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Biomedical subjects

Ning Zhang

Publications and source records attributed to Ning Zhang.

At least 19 recordsLinked to original sources

Genome-wide characterization of NOD-like receptor genes links NLR repertoire evolution to spleen immune responses after Aeromonas hydrophila challenge in the Chinese spiny frog (Quasipaa spinosa).

NOD-like receptors (NLRs) are cytosolic pattern-recognition receptors that detect pathogen-associated and damage-associated molecular patterns and mediate innate immune signaling in vertebrates. However, the genomic repertoire, evolutionary diversification, and infection-associated expression of NLR genes remain poorly defined in non-model amphibians. In this study, 66 NLR genes were identified from the Chinese spiny frog (Quasipaa spinosa) genome and designated as QsNLR1-QsNLR66. These genes were unevenly distributed across chromosomes and were classified into three phylogenetic groups, with most members exhibiting conserved motif architectures. Gene duplication analysis indicated that dispersed duplication was the main contributor to QsNLR expansion. Synteny analysis detected five conserved orthologous gene pairs between Q. spinosa and Pelophylax nigromaculatus, suggesting partial conservation of NLR genomic organization between the two amphibians. Ka/Ks analysis showed that several duplicated gene pairs, including NLRC3-like/QsNLR36 and NLRC3-like/QsNLR50, exhibited Ka/Ks ratios greater than one, suggesting potential sequence divergence after duplication. Spleen RNA sequencing (RNA-seq) after Aeromonas hydrophila challenge revealed enrichment of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Weighted gene co-expression network analysis linked several QsNLRs to infection-associated modules, among which QsNLR57 was co-expressed with CYBB, ADAM17, SPI1, and HK2. RT-qPCR using time-matched phosphate-buffered saline (PBS) controls showed distinct temporal patterns, with stronger induction of QsNLR29, QsNLR57, and QsNLR66 and weaker or delayed responses of QsNLR50 and QsNLR56. These results characterize the NLR repertoire of Q. spinosa and identify infection-associated QsNLR candidates for future studies of antibacterial immunity in amphibians.

Animals↗

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU·mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays↗

Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4 > 0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans↗

Expression and mutation characteristics of mitochondrial genes in PBMCs of SLE patients: Implications for SLE pathogenesis.

This study aimed to investigate mitochondrial gene mutations and expression in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients, focusing on MT-ND5, and assess expression changes under lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), and dexamethasone stimulation. Peripheral blood was collected from female SLE patients. Mitochondrial DNA (mtDNA) from PBMCs was sequenced using the HiSeq PE150 platform. Quantitative reverse transcription PCR and western blotting were used to evaluate mRNA and protein expression of the most frequently mutated mitochondrial genes. Cultured PBMCs were treated with LPS, TNF-α, or dexamethasone to examine regulatory effects. A total of 589 mtDNA mutation sites were detected in SLE patients. Among 13 protein-coding genes, MT-ND5, MT-CYB, MT-CO1, MT-ND4, and MT-CO3 exhibited the highest mutation frequencies. Expression analysis revealed significantly reduced mRNA and protein levels of these genes in SLE PBMCs compared with controls, with further decreases after stimulation with LPS, TNF-α, or dexamethasone. SLE PBMCs display extensive mitochondrial mutations and downregulation of key genes, particularly MT-ND5. Inflammatory and therapeutic stimuli exacerbate this suppression, suggesting mitochondrial dysfunction contributes to SLE susceptibility and progression.

Humans↗

Adjuvant tislelizumab, lenvatinib, and capecitabine for resected biliary tract cancer: a prospective phase II trial.

