrate their application for efficient in vivo prime editing. By systemically delivering the prime editor in RNA format via a single injection of lipid nanoparticles, we achieved nearly 70% editing efficiency in the bulk mouse liver, indicating successful editing of the majority of hepatocytes. Notably, a single injection at a clinically translatable lipid nanoparticle dose was sufficient to suppress target protein expression in vivo, resulting in a near 80-fold increase in editing efficiency compared with conventional end-modified pegRNAs. Furthermore, incorporating densely modified RNA motifs, including the widely used MS2 motif, proved broadly applicable across various RNA sequences and split RNA-guided genome editing platforms, resulting in up to an 11-fold increase in base editing efficiency. These findings present a generalizable approach for enhancing the therapeutic potential of prime editing and expanding the utility of RNA-based therapeutics.

Journal Article↗
PubMed2026

Genetic and pathogenic characterization of a novel infectious bursal disease virus field strain with natural reassortant and recombinant features from southern China.

NN040124 is a novel field-derived IBDV strain (vv-A/att-B) exhibiting both reassortment and recombination events.Infection with NN040124 causes 40% mortality and severe lymphoid depletion in three-yellow chickens.These findings demonstrate the pivotal role of the N-terminal domain of segment B in IBDV pathogenicity and virulence.

A3B1a↗
PubMed2026

Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans↗
PubMed2026

Driver genomic lesions in MDM2, CDK4, and JUN co-opt targetable super-enhancer networks to impose liposarcomagenic core regulatory circuitry.

INTRODUCTION: Amplification of chromosome 12q13-15 spanning MDM2 and CDK4 genes serves as a molecular diagnostic hallmark of dedifferentiated liposarcoma (DDLPS), an aggressive soft-tissue sarcoma. Epigenetic activation of master transcription factors (RUNX proteins, FOSL2, and MYC) establishes a self-reinforcing oncogenic transcriptional circuitry in DDLPS. Nevertheless, the collaborative interplay between genomic alterations and epigenetic dysregulation in defining DDLPS cell identity remains elusive. OBJECTIVES: This work aimed to elucidate the primary genetic drivers and mechanistic basis of DDLPS-specific core transcriptional regulatory circuitry. METHODS: We performed integrative chromatin profiling analysis of DDLPS clinical specimens and cell lines to map cis-regulatory landscapes. Cistromes of MDM2, JUN, and E2F1 were delineated through chromatin immunoprecipitation sequencing in two DDLPS models. Essential driver functions and transcriptional regulatory effects of key regulators were assessed via various genetic manipulation approaches. Synergistic interactions between BET-targeting agents and MDM2/p53 or CDK4 inhibitors were quantified by cell viability assays. In vivo xenograft assays evaluated the oncogenic potential of key regulators and the therapeutic efficacy of novel strategies. RESULTS: Co-amplification of MDM2, CDK4, and JUN during sarcomagenesis converges with BET protein-dependent chromatin remodeling to fuel feed-forward transcriptional circuits among master transcription factors. Mechanistically, excessively expressed MDM2 stabilizes the core regulatory circuitry by forming chromatin-bound complexes with JUN/FOSL2 at cis-regulatory elements, especially super-enhancers across DDLPS genome. Concurrently, CDK4 maintains expression of E2F1 which further fosters transcriptional output of master transcription factors in DDLPS cells. Leveraging DDLPS-selective overexpression of MDM2 and its E3 ligase activity, targeted degradation of BET proteins by MDM2-recruiting proteolysis targeting chimera selectively disrupted the core regulatory circuitry, suppressing DDLPS growth and exhibiting strong synergy with CDK4 inhibitor. CONCLUSION: DDLPS-associated genomic lesions collaborate with BET-dependent chromatin regulation to establish disease-sustaining transcriptional circuitry. Our findings also provide a mechanistic rationale for harnessing MDM2's E3 ligase activity to therapeutically degrade oncoproteins in MDM2-amplified malignancies.

Core transcriptional regulatory circuitry↗
PubMed2026

Haplotype-resolved 3D genome maps reveal RNAPII-mediated allelic regulation in hybrid rice.

