Biomedical subjects

Zhe Zhang

Publications and source records attributed to Zhe Zhang.

8 recordsLinked to original sources

PubMed2026

Hypoxia Response Is Associated with Reduced HPV Activity and Tumor Microenvironment Remodeling in Cervical Cancer.

Human papillomavirus (HPV) significantly influences cervical cancer progression and treatment, yet its interactions with the tumor microenvironment remain incompletely understood. We performed single-cell and spatial transcriptomic sequencing on cervical cancer samples to explore these interactions. By aligning sequencing reads to a merged HPV16-human reference genome, we characterized HPV16 heterogeneity and its association with host states at the single-cell and single-gene levels. E5 transcriptional activity was negatively associated with the host interferon response, indicating a role in immune evasion. A hypoxic environment was correlated with the downregulation of E5 activity and elevated MHC-I expression, which may contribute to stronger interactions between hypoxic cancer cells and cytotoxic CD8⁺ T cells. Additionally, HPV16 integration in host cells was associated with increased fatty acid metabolism. These findings suggest that combining anti-angiogenic drugs and fatty acid metabolism inhibitors has the potential to improve cervical cancer treatment.

Cervical cancer↗

PubMed2026

Identifying causal genetic variants for high-altitude adaptation through blood eQTL analysis in plateau populations.

A substantial number of genetic variants have been associated with high-altitude adaptation (HAA), yet most of them are located in non-coding genomic regions, leaving their specific functions and underlying mechanisms largely unknown. In this study, we analyze whole-genome and transcriptome sequencing data from a self-established cohort comprising 61 native highlanders (NHs) and 164 acclimatized newcomers (ANs), identifying 6,586 cis- and 34,203 trans-expression quantitative trait loci (eQTLs), along with 130 cell type-specific eQTLs. By further combining these data with a large East Asia (~30% Tibetan) genome-wide association study (GWAS) cohort, we employ colocalization and causal inference analyses to prioritize 85 cis-eQTLs associated with HAA and identify several novel candidate causal genes, including EXOC8, which is experimentally confirmed to regulate erythroid differentiation. Additionally, network analysis of these causal genes uncovers multiple regulatory pathways, mainly involving energy metabolism, autophagy, ubiquitination and inflammation. Our study offers a comprehensive eQTL map and reveals causal chains of "variant-gene-phenotype" for HAA-related traits, which provides new insights into potential regulatory mechanisms and targets for prevention and treatment of altitude sickness.

Quantitative Trait Loci↗

PubMed2026

ATR-dependent phosphorylation of the histone acetyltransferase HBO1 suppresses chromatin binding and promotes replication stress responses.

Mounting evidence has shown that histone acetyltransferase binding to ORC1 (HBO1) serves as an oncoprotein, warranting the use of the small molecule inhibitor WM-3835 for cancer therapy. However, HBO1 is ubiquitously expressed in both tumor and normal tissues, with potential to increase the risk of systemic toxicity. This unmet need highlights the importance of identifying suitable biomarkers to predict the sensitivity to HBO1 inhibitor. Here, we show that ATR, a key regulator of DNA replication stress, is a novel interacting partner of HBO1. In addition, we reveal a regulatory function of HBO1 in DNA replication stress responses, in an ATR-dependent manner. Mechanistically, ATR mediated HBO1 Ser50/53 phosphorylation interferes with the genomic binding of HBO1 and regulates gene expression. Notably, overexpression of HBO1 mutated at the ATR phosphorylation site (S50/53A) dampens the expression of DNA repair related genes and suppresses tumor colony formation, consistent with the observations of WM-3835 treatment. Inhibition of ATR significantly antagonized the sensitivity to WM-3835 treatment. Collectively, our findings uncovered a previously unidentified role of HBO1 in the regulation of replication stress and discovered ATR as a potential biomarker for WM-3835 treatment.

ATR↗

PubMed2026

Identification of intranasal oxytocin plasma proteome signatures.

BACKGROUND: The hypothalamic peptide oxytocin regulates a range of central and peripheral activities, ranging from uterine contractions to energy homeostasis. Oxytocin-based therapeutics are under investigation for neuropsychiatric and metabolic disease, including obesity. The mechanisms underlying oxytocin effects are poorly understood. This study profiles 4725 serum proteins in 19 healthy men across the adiposity spectrum (9 normal-weight, BMI < 25 kg/m2; 10 overweight/obese, BMI ≥ kg/m2) following exogenous, intranasal oxytocin administration to identify markers of pharmacodynamic effect. METHODS: In a double-blind, randomized controlled crossover design, 25 men were exposed to a single dose of 24 IU intranasal oxytocin vs. placebo. Fasting blood was drawn immediately prior and at 15, 30, and 55 min after oxytocin/placebo administration for proteomic analysis (SOMA Scan, Soma Logic, Inc.). RESULTS: As previously reported in the parent study, intranasal oxytocin reduced caloric intake at the test meal; here, we examined proteomic predictors of this behavioral effect. Proteomic data was available for 19 men. We identified 198 differentially expressed proteins in response to intranasal oxytocin in fasting men across the adiposity spectrum. The pathways identified are involved in intracellular signaling pathways, as well as immune regulation and inflammation. Oxytocin modulated a cluster of proteins that was associated with subsequent caloric intake at the test meal. CONCLUSIONS: These data provide insights into mechanisms underlying pharmacologic oxytocin effects on human physiology and a framework for future investigations.