BACKGROUND: This study aims to assess the efficacy and safety of a triplet adjuvant regimen consisting of tislelizumab, lenvatinib, and capecitabine following radical resection in patients with biliary tract cancer (BTC). METHODS: In this open-label, single-arm trial, patients with histologically confirmed BTC who had undergone curative resection were enrolled to receive adjuvant therapy within 4-16 weeks postoperatively. The treatment regimen consisted of tislelizumab (200 mg), lenvatinib (8 mg), and capecitabine (1250 mg/m2). The primary endpoint was the 1-year disease-free survival (DFS) rate. Secondary endpoints included median DFS, 2-year DFS rate, and 1- and 3-year overall survival (OS) rates, as well as safety profiles. Exploratory analyses were conducted to evaluate genomic alterations and prognostic biomarkers associated with clinical outcomes. RESULTS: Between February 24 and December 31, 2022, a total of 50 patients underwent treatment. As of the data cutoff (April 30, 2025), the median follow-up duration was 29.3 months (95% CI: 27.2-30.4). Intrahepatic cholangiocarcinoma constituted 78% of cases, with TNM stage III or IV observed in 40% of patients and poorly differentiated tumors identified in another 40%. The median DFS was calculated at 12.7 months (95% CI: 6.4-19.0), with DFS rates being reported as 55.5% (95% CI: 51.4%-57.6%) at 1 year and 30.8% (95% CI: 28.6%-32.9%) at 2 years, respectively. Median OS was not reached; however, the 1-year OS rate stood at an impressive figure of 93.8% (95% CI:&#x202f;91.7%-95.9%) while the 3-year OS rate declined to&#x202f;54.4% (95% CI: 50.0%-58.4%). By the exploratory analyses, FSIP2 mutation was associated shorter DFS (P&#x2009;<&#x2009;0.001). Treatment-related grade 3 adverse events occurred in 20% of patients, with no treatment-related deaths or grade&#x2009;&#x2265;&#x2009;4 toxicities reported. CONCLUSIONS: Adjuvant tislelizumab, lenvatinib, and capecitabine demonstrated clinical activity and tolerable safety in patients with resected BTC. Despite not meeting the primary endpoint, continued follow-up and further evaluation are warranted to better define the potential role of this combination regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05254847; registered prospectively on February 15, 2022.

Humans↗

Identification of Critical Genes Related to Breast Cancer with Brain Metastasis Through Bioinformatics Analysis.

INTRODUCTION: Distant metastasis accounts for the majority of Breast Cancer (BC)-related mortality. The brain is one of the most common regions of metastasis. However, the underlying molecular mechanisms remain uncertain. METHODS: In this study, gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Datasets GSE100534 and GSE52604, containing 16 primary brain tumor samples and 38 breast cancer brain metastasis samples, were used to identify the Differentially Expressed Genes (DEGs). The Metascape database was used to analyze enriched Gene Ontology (GO) entries and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway entries in DEGs. The STRING database was then used to construct a Protein-Protein Interaction (PPI) network, and the Cytoscape platform was employed to visualize the network. Furthermore, the Kaplan-Meier curve was used to analyze the Relapse-Free Survival (RFS) among the hub genes. Finally, the iRegulon plugin was used to construct a regulatory network to find the transcription factors (TFs) that regulate the expression of the hub genes. RESULTS: A total of 344 DEGs, including 182 up-regulated and 162 down-regulated genes, were identified by using the limma package in R. A module with 18 nodes and 9 hub genes was selected from the PPI network by using the plugins MCODE and Cyto- Hubba, respectively. KEGG pathway analysis demonstrated that brain metastasis in BC was closely related to the oocyte cell cycle. The Kaplan-Meier curve showed that high expression of these 9 hub genes was associated with poor RFS in BC patients. TFs' analysis showed that E2F4, SIN3A, FOXM1, and TFDP1 interacted with these hub genes. DISCUSSION: This study revealed that Breast Cancer Brain Metastasis (BCBM) may have a promoting effect on the cell cycle of oocytes and affect the maturation and division of oocytes through the KEGG and GO analyses of 344 DEGs. The selected 9 hub genes (ASPM, BUB1, BUB1B, CCNA2, CCNB1, CDK1, NDC80, NCAPG, and TOP2A) and 4 transcription factors (E2F4, SIN3A, FOXM1, TFDP1) may play a critical role in brain metastasis of BC. CONCLUSION: The results of this study may aid in the early diagnosis and suggest potential targets for the treatment of BCBM.

