Biomedical subjects

Ying Huang

Publications and source records attributed to Ying Huang.

11 recordsLinked to original sources

PubMed2026

Gdt1, Gdt2 and the P-type ATPase Pmr1 regulate divalent cations (Ca²⁺ and Mn²⁺) in the fission yeast Schizosaccharomyces pombe.

In eukaryotes, calcium (Ca²⁺) and manganese (Mn²⁺) ion homeostasis in the early secretory pathway is crucial for protein glycosylation, cell wall biosynthesis, and cell structure. To clarify the roles of the UPF0016 family proteins Gdt1 and Gdt2 in the regulation of divalent cations, we performed genetic and phenotypic analyses on single-gene deletion mutants (Δgdt1, Δgdt2 and Δpmr1) and double-gene deletion mutants in Schizosaccharomyces pombe. In the presence of CaCl₂ and MnCl₂, Δgdt1 cells exhibit marked hypersensitivity, indicating that Gdt1 is a major contributor to divalent cation regulation; in contrast, Δgdt2 and Δpmr1 mutants show only mild growth defects. However, the combined deletion of gdt1 or gdt2 with pmr1 results in a strong synthetic growth phenotype, suggesting that Gdt1, Gdt2, and Pmr1 play complementary roles in maintaining divalent cation regulation within the secretory network. Structural comparative analysis reveals that Gdt1 retains a conserved five-transmembrane structure, whereas Gdt2 adopts a six-transmembrane conformation. Both proteins preserve the EIGDKT and EWGDRS motifs characteristic of UPF0016 transporters. These findings establish Gdt1 as a key determinant of Ca²⁺ and Mn²⁺ regulation and support a complementary role for Gdt2 in ion regulation, a process essential for efficient glycosylation and normal cell wall morphogenesis.

Schizosaccharomyces pombe↗

PubMed2026

Directed evolution of Lactiplantibacillus plantarum for utilizing ethanol to produce postbiotics.

Alcohol is a recognized carcinogen worldwide. In this study, we aimed to utilize probiotics to metabolize ethanol and produce postbiotics. Initially, we identified a lactic acid bacteria community in kimchi with excellent probiotic activity. By employing our previously developed directed evolution techniques, a Lactiplantibacillus plantarum mutant with safe characteristics and an ethanol utilization capacity of 40 g/L and 0.15 g/L/OD was obtained. Genome sequencing and RT-qPCR analysis revealed the up-regulated expression of alcohol dehydrogenase and aldehyde dehydrogenase genes greatly contributed to ethanol utilization. Furthermore, the mutant strain demonstrated marked superiority in producing postbiotics, including antimicrobial peptides and beneficial organic acids such as lactic acid, phenyllactic acid, succinic acid, and indole-3-lactic acid. In the ethanol-fed fermentation process, the mutant strain achieved a lactic acid yield of 8.47 g/L and a carbon conversion rate of 21.8%. In vivo testing further validated its safety and ability to assist alcohol metabolism.

Adaptive laboratory evolution↗

PubMed2026

A therapeutic atlas of monogenic inflammatory bowel disease.

BACKGROUND AND AIMS: Evidence-based, mechanism-guided therapies are urgently needed for treating monogenic inflammatory bowel disease (mIBD). For such rare diseases, mechanistic insight is essential to guide treatment when conventional clinical trials are often not feasible. We aimed to summarize literature-based evidence and to identify knowledge gaps. METHODS: We conducted a systematic review of published manuscripts evaluating the therapeutic efficacy in mIBD. We quantified and compared the global therapeutic response score across treatments and conditions. In a subset of conditions, biomarkers of longitudinal therapeutic response were evaluated in comparison to non-monogenic pediatric IBD cohorts. RESULTS: Responses to 35 therapeutics across the 102 known genetic causes of mIBD were evaluated in 241 articles and 669 patients, summarizing 302 gene-drug responses. The efficacy of at least one pharmacological intervention was identified in 61% (n = 62/102) of the mIBD conditions, highlighting a major unmet need for effective medications in many others. Gene- and pathway-specific responses were demonstrated for several therapies, including allogeneic hematopoietic stem cell transplantation, gene therapy, and advanced therapies such as anti-TNF agents, IL-1 inhibitors, mTOR inhibitors, as well as eculizumab in CD55 deficiency, abatacept in CTLA4 deficiency, and the immunometabolic agent empagliflozin in glycogen storage disease type 1b. CONCLUSIONS: This study highlights the potential of precision medicine approaches tailored to genetic and pathway-specific mechanisms, while underscoring the urgent need for effective therapies in many monogenic conditions that remain without established treatment options.