Humans↗

PubMed2026

Application efficacy evaluation of the STRSeqTyper122 kit and the FASTASeq 300 second generation sequencer in kinship identification.

Forensic DNA technology is the method of choice for kinship identification. However, existing standard methods still have certain limitations in accurately determining the range of kinship relationships. China's independently developed second generation sequencing technology and equipment are expected to enhance the capability of forensic DNA kinship identification. In this study, we utilized the STRSeqTyper122 second generation sequencing STR typing kit and the FASTASeq 300 second generation sequencer to analyze 107 real kinship samples. The analysis included 63 autosomal STR loci, 42 Y-STR loci, 16 X-STR loci, and one gender-determining locus, Amel. The samples covered various kinship relationships, including 113 parent-child pairs, 48 full-sibling pairs, 76 uncle-nephew pairs, 66 grandparent-grandchild pairs, and 4 half-sibling pairs. Combined with simulated data, the ITO method was applied to calculate the cumulative likelihood ratio (CLR) for different levels of kinship based on the length polymorphism and sequence polymorphism of autosomal STR loci, systematically evaluating the practical application performance of this system in kinship identification. The results showed that, using log10CLR values of 4 and -4 as thresholds, the system achieved 100% efficiency in identifying real parent-child and full-sibling relationships. For second degree kinship identification, the system efficiency based on simulated length polymorphism data was 55.2%, while sequence polymorphism improved it to 75.11%. For real sample data, length polymorphism based efficiency was 54.45%, and sequence polymorphism based efficiency reached 76.71%. The findings indicate that the STRSeqTyper122 kit holds significant value in first degree kinship identification. Sequence polymorphism can improve second degree kinship identification efficiency to over 75%.

Humans↗

PubMed2025

Circulating inflammatory proteins as causal drivers and therapeutic targets in asthma: insights from genetic and pathway-based analyses.

OBJECTIVE: To identify circulating inflammatory proteins with potential causal roles in asthma development through integrated genetic and pathway-based analyses, and to evaluate their potential as therapeutic targets. METHODS: We used genetically anchored instrumental variables from 180 protein quantitative trait loci (pQTLs) to assess the causal effects of 91 circulating inflammatory proteins on asthma risk, using large-scale GWAS datasets. Analytical robustness was evaluated through pleiotropy and heterogeneity testing. Functional enrichment and literature-based pathway analyses were performed to support biological plausibility and validate findings. RESULTS: Four proteins showed significant causal effects on asthma: CCL19 and LIFR were protective (OR = 0.89 and 0.91, p ≤ 6.8E-03), while ARTN and IL6 were associated with increased risk (OR = 1.15 and 1.18, p ≤ 1.1E-04). We also identified reverse causal effects of asthma on 11 cytokines, including MMP10, TGFB1, IL33, and IL18R1. Most of these proteins were enriched in pathways related to cytokine signaling and immune response (p < 0.001). All identified proteins had prior literature support linking them to asthma or airway inflammation. CONCLUSIONS: Our findings highlight a subset of circulating inflammatory proteins that are likely causal in asthma pathogenesis and may serve as promising targets for therapeutic intervention. These results offer novel insights into the immunological mechanisms underlying asthma and support the utility of genetic causal inference in target prioritization.

Asthma↗

PubMed2025

Causal association between different types of ametropia and risk of diabetic retinopathy: a two-sample Mendelian randomization study.

OBJECTIVE: To investigate the causal link between ametropia and diabetic retinopathy, as well as to offer genetic support for the association between these two conditions. METHODS: This study employed a methodology involving the utilisation of genome-wide association studies data that are publicly accessible. Specifically, single nucleotide polymorphisms (SNPs) that exhibit a strong association with ametropia were employed as instrumental variables, and a two-sample Mendelian randomization (MR) approach was employed to examine the causal relationship between different types of ametropia and diabetic retinopathy. The main findings were derived from the utilisation of inverse variance weighted (IVW), while supplementary results were obtained through the utilisation of MR Egger, weighted median, simple mode and weighted mode. Additionally, a sensitivity analysis was conducted using the 'leave-one-out' method. Cochran's Q statistics were also used to quantify the heterogeneity of SNPs. RESULTS: 38 SNPs were finally included. The results of the IVW analysis indicate that myopia may exert an inhibitory effect on the development of diabetic retinopathy (OR=0.596, 95% CI (0.371, 0.957), p<0.05). Conversely, hypermetropia (OR=8.882, 95% CI (0.389×10-3, 2.06×105), p>0.05) and astigmatism (OR=1.004, 95% CI (0.888, 1.135), p>0.05) do not exhibit a causal relationship with the risk of diabetic retinopathy. CONCLUSION: This two-sample Mendelian randomization study provides evidence that myopia may impede diabetic retinopathy occurrence, while hypermetropia and astigmatism show no significant causal effects. However, our analysis treats refractive errors as independent entities, which may not reflect their clinical interdependence. Further investigations are warranted to elucidate myopia's protective mechanisms.

Humans↗

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↗