Biomedical subjects

Xinyu Wang

Publications and source records attributed to Xinyu Wang.

At least 19 recordsLinked to original sources

PubMed2026

Sex modifies the association of high-altitude hypoxia with poor sleep quality and depression in school-age children and adolescents.

BACKGROUND: While chronic exposure to high-altitude hypoxia is known to impair sleep and mental health, whether these effects are sex-dependent remains unclear. This study addresses a critical gap by investigating how sex modifies the association between high-altitude hypoxia and risks of poor sleep quality, depressive symptoms, and their co-occurrence in children and adolescents. METHODS: In this cross-sectional study (March-May 2024), we enrolled 1,345 long-term residents of the Shannan Tibet Autonomous Prefecture (altitude: 3,650-4,800 m) and 2,909 age-matched controls from low-altitude plains (Anhui Province, China). Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Montgomery-Asberg Depression Rating Scale (MADRS), respectively. Sex-stratified analyses and interaction metrics (RERI/AP/SI) were employed to evaluate additive and multiplicative effects. RESULTS: High-altitude residents exhibited significantly higher prevalence of poor sleep (24.2% vs. 18.7%, P < 0.001), depression (23.6% vs. 15.3%, P < 0.001), and their co-occurrence (12.6% vs. 8.6%, P < 0.001) compared to low-altitude controls. A significant negative additive interaction (RERI = - 0.78, 95% CI: -1.35 to - 0.3; P < 0.001) indicated that sex modifies the altitude-outcome association. Specifically: (1) high-altitude residence significantly increased poor sleep risk in males (OR = 1.60, 95% CI: 1.26-2.03) but not in females (OR = 1.39, 95% CI: 1.07-1.79); and (2) the expected female predominance in poor sleep observed in the plain region (OR = 1.452, 95% CI: 1.191-1.769) disappeared in the plateau region (OR = 0.865, 95% CI: 0.667-1.121). Similar patterns were independently replicated for depressive symptoms. These findings confirm that high-altitude exposure differentially increases risk in males rather than protecting females. CONCLUSION: Males show marked vulnerability to high-altitude-associated sleep and mood impairments, while females demonstrate resilience. Sex-tailored interventions for high-altitude populations, particularly targeting male adolescents, are urgently needed.

Humans↗

PubMed2026

HNRNPC as a Novel Therapeutic Target for Ischemic Heart Disease: Evidence From Mendelian Randomization and Experimental Validation.

BACKGROUND: Several studies have suggested that N6-methyladenosine (m6A) plays an essential role in cardiovascular disease, but the causality of m6A on ischemic heart disease (IHD) remains unknown. Therefore, this study investigated the potential relationship between m6A and IHD using a 2-sample Mendelian randomization method. METHODS: The publicly available genome-wide association study data for m6A-related proteins were obtained from the INTERVAL study, a large population-based cohort of healthy blood donors in the United Kingdom, whereas the genome-wide association study database (including 30 952 cases and 187 840 healthy controls) provided the IHD data. We performed a 2-sample Mendelian randomization analysis to evaluate the potential causal association between HNRNPC (heterogeneous nuclear ribonucleoprotein C) and IHD, followed by experimental validation in vitro and in vivo to confirm the role of HNRNPC in IHD pathogenesis. RESULTS: There was no indication of pleiotropy or heterogeneity among the 6 m6A-associated proteins, but Mendelian randomization analysis revealed that HNRNPC (odds ratio [OR], 0.93 [95% CI, 0.88-0.97]; P=0.002) was associated with IHD. When IHD developed, there was a significant upregulation of HNRNPC expression in both animal and cellular tests. HNRNPC knockdown prevented oxidative stress, mitochondrial dysfunction, and cell death. CONCLUSIONS: The Mendelian randomization study suggests a potential causal association of the m6A-related protein HNRNPC in the cause of IHD and verified the accuracy of the results through a series of experiments, which will help us understand the pathogenesis of IHD and identify potential therapeutic targets in the future.