To understand how the two parental genomes coordinate transcription in hybrids, chromatin architecture must be resolved at the haplotype level. Here, using phased Bridge-Linker Hi-C, we reconstructed a haplotype-resolved three-dimensional (3D) genome of the elite hybrid rice (Oryza sativa) line Shanyou 63 (SY63). We identified extensive allele-specific chromatin conformations. Furthermore, we generated allele-resolved RNAPII ChIA-PET maps and phased transcriptomes to explore how chromatin interactions contribute to allelic regulation. Although maternal and paternal homologs share broadly similar chromatin features, we detected widespread haplotype-biased RNAPII binding and chromatin looping at high resolution. These allele-specific RNAPII-mediated contacts were significantly associated with biased expression. Stronger RNAPII binding on one haplotype promoted the formation of long-range regulatory loops with distal genes, thereby contributing to allele-biased transcription at a subset of loci, even when promoter-proximal RNAPII occupancy was comparable between alleles. These results demonstrate that subtle differences in RNAPII engagement and 3D regulatory wiring between parental haplotypes can reshape transcriptional output in hybrids, providing new insights into the mechanisms underlying the allelic regulation of gene expression.

Allele-specific chromatin interactions↗
PubMed2026

Integrative WGBS and ATAC-seq profiling reveals epigenetic and chromatin accessibility signatures associated with clutch length in goose ovaries.

Clutch length is an important reproductive trait in geese, but its epigenetic basis remains poorly characterized. Daily egg production was recorded for 280 individually housed Zi geese, and clutch-related indices were calculated as described in our previous study. Based on these records, six geese with contrasting clutch-length phenotypes were selected and assigned to the long-clutch (LC) and short-clutch (SC) groups. Ovarian tissues from three geese per group were subjected to whole-genome bisulfite sequencing (WGBS) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) to identify candidate epigenetic signatures associated with clutch length. WGBS identified 630,909 differentially methylated regions (DMRs), whereas ATAC-seq identified 902 differentially accessible regions (DARs). Integrated analysis revealed distinct patterns of ovarian DNA methylation and chromatin accessibility between the two groups, suggesting that clutch length variation may be accompanied by epigenomic differences in ovarian tissue. Genes associated with DMRs and/or DARs were enriched in biological processes related to granulosa cell differentiation and endocrine competence, follicular fate regulation, and periovulatory cytoskeletal and signaling remodeling. RERE was prioritized as a candidate locus because it was supported by changes in both DNA methylation and chromatin accessibility, whereas FOXL2, STAR, BAK1, FGF17, PRSS35, ACTR3, and AXIN1 were supported mainly by evidence from a single omics layer. RT-qPCR analysis of selected genes showed expression trends broadly consistent with the corresponding epigenomic differences, providing additional supportive evidence for these candidate associations. Collectively, this study provides an exploratory ovarian epigenomic resource and identifies candidate epigenetic signatures, genes, and biological processes associated with clutch length variation in geese.

DNA methylation↗
PubMed2026

Early proteomic and metabolic signatures of liver and eye in OAT-deficient mice.

Ornithine aminotransferase (OAT) deficiency causes hyperornithinemia and gyrate atrophy (GA) of the choroid and retina, a rare inherited retinal degeneration. To understand the early molecular changes that make the eye susceptible to damage, we performed quantitative proteomic and metabolomic profiling of liver, retina, and retinal pigment epithelium and choroid (RPE/Cho) from OAT-deficient (Oatrhg) mice prior to detectable vision impairment. In addition to reduced OAT expression and elevated ornithine, methylation-related metabolites such as N(6)-methyl-lysine were altered in all examined tissues of Oatrhg mice. In the liver, excess ornithine was directed into urea cycle metabolism, together with altered expression of detoxification enzymes and histone H2B proteins. In contrast, the retina showed minimal proteomic changes but pronounced alterations in amino acid pathways that support glutamate homeostasis. The RPE/Cho demonstrated the most extensive proteomic changes, particularly in mitochondrial metabolism, cytoskeleton, and extracellular matrix, along with changes in metabolites involved in lysine metabolism, energy metabolism, and antioxidant capacity. Incubation with 13C lysine demonstrated that lysine was primarily degraded in RPE/Cho but not the retina, and ornithine enhanced lysine degradation in an OAT-dependent manner. Together, these findings highlight common and tissue-specific impacts of OAT on the liver and ocular tissues and provide insight into early molecular changes that contribute to the selective vulnerability of the eye in GA. Proteomics data are available via ProteomeXchange (PXD063614) and metabolomics data via MassIVE repository (MSV000101103).