Brain Neoplasms↗

Effects of aerosol aging on composition and light-absorbance of nitrogen-containing organic compounds: Evidences from ultra-high-resolution mass spectrometry analysis.

Nitrogen-containing organic compounds (NOCs) are key components of particulate matter (PM), but their compositional evolution and light-absorbing properties during atmospheric aging remain poorly understood. In this study, ultra-high-performance liquid chromatography coupled with Orbitrap mass spectrometry was used to semi-quantitatively analyze 59 PM1 samples collected in Shanghai. NOCs accounted for 31 % and 64 % of the detected species in negative (ESI-) and positive (ESI+) ionization modes, respectively. Atmospheric aging significantly reduced the molecular diversity of polar organics, with both the number and mass concentration percentages of CHON- compounds showing significant negative correlations with aging degree. Van Krevelen analysis demonstrated a decrease in the number of carboxylic-rich alicyclic molecules and their CHON- contributions during the aging process (from 37.7 % in fresh samples to 21.2 % in aged samples). CHN+ compounds, a major NOCs group in ESI+ mode, also decreased with aging. Correlation analyses involving the Bep/(Bep+Bap) ratio, relative humidity, and mass absorption efficiency at 365 nm revealed a decline in light absorption capacity with aging, suggesting aqueous-phase oxidation as a dominant aging mechanism. CHON- and CHN+ compounds were identified as the principal light-absorbing constituents in PM1. This work provides new insights into the aging-induced transformations of NOCs in urban PM1, and their changing role in light absorption, highlighting the need for further investigation of the aging mechanisms of NOCs.

Aerosols↗

Natural variation of immune epitopes reveals intrabacterial antagonism.

Plants and animals detect biomolecules termed microbe-associated molecular patterns (MAMPs) and induce immunity. Agricultural production is severely impacted by pathogens which can be controlled by transferring immune receptors. However, most studies use a single MAMP epitope and the impact of diverse multicopy MAMPs on immune induction is unknown. Here, we characterized the epitope landscape from five proteinaceous MAMPs across 4,228 plant-associated bacterial genomes. Despite the diversity sampled, natural variation was constrained and experimentally testable. Immune perception in both Arabidopsis and tomato depended on both epitope sequence and copy number variation. For example, Elongation Factor Tu is predominantly single copy, and 92% of its epitopes are immunogenic. Conversely, 99.9% of bacterial genomes contain multiple cold shock proteins, and 46% carry a nonimmunogenic form. We uncovered a mechanism for immune evasion, intrabacterial antagonism, where a nonimmunogenic cold shock protein blocks perception of immunogenic forms encoded in the same genome. These data will lay the foundation for immune receptor deployment and engineering based on natural variation.

Epitopes↗

Natural variation of immune epitopes reveals intrabacterial antagonism.

Plants and animals detect biomolecules termed Microbe-Associated Molecular Patterns (MAMPs) and induce immunity. Agricultural production is severely impacted by pathogens which can be controlled by transferring immune receptors. However, most studies use a single MAMP epitope and the impact of diverse multi-copy MAMPs on immune induction is unknown. Here we characterized the epitope landscape from five proteinaceous MAMPs across 4,228 plant-associated bacterial genomes. Despite the diversity sampled, natural variation was constrained and experimentally testable. Immune perception in both Arabidopsis and tomato depended on both epitope sequence and copy number variation. For example, Elongation Factor Tu is predominantly single copy and 92% of its epitopes are immunogenic. Conversely, 99.9% of bacterial genomes contain multiple Cold Shock Proteins and 46% carry a non-immunogenic form. We uncovered a new mechanism for immune evasion, intrabacterial antagonism, where a non-immunogenic Cold Shock Protein blocks perception of immunogenic forms encoded in the same genome. These data will lay the foundation for immune receptor deployment and engineering based on natural variation.

comparative genomics↗

Fluorescence sensing and binding behavior of aminobenzenesulfonamidoquinolino-beta-cyclodextrin to Zn2+.