Humans↗

PubMed2026

Chromosome-level genome assembly of the small-sized Taihang donkey (Equus asinus).

China harbors a rich diversity of donkey breeds, with small-sized donkeys (<110 cm) representing a largely underexplored group. Here, we present the first high-quality, chromosome-level genome assembly of a small-sized donkey, generated using PacBio HiFi sequencing (286.7 Gb), Hi-C scaffolding (240.47 Gb), and annotated with RNA-seq data. The final assembly has a total length of 2.7 Gb and comprises 32 chromosomes (including both X and Y chromosomes), in which five chromosomes were fully assembled without gaps. It possesses a scaffold N50 of 106.70 Mb and 84 contigs (contig N50 = 63.60 Mb), and captures 99.2% of BUSCO genes. The assembly achieved a consensus quality value (QV) of 77.44, corresponding to an extremely low base-level error rate, indicating exceptional nucleotide accuracy. This high-quality genome provides a valuable resource for investigating genetic variation, adaptive evolution, and domestication processes in small-sized donkeys, and will facilitate the conservation and sustainable utilization of rich donkey genetic resources in China.

Animals↗

PubMed2026

Enzymatic innovations in Angelica pubescens reveal dual coumarin biosynthetic pathways driving metabolic diversification.

Coumarins are structurally diverse phenylpropanoid derivatives with ecological and pharmacological significance, yet the biosynthetic logic underlying their diversification remains incompletely understood in non-model medicinal plants. Angelica pubescens (Apiaceae), widely used in traditional Chinese medicine, accumulates a rich repertoire of furanocoumarins and dihydrofuranocoumarins, making it an ideal system to investigate this metabolic complexity. Here, we combined chromosome-level genome assembly, transcriptome and metabolite profiling, phylogenetics, and heterologous expression assays to dissect coumarin biosynthesis in A. pubescens. We identified two functionally specialized O-methyltransferases, ApOMT1 and ApOMT2, which catalyze regioselective methylation of xanthotoxol and bergaptol to yield the furanocoumarins xanthotoxin and bergapten. We also characterized ApCYP736A121, a cytochrome P450 enzyme that converts osthenol to the dihydrofuranocoumarin columbianetin via a previously unknown mechanism. Gene expression and metabolite accumulation patterns across tissues and developmental stages revealed functional partitioning among pathway branches. Phylogenetic and syntenic analyses indicated that ApOMT1 and ApOMT2 arose through subfunctionalization following gene duplication, whereas ApCYP736A121 evolved via neofunctionalization from a distantly related CYP736 ancestor. Together, our findings uncover dual biosynthetic routes to structurally distinct coumarins in A. pubescens and provide insights into the evolutionary mechanisms contributing to metabolic innovation in Apiaceae. This work lays a foundation for future efforts to engineer coumarin pathways and understand their ecological functions in medicinal plants.

Coumarins↗

PubMed2026

Quantitative Proteomic Analysis of APP/PS1 Transgenic Mice.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD. OBJECTIVE: The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD. METHODS: To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts. RESULTS: Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks. CONCLUSIONS: This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.

Animals↗

PubMed2025

A New Allele HLA-DQB1*06:02:01:42 Identified by HLA-Targeted Third-Generation Sequencing in a Chinese Individual.

HLA-DQB1*06:02:01:42 differs from HLA-DQB1*06:02:01:01 by one nucleotide change in intron 1.

Humans↗

PubMed2006

Sonochemical preparation of hydroxyapatite nanoparticles stabilized by glycosaminoglycans.