Animals↗
PubMed2026

Combined effects of urine exposure and cryopreservation on sperm quality: an in vitro study of retrograde ejaculation.

Sperm quality influences fertility and offspring health through both genomic inheritance and epigenetic inheritance. Thus, for use in clinical-assisted reproductive technology (ART), spermatozoa must have optimal genomic and epigenetic structures. In patients with retrograde ejaculation, spermatozoa are usually recovered from urine and then cryopreserved for ART. However, the effects of urine exposure and subsequent freeze-thaw cycles on sperm quality remain unclear. This is particularly true for epigenetic changes and their underlying mechanisms. In this study, we examined how different durations of urine exposure (10 min and 40 min) followed by freeze-thaw cycles affected sperm motility, DNA integrity, and methylation levels of imprinting genes (H19-imprinted maternally expressed transcript [ H19 ], mesoderm-specific transcript [ MEST ], and the transposable element Alu [ Alu ]). As the duration of urine exposure increased, sperm motility (median [interquartile range]) decreased from 48.0% (39.0%-52.5%) to 1.0% (1.0%-5.0%), the DNA fragmentation index (DFI; median [interquartile range]) increased from 12.0% (9.3%-19.9%) to 23.5% (13.9%-33.9%), the MEST methylation level (mean &#xb1; standard deviation [s.d.]) increased from 3.8% &#xb1; 1.5% to 11.5 &#xb1; 1.2%, and the H19 methylation level (mean &#xb1; s.d.) decreased from 86.9% &#xb1; 0.9% to 82.1% &#xb1; 0.5%. The freeze-thaw process further reduced sperm motility, while the DFI and methylation levels of MEST and H19 did not significantly change. The Alu methylation level remained stable. These findings demonstrate that urine exposure affects sperm motility, DNA integrity, and methylation levels of some imprinting genes. These effects intensify over time. In contrast, the freeze-thaw process impacts only sperm motility. In clinical practice, minimizing exposure to urine might improve sperm quality.

Humans↗
PubMed2026

A genetic manipulation tool based on the GP35 recombinase for targeted gene editing in mycoplasmas of ruminants.

Pathogenic ruminant mycoplasmas are major etiological agents in cattle and small ruminants and are responsible for substantial economic losses in the livestock industry. Progress in pathogenesis research and vaccine development has been hampered by a lack of effective genetic tools. The applicability of common genome editing platforms, such as CRISPR, is inherently restricted in these organisms owing to their minimal genomes, the absence of a cell wall, and low homologous recombination efficiency. Although transposon-mediated random mutagenesis and single-base editing are currently used in the editing of bovine mycoplasma, the stochastic nature of transposons, the risk of single-base random deamination, and limitations in editing window selection hinder the genetic manipulation of bovine mycoplasma. Here, we introduce a plasmid-based methodology that employs the GP35 recombinase from bacteriophage SPP1 to mediate long single-stranded DNA (ssDNA) recombineering, thereby enabling precise gene insertions and deletions in Mycoplasma bovis, with a positive-editing rate of 77.78% - 100%. This targeted system eliminates the risk of random deamination. Leveraging this tool, we generated a panel of M. bovis mutants affecting metabolic and virulence genes and obtained key insights into Mb0564, identified as a novel adhesin. The 192 to 287 aa region of GP35 is critical for interaction with SSB. Structural conservation analysis further suggested that this GP35-ssDNA editing system possesses a high potential for translation to other ruminant pathogens. Collectively, our approach expands the existing genetic toolkit for M. bovis, advances synthetic biology and M. bovis pathobiology, facilitates vaccine development, and strengthens the control of high-impact livestock diseases in line with the One Health framework.