Humans↗

PubMed2026

Pan-Genomic Dissection of GH1 β-Glucosidases in Brassica rapa Identifies BrBGLU10 as an Important Regulator of Pollen Development.

Glycoside hydrolase family 1 (GH1) β-glucosidases (BGLUs) play diverse roles in plant development and stress responses. However, a comprehensive pan-genomic characterization of this gene family across diverse Brassica rapa accessions is still lacking. Here, we conducted a pan-genome-wide analysis of BGLU genes across 21 B. rapa accessions. A total of 1840 BGLU genes were identified and clustered into 57 orthologous gene groups (OGGs), comprising 22 core, 19 dispensable, and 16 private groups. Phylogenetic reconstruction assigned these OGGs to five subgroups, and duplication analysis revealed whole-genome duplication as the predominant driver of family expansion, accounting for 47.51% of duplicated genes. Expression profiling identified two core genes, BrBGLU10 and BrBGLU56, as specifically expressed in fertile floral buds and differentially regulated between fertile and sterile lines. CRISPR/Cas9-mediated knockout of BrBGLU10 resulted in approximately 36% pollen abortion and drastically reduced seed set upon self-pollination, supporting its important role in pollen development. Collectively, these findings establish BrBGLU10 as an important regulator of pollen development and a potential target for fertility-related applications via gene editing in B. rapa and related Brassica crops.

BrBGLU10↗

PubMed2026

Insights into phylogenetic relationships of Veronica species (Plantaginaceae) based on comparative chloroplast genomics.

INTRODUCTION: Veronica L. is one of the most species-rich genera in Plantaginaceae and several species have medicinal, horticultural, or ecological value. METHODS: In this study, the complete chloroplast genomes of three Veronica species were assembled and annotated using Illumina sequencing data. RESULTS: The plastomes exhibited a typical quadripartite structures, with total lengths of 150,202 bp for Veronica biloba L., 151,159 bp for Veronica ciliata Fisch. and 151,098 bp for Veronica vandellioides Maxim. Each genome contained 130-132 unique genes, including 86-87 protein-coding genes, 36-37 tRNA genes, and 8 rRNA genes. Comparative analyses of 24 Veronica plastomes indicated that the IR/SC junctions were largely conserved, although slight boundary shifts occurred around rps19, ndhF, and ycf1. Forward, palindromic, complement, and reverse repeats were detected, and A/T mononucleotide repeats were the dominant SSR type. Nucleotide diversity analysis identified rpl32-trnL, trnK-rps16, rpl32, ycf1, ndhF, accD, matK, and rpoB as highly variable regions. Phylogenetic analyses recovered Veronica as a well-supported monophyletic lineage and clarified the plastid positions of the three newly sequenced species. Divergence time estimation suggested that the estimation suggested of Veronica was around 14.9 Ma, with V. biloba, V. ciliata and V. vandellioides diverging approximately 3.9 Ma, 0.6 Ma, and 6.9 Ma, respectively. DISCUSSION: Because the analyses were based on plastid genomes, the inferred topology should be interpreted as chloroplast phylogenetic evidence rather than a complete species-history reconstruction. These results provide plastome resources and molecular evidence for taxonomy, species identification, and future evolutionary studies of Veronica.