Stable hydroxyapatite (HAP) nanoparticles system was synthesized from Ca(H(2)PO(4))(2) aqueous solution and saturated Ca(OH)(2) aqueous solution by an improved precipitation method. This method was reformed through using ultrasound irradiation as assistant technology due to its unique chemical reaction effects and adding glycosaminoglycans (GAGs) as regulation additive due to its strong interaction with HAP. The products were characterized by Malvern Zetasizer 3000HS Analysis system, TEM and ED. The size distribution and zeta potential of HAP nanoparticles were influenced by the concentration of GAGs. With the GAGs concentration of 0.35g/L, the better excellent HAP nanoparticle system could be obtained with the number-averaged particle size of 22.2nm in 84.5% area and 54.6nm in 15.5% area between 18.1nm and 117.4nm and the zeta potential of -60.9mV. In the presence of GAGs, the particle size and size distribution are little sensitive to the ultrasound irradiation (UI) time. With the increasing of UI time from 0.5h to 3h and 5h, the particle size increased a little and the crystallinity was improved. GAGs inhibited HAP crystal growth and stabilized HAP nanoparticles. Based on the TEM observation and size distribution determination of HAP nanoparticles, the possible formation mechanism of HAP nanoparticles stabilized by GAGs under UI was discussed.

Biocompatible Materials↗

PubMed2006

Cell-based screening and validation of human novel genes associated with cell viability.

In the present study, a cell-based high-throughput assay is established to identify novel human genes associated with cell viability. The assay relies on the down-regulation of Renilla luciferase (pRL) activity in a 96-well format. In addition, 2-color fluorescence probes were used to distinguish living and dead cells. As the positive control, the authors used the expression vectors encoding Bax, TNFRSF1A, and TAJ, which were widely known to effectively induce programmed cell death. They screened 409 novel genes (including alternative mRNA splicing forms) cloned in their laboratory and found that 39 genes could significantly down-regulate pRL activity. A subsequent fluorescence-based assay revealed that 4 of the 39 genes (PIP5KL1, OLFM1, RNF122, FAM26B) were associated with cell viability. Further function assays validated that the 4 genes were able to induce both necrosis and apoptosis. These results therefore indicate that a rapid and effective screening system has been developed, which should shed light on some functions of novel genes.

Apoptosis↗

PubMed2006

Cytoprotective effect of caffeic acid phenethyl ester (CAPE) and catechol ring-fluorinated CAPE derivatives against menadione-induced oxidative stress in human endothelial cells.

Caffeic acid phenethyl ester (CAPE), a natural polyphenolic compound with many biological activities, has been shown to be protective against ischemia-reperfusion injury. We have synthesized six new catechol ring-fluorinated CAPE derivatives and evaluated their cytotoxic and cytoprotective effects against menadione-induced cytotoxicity in human umbilical vein endothelial cells. These results provide some insights into the structural basis of CAPE cytoprotection in this assay, which does not appear to be based solely on direct antioxidant properties.

Antioxidants↗

PubMed2005

Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor.

In utero exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the active component from marijuana, induces cognitive deficits enduring into adulthood. Although changes in synaptic structure and plasticity may underlie Delta(9)-THC-induced cognitive impairments, the neuronal basis of Delta(9)-THC-related developmental deficits remains unknown. Using a Boyden chamber assay, we show that agonist stimulation of the CB(1) cannabinoid receptor (CB(1)R) on cholecystokinin-expressing interneurons induces chemotaxis that is additive with brain-derived neurotrophic factor (BDNF)-induced interneuron migration. We find that Src kinase-dependent TrkB receptor transactivation mediates endocannabinoid (eCB)-induced chemotaxis in the absence of BDNF. Simultaneously, eCBs suppress the BDNF-dependent morphogenesis of interneurons, and this suppression is abolished by Src kinase inhibition in vitro. Because sustained prenatal Delta(9)-THC stimulation of CB(1)Rs selectively increases the density of cholecystokinin-expressing interneurons in the hippocampus in vivo, we conclude that prenatal CB(1)R activity governs proper interneuron placement and integration during corticogenesis. Moreover, eCBs use TrkB receptor-dependent signaling pathways to regulate subtype-selective interneuron migration and specification.

Animals↗

PubMed2005

Overexpression of the novel human gene, nuclear apoptosis-inducing factor 1, induces apoptosis.

