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Biomedical subjects

Kai Huang

Publications and source records attributed to Kai Huang.

5 recordsLinked to original sources

LINC01871-Mediated Sensitivity to Cyclin-Dependent Kinase 4/6 Inhibitors in Human Breast Cancer.

Breast cancer remains the most frequently diagnosed malignancy in women, and resistance to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors limits long-term treatment efficacy. This study aimed to identify long non-coding RNAs (lncRNAs) associated with predicted sensitivity to CDK4/6 inhibitors and to investigate their biological functions in breast cancer. Transcriptomic data from The Cancer Genome Atlas (TCGA) and drug sensitivity data from the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) database were integrated, and drug sensitivity was predicted using the oncoPredict algorithm. Candidate lncRNAs were identified through differential expression analysis, weighted gene co-expression network analysis, prognostic analysis, and machine learning. The biological functions of LINC01871 were subsequently evaluated using in vitro and in vivo experiments. Sixty-two lncRNAs associated with predicted sensitivity to ribociclib and palbociclib were identified, and six core lncRNAs were selected. LINC01871 showed the highest discriminatory performance for predicted drug sensitivity. Overexpression of LINC01871 was associated with increased sensitivity of breast cancer cells to ribociclib and palbociclib, inhibition of cell proliferation, promotion of apoptosis, and suppression of nuclear factor kappa B (NF-κB) signaling. Single-cell transcriptomic analysis demonstrated high LINC01871 expression in T cells and natural killer (NK) cells, while transcriptome-based immune infiltration analyses showed that high LINC01871 expression was associated with increased immune infiltration. These findings identify LINC01871 as a candidate biomarker of sensitivity to CDK4/6 inhibitors and demonstrate its tumor-suppressive effects in breast cancer. Further clinical and mechanistic studies are required to validate its predictive value and therapeutic relevance.

Humans

The Spatiotemporal Genetic Architecture of Seed Vigor in Upland Cotton.

Seed vigor underpins uniform crop establishment, but its dynamic genetics are understudied. Combining high-resolution temporal phenotyping and genomics in upland cotton, we used the SeedRanger platform to record 17 image-based traits every 30 min over 120 h, revealing stage-specific heritability and identifying 541 seed-vigor loci. These loci show extensive pleiotropy and temporal coordination, forming a genetic network that preserves developmental continuity; 8.9% overlap regions under domestication selection, indicating concurrent optimization with fiber yield. Functional validation of FLA2, a candidate gene underlying a dynamic QTL, implicates auxin-mediated control of radicle elongation and cotyledon development. This temporal framework exposes dynamic genetic architecture and breeding targets for high-vigor crops.

Gossypium

Construction of precision clinical-proteomics risk model based on machine learning for predicting heart failure in type II diabetes mellitus.

BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.

Humans

Long-Term Warming Reduces Bacterial Diversity and Functional Potential in Temperate Forest Soil.

Soil microbes are key regulators of forest carbon cycling, yet how their diversity and functional potential respond to long-term warming remains poorly understood. Here, we report a five-year in situ warming experiment in a temperate forest, combining ten repeated measurements of microbial diversity and functional gene potential, as well as continuous monitoring of soil CO2 flux. We found that warming progressively reduced bacterial diversity and induced phylogenetically conserved community reorganization. Under warming, community composition shifted in a phylogenetically conserved manner. Warming generally reduced the abundance of microbial functional genes across most carbon-, nitrogen-, and phosphorus-cycling gene categories, except for genes associated with starch decomposition. Warming also altered the factors associated with soil CO2 flux: microbial diversity showed a stronger association with soil CO2 flux under long-term warming, whereas soil moisture was the dominant predictor in the control treatment. This warming-enhanced biodiversity control over soil CO2 flux was associated with shifts in microbial functional potential, particularly increases in starch-degrading genes and microbial biomass production potential. Together, our results suggest that warming can restructure microbial communities in ways that strengthen biodiversity-dependent regulation of soil carbon cycling, with implications for climate-carbon feedbacks.

Soil Microbiology

Genetic targets related to aging for the treatment of coronary artery disease.

BACKGROUND: Coronary Artery Disease (CAD) is the most common cardiovascular disease worldwide, threatening human health, quality of life and longevity. Aging is a dominant risk factor for CAD. This study aims to investigate the potential mechanisms of aging-related genes and CAD, and to make molecular drug predictions that will contribute to the diagnosis and treatment. METHODS: We downloaded the gene expression profile of circulating leukocytes in CAD patients (GSE12288) from Gene Expression Omnibus database, obtained differentially expressed aging genes through "limma" package and GenaCards database, and tested their biological functions. Further screening of aging related characteristic genes (ARCGs) using least absolute shrinkage and selection operator and random forest, generating nomogram charts and ROC curves for evaluating diagnostic efficacy. Immune cells were estimated by ssGSEA, and then combine ARCGs with immune cells and clinical indicators based on Pearson correlation analysis. Unsupervised cluster analysis was used to construct molecular clusters based on ARCGs and to assess functional characteristics between clusters. The DSigDB database was employed to explore the potential targeted drugs of ARCGs, and the molecular docking was carried out through Autodock Vina. Finally, single-cell data (GSE159677) of arterial intima was used to further explore the expression of aging signature genes in different cell subpopulations. RESULTS: We identified 8 ARCGs associated with CAD, in which HIF1A and FGFR3 were up while NOX4, TCF7L2, HK3, CDK18, TFAP4, and ITPK1 were down in CAD patients. Based on this, CAD patients can be divided into two molecular clusters, among which cluster A mainly involves functional pathways such as ECM receptor interaction and focal adhesion; cluster B mainly involves functional pathways such as amimo sugar and nucleotide sugar metabolism and pyrimidine metabolism. In addition, the molecular docking results showed that retinoic acid and resveratrol had good binding affinity with targets genes. Further single-cell analysis results showed that NOX4, TCF7L2, ITPK1, and HIF1A were specifically expressed in different types of cells in atherosclerotic tissues. CONCLUSION: Our study identified several ARCGs that may be involved in the pathogenesis and progression of CAD. Further, retinoic acid and resveratrol were potential candidate molecule drugs for inhibiting these targets.

Humans