Plantaginaceae↗

PubMed2026

Integrative multi-omics and machine learning identify the SPI1-METTL16-PLIN4 axis as a candidate driver of steatosis in HepG2 cells.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with limited therapeutic options. This study aimed to identify potential regulators and explore their functional roles in a cellular model of NAFLD. METHODS: WGCNA was performed on the hepatic transcriptomic dataset GSE126848 (31 NAFLD vs. 26 controls), followed by integration with serum proteomic data from 12 NAFLD patients and 12 healthy controls. Hub genes were prioritized using three machine learning algorithms. Functional validation was conducted in a HepG2 cellular steatosis model induced by high fructose (3.2 g/L) and oleic acid (400 μM) for 48 h. Lipid accumulation was assessed by Oil Red O staining and triglyceride/total cholesterol measurement. Inflammation was evaluated by TNF-α and IL-6 secretion (ELISA), and oxidative stress by ROS levels (flow cytometry). The binding interaction between METTL16 and PLIN4 mRNA was validated by RNA immunoprecipitation (RIP)-quantitative PCR. METTL16-mediated m6A modification of PLIN4 was assessed by Methylated RIP (MeRIP)-quantitative PCR. Transcriptional regulation of METTL16 by SPI1 was examined by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: Integrative analysis identified PLIN4 as a core hub gene. PLIN4 was upregulated in the HepG2 steatosis model (P < 0.001). PLIN4 knockdown alleviated lipid droplet accumulation (P < 0.001), reduced TNF-α and IL-6 secretion (P < 0.01), and decreased ROS levels (P < 0.001) in fructose/oleic acid-treated HepG2 cells. Mechanistically, METTL16 mediated its m6A modification to enhance PLIN4 mRNA stability. Furthermore, SPI1 was found to transcriptionally activate METTL16 by binding to its promoter (P < 0.001). PLIN4 re-expression partially reversed the protective effects of SPI1 knockdown on lipid accumulation (P = 0.01), inflammation (P < 0.05), and oxidative stress (P < 0.001). CONCLUSION: This study identifies the SPI1/METTL16/PLIN4 axis as a potential regulatory mechanism contributing to in vitro steatosis, inflammation, and oxidative stress in steatotic HepG2 cells.

Humans↗

PubMed2026

ZNF695 Promotes Colorectal Cancer Progression Through Transcriptional Activation of CBX8 and Subsequent Wnt/β-Catenin Signaling Activation.

In this investigation, we examined the functional mechanism of the transcription factor zinc finger protein 695 (ZNF695) and its target gene chromobox protein homolog 8 (CBX8) in colorectal cancer (CRC) migration and invasion. HCT-116 and LOVO cell lines were used to establish cell models with knocked-down ZNF695 and knocked-down or over-expressed CBX8. To comprehensively evaluate the functional contributions of ZNF695 and CBX8 to cellular phenotypes, we employed CCK-8, wound-healing, and Transwell assays to evaluate cell proliferation, migration, and invasion, respectively. To assess the impact of ZNF695 on tumor progression, we generated a xenograft model utilizing nude mice. A FLAG-ZNF695 expression plasmid was constructed, and ChIP-seq experiments were performed. By integrating mRNA sequencing data following ZNF695 knockdown with highly expressed genes in CRC from the TCGA database, CBX8 was identified as a putative downstream target of ZNF695. We employed a dual-luciferase reporter assay to validate the specific binding affinity of ZNF695 toward the CBX8 promoter region. To elucidate the specific biological cascades modulated by ZNF695 and CBX8, we conducted a comprehensive pathway enrichment analysis. Rescue experiments were conducted to determine whether the ZNF695/CBX8 regulatory axis upregulates the expression of the Wnt signaling pathway downstream targets, AXIN2 and CCND1. Both in vitro assays and in vivo models confirmed that silencing ZNF695 dramatically suppresses CRC cell proliferation, migration, and invasion, while concurrently impeding tumor progression. ChIP-seq coupled with dual-luciferase reporter assays substantiated the direct binding of ZNF695 to the CBX8 promoter. Furthermore, CBX8 depletion significantly attenuated the migratory and invasive phenotypes of CRC cells. Restoring CBX8 expression effectively rescued the migratory and invasive deficits in CRC cells induced by ZNF695 silencing. Re-expression of CBX8 in ZNF695-silenced cells restored Wnt/β-catenin signaling activity, accompanied by increased expression of AXIN2 and CCND1. ZNF695 promotes CRC progression by transcriptionally activating CBX8 and subsequently enhancing Wnt/β-catenin signaling, thereby promoting tumor cell proliferation, migration, and invasion.