Apoptosis is a genetically determined cell suicidal program that plays critical roles in many physiological and pathological processes. In this study, we report the cloning and characterization of a novel human gene, nuclear apoptosis-inducing factor 1 (NAIF1), overexpression of which induces apoptosis in cells. Human NAIF1 is located on chromosome 9q34.11 and encodes 327 amino acids with a homeodomain-like region and two nuclear localization signals at its N-terminal region. NAIF1 is conserved across diverse species, including human, mouse, crab-eating macaque, dog, chicken and frog, and shares no obvious homology to any known genes or proteins. Northern blot analysis revealed wide expression of NAIF1 mRNA throughout human tissues. NAIF1 was predominantly localized in the nucleus. Overexpression of NAIF1 inhibited cell growth and induced apoptosis. Furthermore, NAIF1 transfection caused both decreases in mitochondrial membrane potential and caspase-3 activation. In summary, NAIF1 is a nuclear protein that induces apoptosis when overexpressed.

Active Transport, Cell Nucleus↗

PubMed2005

Relationship between parameters of bacteriorhodopsin film and behavior of optical novelty filters.

To continue our earlier research on novelty filters in a system of incoherent light [Opt. Lett. 30,81 (2005)], we discuss the relationship between parameters of a bacteriorhodopsin film and the quality of a novelty filter image. For both fixed and moving velocities of the input image, differences in the novelty filter's image as a function of thickness, lifetime of the M state, and molecular concentration are displayed, and the optimal ranges of parameters of the bR film that correspond to the entire novelty filter image and obvious gray-level differences in the image are given. The method can be used to design high-quality novelty filter images in incoherent light systems.

Bacteriorhodopsins↗

PubMed2004

In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus.

BACKGROUND: Marijuana (Cannabis sativa) is the illicit drug most used by pregnant women, and behavioral and cognitive impairments have been documented in cannabis-exposed offspring. Despite the extensive use of marijuana, very limited information exists as to the consequences of prenatal cannabis exposure on the developing human brain. METHODS: We optimized an in situ hybridization histochemistry technique to visualize mRNA expression in midgestation (weeks 18-22) human fetal specimens from mothers with and without documented evidence of cannabis use during pregnancy. The cannabinoid receptor type 1 (CB(1)) and major dopamine receptor subtypes, D(1) and D(2), were examined in the striatum and mesocorticolimbic structures (amygdala and hippocampus). RESULTS: Adjusting for various covariates, we found a specific reduction, particularly in male fetuses, of the D(2) mRNA expression levels in the amygdala basal nucleus in association with maternal marijuana use. The reduction was positively correlated with the amount of maternal marijuana intake during pregnancy. No significant cannabis-related alterations were detected in the hippocampus or caudal striatum for the D(2), D(1), and CB(1) mRNA levels, although alcohol showed significant contribution to striatal D(1)/D(2) expression. CONCLUSIONS: These human fetal findings suggest that in utero cannabis exposure may impair distinct mesocorticolimbic neural systems that regulate emotional behavior.

Adult↗

PubMed2004

Cell type-specific gene expression, mediated by TFL-3, a cationic liposomal vector, is controlled by a post-transcription process of delivered plasmid DNA.

The issue of whether the TFL-3, a recently developed cationic liposome, achieves efficient gene expression in different mammalian cell lines (NIH/3T3, LLC, A431 and HeLa cells) was examined. The issue of whether gene expression is related to the amount of plasmid DNA (pDNA) delivered in cells or nuclei following transfection was also examined. The cells were transfected for 1h with pDNA/TFL-3 lipoplexes, and the transfection efficiency was determined by means of a luciferase activity assay. The amount of intracellular and intranuclear pDNA following the transfection was also quantitatively determined. Successful transgene expressions in all cell lines we tested were observed under our experimental conditions, suggesting that the TFL-3 represents a suitable nonviral vector system for the successful gene expression in mammalian cells in vitro. The degree and rate of gene expression were dependent on the type of cells used as well as the incubation time after transfection, but these parameters were independent of the amount of gene delivered to cells and nuclei. These results suggest that TFL-3 mediated gene expression is largely controlled by the process of post-transcription of the delivered pDNA, and not by the process of cellular entry of pDNA and cytoplasmic trafficking of pDNA into nuclei, which is dependent on the cell type. Therefore, the results obtained here clearly suggest that the cell type-specific improvement in transcription efficiency of pDNA and translation of the derived mRNA, together with an improved delivery system to enhance the nuclear delivery of pDNA, is necessary to achieve efficient transgene expression in mammalian cells.