Animals↗
PubMed2026

Effects of Family-Based Intervention for Childhood Obesity on Parental and Offspring Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Childhood obesity is a global public health issue with strong familial and intergenerational transmission. However, existing syntheses often overlook the active role of parents and fail to assess outcomes beyond the child. This systematic review and meta-analysis specifically investigate the effects of family-based interventions, which position parents as active co-agents of change, on health outcomes for both children with obesity and their parents. METHODS: A systematic review and meta-analysis were conducted. Six databases were searched for randomized controlled trials (RCTs) targeting children with obesity and at least one family member. Primary outcomes were children's BMI z-score and parental BMI; secondary outcomes included other adiposity measures and dietary behaviors. Outcomes for both children and parents were synthesized. Subgroup analyses were conducted based on intervention characteristics. Risk of bias was assessed using RoB 2, and evidence certainty was evaluated using GRADE. RESULTS: Twenty RCTs with 1740 participants were included in the meta-analysis. The interventions demonstrated a significant reduction in children's BMI z-score. Additional benefits were observed for long-term BMI z-score and percentage of total body fat. The most effective interventions commonly integrate health education, behavioral strategies, and motivational support. Subgroup analyses indicated that interventions positioning parents as active co-participants, rather than mere supporters, yielded larger effects. However, no significant effects were found on parental BMI. CONCLUSION: This study demonstrates that family-based interventions can confer significant benefits for children with obesity. Their success hinges on strategically framing parents as active co-agents and integrating motivational strategies.

Humans↗
PubMed2026

Health bill beneath the plastic feast: A phthalate contamination alert from takeout food containers.

The rapid growth of takeout food consumption in China has raised concerns regarding exposure to phthalic acid esters (PAEs) from food packaging. This study investigated the presence, source, contribution, and health risk of PAEs in commonly used takeout containers. Widespread contamination was observed, with total PAE concentrations ranging from below the limit of detection to 222,000 ng/g. Diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified as the predominant compounds, accounting for 7.50 %, 14.7 %, and 18.7 % of the total concentration, respectively. These PAEs may originated from additives during manufacturing and potential contamination of raw materials. Human exposure assessment showed that daily exposure doses of DIBP, DBP, and DEHP via container ranged from 0.00 to 2340 ng/(kg&#xb7;day) among frequent takeout consumers, contributing substantially to overall PAE body burdens. To further assess exposure and associated risks, a nationwide online questionnaire survey was conducted across China. Based on this national-scale behavioral dataset, the health risks among Chinese residents were evaluated. Although the modeled non-carcinogenic risks of DIBP, DBP, and DEHP remained within acceptable limits, the simulation suggested that approximately 70 % of participants may experience potential exceedance of the carcinogenic risk threshold for DEHP. The frequency of takeout food consumption was identified as the most important factor affecting PAE exposure. These findings underscore the importance of limiting takeout frequency and reducing reliance on plastic containers to mitigate health risks. This study provides scientific evidence to support the development of safer packaging materials and informs public health strategies.

Phthalic Acids↗
PubMed2025

ANXA3 hypomethylation as a prognostic biomarker in hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a poor prognosis. This research aimed to characterize the expression pattern and clinical value of Annexin A3 (ANXA3) in HBV-ACLF patients. METHODS: First of all, ACLF-related datasets were downloaded from the Gene Expression Omnibus (GEO) database to carry out bioinformatics analyses. RT-qPCR, ELISA, and Methylight were used to measure ANXA3 gene expression and promoter methylation levels. A validation cohort was leveraged to further validate the results. RESULTS: Transcriptome analysis showed that ANXA3 was among the most differentially expressed genes when comparing dead patients with HBV-ACLF to those with survivors. The mRNA and serum levels of ANXA3 were elevated, and methylation levels were decreased in HBV-ACLF patients. The PMR value of ANXA3 in patients with HBV-ACLF was negatively correlated with inflammation-related cytokines IL-6, TNF-&#x3b1;, and IL-1&#x3b2;, as well as quantitative clinical parameters AST, TBIL, PT, INR, NEUT%, and MELD score, and positively correlated with PTA (all p&#x2009;<&#x2009;0.05). In HBV-ACLF patients, ANXA3 was considered to be an independent influence factor for the 90-day mortality. It was also found that ANXA3, especially hypomethylation, was associated with 28- and 90-day overall survival in patients with HBV-ACLF based on receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and Kaplan-Meier curves. CONCLUSIONS: ANXA3 hypomethylation has a prominent predictive value for short-term mortality in patients with HBV-ACLF and may serve as a promising biomarker of HBV-ACLF prognosis.