Humans↗

PubMed2026

Prospective clinical validation of targeted long-read sequencing for preimplantation genetic testing of α-thalassaemia.

BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) can prevent transmission of severe α-thalassaemia, but conventional workflows remain limited by family-specific assay design for direct variant detection, dependence on additional family samples for haplotype construction, and labour-intensive multi-step procedures across several platforms. Targeted long-read sequencing-based PGT-M for α-thalassaemia (tlrPGT-α-thal) integrates direct variant detection and haplotype linkage analysis within a single assay, but prospective clinical validation is lacking. METHODS: This prospective clinical study enrolled 103 families at high risk of transmitting α-thalassaemia at a reproductive medicine centre between August 2024 and March 2025. All families underwent blinded parallel analysis using both conventional NGS-based PGT-M (comparator) and tlrPGT-α-thal. RESULTS: In the primary concordance analysis, tlrPGT-α-thal was fully concordant with conventional NGS-based PGT-M (507/507, 100.0%; exact 95% CI, 99.3-100.0). Direct variant detection was successful in 501/507 embryos (98.82%; 95% CI, 97.4-99.6), haplotype linkage was established in 505/507 embryos (99.61%; 95% CI, 98.6-100.0), and one meiotic recombination event was identified. Among 93 families proceeding to embryo transfer, 57 pregnancies underwent invasive prenatal diagnosis, and all were concordant with the corresponding tlrPGT-α-thal results. Of the 26 comparator-inconclusive embryos, tlrPGT-α-thal resolved 6 complex cases, including cases with incomplete pedigrees or insufficient informative SNPs. Among the remaining 20 embryos with HBA-region aneuploidies, genotype and parental origin could be determined in 12. CONCLUSIONS: The findings show that tlrPGT-α-thal enables direct detection of diverse α-thalassaemia-causing variants together with efficient haplotype linkage analysis within a single workflow, without requiring family-specific assay design or additional family samples. The method demonstrated high diagnostic accuracy while providing added value in complex scenarios. Taken together, tlrPGT-α-thal represents a simplified and broadly applicable strategy for α-thalassaemia PGT-M.

Humans↗

PubMed2026

Mitochondrial dysfunction in the pathogenesis of intervertebral disc herniation: a mitochondrial related genome-wide Mendelian randomization analysis.

BACKGROUND: As a degenerative disease, the pathophysiology of intervertebral disc herniation (IDH) closely related to mitochondrial dysfunction. However, the specific molecular mechanisms involved have yet to be precisely established. METHODS: Here, we employed a two-sample, two-step Mendelian Randomization (MR) approach, along with summary-Data-Based MR, genetic colocalization, full phenomenon association analysis, and GO and KEGG enrichment analysis to investigate the genetical effects of mitochondrial dysfunction on IDH. RESULTS: From the intercross between mitochondrial-related genes and eQTLGen genes, we obtained seven genes (DMPK, EHHADH, SLC25A16, ME3, METTL17, TUFM, NDUFA13) with strong causal association with disc herniation. By SMR and genetic colocalization analysis, we further identify five key genes (EHHADH, METTL17, TUFM, NDUFA13, DMPK) as the direct causal tartgeted genes with no heterogeneity and pleiotropy in the SNPs of the genes. Full phenomenon Mendelian randomization was performed to determine possible side effects of the 5 targeting genes. Finally, we validated the expressions of key genes in the degenerative intervertebral discs tissues by qRT-PCR and double-immunofluorescence examinations, and the results were consistent with the MR analysis. CONCLUSIONS: Our study provided genetic support for the relationship between mitochondrial related genes and IDH, implicating potential therapeutic targets for future development. However, more basic experiments need to be finished to validate the role of key genes in the development of IDH.