A water-soluble fluorescent zinc sensor which binds strongly to Zn2+ (log K = 12.4) was successfully synthesized under physiological conditions. This sensor exhibits a good fluorescence response to Zn2+ over a wide pH range in water. Under the same conditions, several metal ions commonly present in a physiological environment, such as Na+, K+, Ca2+, Mg2+, Mn2+, Fe2+, and Co2+, showed little interference to the fluorescence response to Zn2+. [structure: see text]

Binding Sites↗

Stimulation of apical and basolateral VEGF-A and VEGF-C secretion by oxidative stress in polarized retinal pigment epithelial cells.

PURPOSE: To investigate whether oxidative stress modulates vascular endothelial growth factor (VEGF)-A and VEGF-C expression and polarized secretion in a human retinal pigment epithelium cell line (ARPE-19). METHODS: Long-term culture of ARPE-19 cells in Dulbecco's modified Eagle medium (DMEM)/F12 containing 1% fetal bovine serum (FBS) on transwell filters (12 mm or 6 mm, pore size 0.4 microm) was performed to produce polarized retinal pigment epithelium (RPE) monolayers. The integrity of polarized monolayer was established by measurement of transepithelial resistance (TER) and presence of tight junctions assessed by zonula occludens (ZO-1) and occludin expression and apical Na/K ATPase localization. Paracellular permeability was studied using radiolabeled mannitol. Confluent cells were treated with tertiary butyl hydrogen peroxide (tBH) for varying durations (0-5 h) and doses (50-200 microM). VEGF-A and -C expression was evaluated by western blot and quantitative RT-PCR, while secretion to the apical and basolateral surfaces was quantitated by ELISA. RESULTS: Polarity of ARPE-19 cells was verified by the localization of tight junction proteins, ZO-1 and its binding partner occludin by confocal microscopy as well as by localization of Na,K-ATPase at the apical surface. The TER in confluent ARPE-19 cells averaged 48.7+/-2.1 Omega. cm(2) and tBH treatment (0-5 h) did not alter TER significantly (46.9+/-1.9 Omega. cm(2); p>0.05 versus controls) or ZO-1 expression. Whole cell mRNA in nonpolarized ARPE-19 increased with tBH at 5 h both for VEGF-A and VEGF-C and the increase was significant (p<0.05 vs controls). A similar, maximal increase at 5 h tBH treatment was also observed for VEGF-A and VEGF-C cellular protein levels. The secretion of VEGF-A and VEGF-C in nonpolarized ARPE showed an increase with tBH exposure. The levels of secretion of VEGF-A and -C were significantly higher in polarized monolayers and were stimulated significantly with tBH at both apical and basolateral domains. The secretion of VEGF-A increased with 150 microM of tBH treatment as a function of time (1-5 h) with maximal increases at 5 h from 410 to 2080 pg/10(6) cells on the apical and 290 to 1680 pg/10(6) cells on basolateral domains. The pattern of VEGF-C secretion was similar. VEGF-A secretion was dose-dependent for the tBH range of 50-200 microM and apical secretion tended to be higher than basolateral secretion. CONCLUSIONS: Our data show that oxidative stress to RPE from tBH upregulates secretion of both VEGF-A and C. The secretion to the apical side was higher than that of basolateral side for VEGF-A and C. Given the role of VEGF in choroidal neovascularization, these data may be of value in understanding pathogenic mechanisms and designing antiangiogenic therapies.

Cell Line↗

Analysis and design of terahertz photonic crystal fibers by an effective-index method.

An effective-index method (EIM) is used to analyze and design photonic crystal fibers (PCFs) for the terahertz radiation. By building an analogy between a conventional optical fiber and a PCF, the EIM solves the effective index of the fiber cladding and the effective modal index of a PCF analytically. The EIM is first validated by comparison with available data in the reference, showing that the role of material dispersion is negligible at higher frequencies. Terahertz PCFs with flattened dispersion are designed based on this method and the scaling property of the Maxwell equations.

Journal Article↗

Self-assembly of Co-based nanosheets into novel nest-shaped nanostructures: Synthesis and characterization.