Animals↗

PubMed2004

Histone H1-like protein participates in endothelial cell-specific activation of the von Willebrand factor promoter.

A region of the von Willebrand factor (VWF) promoter has been identified that is necessary to confer endothelial cell-specific activation to the VWF promoter. This region spans sequences +155 to +247 and contains binding sites for GATA6 and NFY transcription factors. To identify potential DNA binding transcription factors that directly interact with these sequences in an endothelial-specific manner, we have performed extensive gel mobility assays with use of 7 overlapping DNA probes that collectively span this entire region. An endothelial-specific protein DNA complex was formed with an oligonucleotide that corresponded to sequences +155 to +184 of the VWF gene. Mutation analysis identified a 6-nucleotide element corresponding to sequences +164 to +169 as the core-binding region for the formation of this complex. Transfection analysis demonstrated that the mutation, which abolished DNA-protein interaction, resulted in significant inhibition of the VWF promoter activity. DNA pull-down analysis, mass spectrometry, and Western blot analysis demonstrated that a 32-kDa polypeptide with homology to histone H1 constituted the endothelial-specific DNA binding protein, or a DNA binding subunit of this protein complex. On the basis of these results, we hypothesize that an H1-like protein functions as an endothelial cell-specific transcriptional activator of the VWF promoter.

Amino Acid Sequence↗

PubMed2004

Analysis of capillary interferometry for measuring refractive indices of minute samples.

A method of measuring the refractive indices of minute samples by analyzing capillary interferometry is introduced. With the interference theory of light, the intensity distribution of an interference fringe pattern formed by a cylindrical tube of a capillary is obtained, and the influence of some parameters on the fringes are discussed. The measurement accuracy and its relative problems are analyzed.

Journal Article↗

PubMed2003

Measurement and analysis of light distribution in intralipid-10% at 650 nm.

A method for measuring the distributions of light in the biological tissue phantom Intralipid by use of an optical fiber is presented and measurements of distributions of light in Intralipid-10% suspensions at 650 nm are described. This approach is complementary to that in which an optical fiber with an isotropic tip detects the distribution of light in tissue phantoms. The characteristics of the distance-dependent intensity of scattering light in different directions were revealed by the experimental results; the effects of the optical parameters and of the radius of the incident beam on the distributions of light in tissue phantoms were given; and the experimental results were analyzed by the diffusion theory. These studies will help in further understanding of the scattering characteristics of tissue.

Diffusion↗

PubMed2003

Cell-based and direct gene transfer-induced angiogenesis via a secreted chimeric fibroblast growth factor-1 (sp-FGF-1) in the chick chorioallantoic membrane (CAM).

Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor; its structure lacks a signal peptide for secretion. We previously reported that the overexpression of a secreted version of FGF-1 (sp-FGF-1) in microvascular endothelial cells (ECs) enhances cell migration [Partridge et al. J Cell Biochem 2000; 78(3): 487]. In the current study, we have examined the angiogenic effects of sp-FGF-1 in chicken chorioallantoic membranes (CAMs). Two methods of examining the effects of sp-FGF-1 in CAMs were used: cell-mediated transfection via bovine ECs and direct gene transfection. In the cell-mediated gene transfection, those eggs that were implanted with a gelatin sponge seeded with ECs stably transfected to over-express sp-FGF-1 protein showed a significant increase in angiogenesis inside the sponge when compared to eggs treated with vector control-transfected ECs. In the direct gene transfer, eggs received sp-FGF-1 showed a significant increase in vascularization when compared to eggs received vector alone plasmids. These CAM models are useful both for studying molecular mechanisms of angiogenesis and for developing better gene therapy strategies.

Allantois↗