Intervertebral Disc Displacement↗

PubMed2026

Eco-evolutionary dynamics sustain a potent yet rare antibiotic gene cluster in Streptomyces.

Microbial secondary metabolites have been recognized and utilized for nearly a century. Nevertheless, the eco-evolutionary mechanisms governing their distribution among microorganisms remain largely unresolved. In this study, we examined intraspecific interactions within Streptomyces albidoflavus and identified a strain exhibiting potent antagonistic activity against conspecifics. This "killer" phenotype was attributed to the production of kosinostatin, a hybrid aromatic polyketide antibiotic. Evolutionary genomic analyses provided strong evidence that the kosinostatin biosynthetic gene cluster was horizontally acquired in S. albidoflavus over a relatively short evolutionary timescale, a finding consistent with its sparse distribution within this species, across the genus Streptomyces, and even throughout the phylum Actinomycetota. Using microcosm assays, we demonstrated that the kosinostatin producer outcompeted sensitive conspecifics in liquid culture but not in soil, indicating that environmental context plays a key role in altering the fitness benefits of this cluster. Moreover, the competitive advantage was observed only in the presence of sensitive strains, revealing a trade-off between fitness benefits and metabolic costs. These results highlight the role of context-dependent selection in shaping the evolutionary persistence of the kosinostatin cluster. The current distribution pattern of this cluster in S. albidoflavus likely results from a dynamic interplay of intraspecific horizontal gene transfer, vertical inheritance, and recurrent gene loss. Overall, our findings establish an eco-evolutionary framework that explains the rarity of a potent antibiotic gene cluster in Streptomyces, illustrating how environmental constraints, fitness trade-offs, and gene flux collectively orchestrate the biosynthetic architecture of Streptomyces species.

Streptomyces↗

PubMed2026

Integrative Multi-Omics Analysis Identifies Thrombosis-Associated Molecular Features Linked to Germline Susceptibility and Immune Cell Communication in Gastric Cancer.

Emerging evidence indicates that coagulation-related molecular programs are associated with thrombosis, tumor progression, and molecular dysregulation in gastric cancer (GC). However, thrombosis-associated molecular features in GC and their potential links to inherited susceptibility remain insufficiently understood. Integrated analyses of transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were performed to identify thrombosis-associated genes and establish a machine learning-based prognostic signature. Genome-wide association study (GWAS), expression quantitative trait loci (eQTL), transcriptome-wide association study (TWAS), and Mendelian randomization (MR) analyses were conducted to investigate susceptibility-associated transcriptional programs in GC. Functional assays were used to evaluate candidate genes associated with malignant phenotypes. Single-cell RNA sequencing (scRNA-seq) and cell-cell communication analyses were further performed to characterize cell-type-specific expression patterns and potential intercellular interactions. A total of 22 differentially expressed thrombosis-associated genes were identified, and a prognostic signature comprising 14 genes was established. The signature stratified patients into high- and low-risk groups and showed prognostic performance in both the training and validation cohorts. Integrative GWAS, eQTL, and TWAS analyses identified susceptibility-associated transcriptional programs that were positively correlated with the thrombosis-associated risk score. Silencing ACTN2 and CRYAB significantly reduced GC cell migration and invasion. scRNA-seq analysis revealed relatively high CRYAB expression in neutrophils, and CellChat analysis suggested potential neutrophil-B cell interactions involving COLLAGEN-related signaling. This integrative multi-omics study identified a thrombosis-associated molecular signature linked to prognosis and germline susceptibility-associated transcriptional programs in GC. ACTN2 and CRYAB may represent candidate genes associated with GC cell migration and invasion, while single-cell analysis suggested potential immune-related communication features.

Humans↗