We report the first observation of the formation of novel Co-based three-dimensional (3D) self-assembly hollow nanostructures, i.e., nest-shaped nanospheres composed of sheet-like particles, via reduction of cobalt salt with sodium tetrahydroboride in cetyltrimethylammonium bromide (CTAB)-cyclohexane-NH4F aqueous solutions. It was found that the cyclohexane has a significant influence on the formation of the nest-shaped Co-based nanospheres, because when the experiments are carried out in the absence of cyclohexane, only sheet-like particles are formed. NH4F plays also an important role in the formation of the hollow nanostructures because without this salt mainly solid spherical structures, composed of sheet-like particles, instead of nest-shaped structures are obtained. The nanostructures are mainly formed by Co, but also a minor amount (17%) of Co2B is present in the final compounds. The structures are characterized by X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), and field-emission scanning electron microscopy (FESEM). A possible mechanism for the formation of the novel Co-based nanostructures is proposed.

Journal Article↗

UniPep--a database for human N-linked glycosites: a resource for biomarker discovery.

There has been considerable recent interest in proteomic analyses of plasma for the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because the population of N-linked glycosites represents the proteomes of plasma, the cell surface, and secreted proteins at very low redundancy and provides a compelling link between the tissue and plasma proteomes. Here, we describe UniPep http://www.unipep.org--a database of human N-linked glycosites--as a resource for biomarker discovery.

Computational Biology↗

Expression of vascular endothelial growth factor-C and angiogenesis in esophageal squamous cell carcinoma.

AIM: To investigate the expression of vascular endothelial growth factor-c (VEGF-C) mRNA and microvessel density (MVD) in human esophageal squamous cell carcinoma (ESCC) and its relationship with clinical significance. METHODS: Specimens obtained from 43 patients undergoing surgical resection for ESCC were used in this study. The expression of VEGF-C mRNA was examined by in situ hybridization. Tumor MVD was determined immunohistochemically with anti-CD31 antibody and estimated by image analysis. Ten sections of adjacent normal mucosa were also examined. RESULTS: VEGF-C mRNA expression was detected in cytoplasm of carcinoma cells. Of the 43 ESCC patients studied, 18 cases (41.9%) were positive for VEGF-C mRNA. No VEGF-C mRNA expression was observed in normal esophageal mucosa. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05). Furthermore, histological grade (differentiation) tended to correlate with VEGF-C mRNA expression, but was not statistically significant (P > 0.05). In tumor lesions, the MVD was significantly greater than that in normal esophageal mucosa. MVD correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05), but not with histological grade (differentiation) (P > 0.05). Lesions with VEGF-C mRNA expression had a significantly higher MVD than that of those without VEGF-C mRNA expression (P < 0.05). CONCLUSION: VEGF-C plays a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in ESCC. VEGF-C is one of the important predictors of the biological behavior in ESCC.

Aged↗

The effect of delocalization on the exchange energy in meta- and para-linked Pt-containing carbazole polymers and monomers.

A series of novel platinum-containing carbazole monomers and polymers was synthesized and fully characterized by UV-VIS absorption, luminescence, and photoinduced absorption studies. In these compounds, a carbazole unit is incorporated into the main chain via either a para- or a meta-linkage. We discuss the effects of linkage and polymerization on the energy levels of S1, T1, and Tn. The S1-T1 splitting observed for the meta-linked monomer (0.4 eV) is only half of that in the para-linked monomer (0.8 eV). Upon polymerization, the exchange energy in the para-linked compound reduces, yet still remains larger than in the meta-linked polymer. We attribute the difference in exchange energy to the difference in wave function overlap between electron and hole in these compounds.

Journal Article↗

Secondary assembly of bile salts mediated by beta-cyclodextrin-terbium(III) complex.

A fluorescent cyclodextrin-Tb(III) complex is successfully synthesized and can include bile salts in its hydrophobic cavities. Therefore, it can efficiently induce the secondary assembly of small bile salt primary micelles to large micelle aggregates, and the aggregation process can be easily observed by transmission electron microscopy (TEM) and fluorescence microscopy.

Bile Acids and Salts↗