Humans↗
PubMed2025

Novel mutations associated with clofazimine resistance in Mycobacterium intracellulare.

BACKGROUND: Clofazimine is a promising repurposed drug for treating Mycobacterium avium-intracellulare complex pulmonary disease, but its resistance mechanisms in Mycobacterium intracellulare remain poorly understood. OBJECTIVE: This study aims to elucidate the resistance mechanisms of M. intracellulare to clofazimine. METHODS: We isolated 36 clofazimine-resistant M. intracellulare mutants in vitro and performed whole-genome sequencing to identify resistance-associated mutations. Gene complementation was used to validate the role of the identified mutations. RESULTS: We identified various mutations in the marR gene (WP_009952290.1) in 61% of clofazimine-resistant mutants by whole-genome sequencing. Mutations were identified in additional genes encoding ssuD (flavin-dependent oxidoreductase, C67A), lppI (membrane lipoprotein, C207 deletion), GMC oxidoreductase (glucose-methanol-choline oxidoreductase, G157 deletion), MASE1 domain-containing protein (C62G) and PPE family protein (222C deletion). Gene complementation experiments demonstrated that introducing the wild-type marR in clofazimine-resistant strain (L72) with marR mutations reduced clofazimine MIC from 1 mg/L to susceptible baseline (0.25 mg/L), confirming its critical role in clofazimine resistance. Notably, the M. intracellulare MarR lacks homology to Mycobacterium tuberculosis MarR family protein Rv0678 (MmpR) involved in clofazimine and bedaquiline resistance but is flanked by non-efflux pump genes (dhmA and doxX), and unlike M. tuberculosis, its mutation does not cause bedaquiline cross-resistance, indicating a different MarR and distinct regulatory mechanism for clofazimine resistance in M. intracellulare. CONCLUSIONS: This work highlights marR as a key determinant of clofazimine resistance in M. intracellulare and underscores the need for further mechanistic studies with implications for rapid molecular detection and effective treatment.

Clofazimine↗
PubMed2025

eccDNABase: A Comprehensive and High-Quality Database for Extrachromosomal Circular DNA.

Extrachromosomal circular DNA (eccDNA) refers to small, circular DNA molecules that originate from chromosomal sequences and are prevalent across nearly all eukaryotic organisms. In humans, eccDNAs are widely distributed in normal tissues, cancerous tissues, and body fluids, where they play important roles in tumorigenesis and are often associated with poor clinical outcomes. Given their biological and clinical significance, a well-integrated and high-quality database is essential for advancing eccDNA-related research. To address this need, we developed eccDNABase, a comprehensive and curated resource for browsing, searching, and analyzing eccDNAs across multiple species. The database systematically catalogs eccDNA-disease associations from diverse tissues and organisms. Currently, eccDNABase contains 1,875,452 eccDNA-disease associations, encompassing 8,398 ecDNA entries across nine species, 63 diseases, and healthy individuals. Each entry provides detailed information, including eccDNA ID, type, chromosomal localization, species, tissue or cell line source, disease name and Disease Ontology ID, overlap length and percentage with genes, oncogene overlap, detection method, and links to literature and source databases. Given its extensive and curated datasets, eccDNABase serves as a valuable resource for both basic and translational research, offering deeper insights into the role of eccDNA in health and disease. The database is publicly accessible at http://cgga.org.cn/eccDNABase/.

Humans↗