Biomedical subjects

Ying Xu

Publications and source records attributed to Ying Xu.

10 recordsLinked to original sources

PubMed2026

The genetic overlap between schizophrenia and major depression with cognitive function.

This study aimed to systematically dissect the shared genetic basis of schizophrenia (SCZ) and major depression (MD) with cognitive function. To investigate this, we integrated large-scale genome-wide association studies (GWAS) summary statistics for SCZ (N = 175,799, [cases, 74,776; controls, 101,023]), MD (N = 2,622,273 [cases, 550,355; controls, 2,071,918]) and four cognitive traits (reaction time, N = 330,069; memory, N = 112,067; verbal-numerical reasoning, N = 36,035; educational attainment, N = 111,114). Linkage disequilibrium (LD) score regression analysis revealed that SCZ showed significant negative genetic correlations with reaction time, memory, and verbal-numerical reasoning. MD showed negative genetic correlations with memory, verbal-numerical reasoning, and educational attainment. Bayesian colocalization analysis identified seven genomic regions with strong or supportive evidence between SCZ and cognitive function, and two genomic regions with supportive evidence between MD and cognitive function. Gene mapping and over representation analysis (ORA) indicated that SCZ-associated genes were primarily involved in pathways related to transport processes, and MD-associated genes were significantly enriched in pathways related to neural development. Through genetic correlation and colocalization analysis, this study elucidates the genetic overlap between SCZ and MD with cognitive function, providing a new perspective for related research.

Journal Article↗

PubMed2026

Identification of a Novel Thermal Promoter and Its Application in Glutamate Decarboxylase Protein Expression in Bacillus licheniformis.

As a thermotolerant bacterium, Bacillus licheniformis is an attractive chassis for high-temperature biomanufacturing. Here, we identified a novel temperature-responsive promoter, PycgM, which maintained strong transcriptional activity at 37-52 °C. In a promoter-mCherry reporter system, PycgM exhibited 2287.3-fold higher activity than P2 at 52 °C, demonstrating excellent compatibility with a thermotolerant host. Truncation analysis identified a 150-bp core functional region responsible for optimal activity under induction and heat stress. When applied to drive glutamate decarboxylase expression at 50 °C, PycgM enabled γ-aminobutyric acid production of 391.67 g/L with a 98.69% conversion rate, representing a 275% increase over 37 °C fermentation. The whole-cell biocatalyst retained 86% activity after five reuse cycles, and SEM analysis indicated acceptable structural stability despite moderate morphological changes. These results demonstrate that PycgM is a robust, high-temperature genetic element for efficient enzyme and metabolite production in thermotolerant hosts.

Bacillus licheniformis↗

PubMed2026

Human GPR174 deficiency drives polyclonal lymphoproliferative disease via defects in T cell function.

The X-linked G-protein coupled receptor GPR174 is highly expressed in T and B lymphocytes and has immunoregulatory roles in mice, but its function in humans is unknown. We describe a cohort of six individuals who have function-disrupting variants in GPR174 and a clinical phenotype of lymphadenopathy and autoimmunity. Histological analysis of two patient lymph nodes revealed necrotizing lymphadenitis and lymphoproliferation resembling Kikuchi-Fujimoto disease. In-depth analysis of three patients and related carriers revealed overaccumulation of CD8 terminally differentiated effector memory cells re-expressing CD45RA (TEMRA). Patient cells and GPR174-deficient CD8 T cells generated from controls showed less repression of proliferation by the GPR174 ligand lysophosphatidylserine (lysoPS) and an effector-biased gene expression program. GPR174-deficient CD4 T cells were resistant to lysoPS-mediated suppression of IL2 production. In mice, chronic viral infection led to over-accumulation of GPR174-deficient effector CD8 T cells. We describe an inborn error of immunity associated with dysregulated lymphocyte responses that we propose predisposes to exaggerated lymphoproliferation and autoimmunity following viral infection.

Journal Article↗

PubMed2026

Targeting pancreatic cancer progression: The formononetin and salvianolic acid B combination suppresses JAK/STAT signaling via MBOAT2 downregulation.

OBJECTIVE: Formononetin and salvianolic acid B (FcS) are the primary bioactive components of the Astragalus mongholicus-Salvia miltiorrhiza herbal pair, a classic combination for treating pancreatic cancer associated with qi deficiency and blood stasis. This study elucidates the therapeutic potential and mechanisms of FcS in the treatment of pancreatic cancer. METHODS: A zebrafish xenograft model was used to screen bioactive combinations derived from A. mongholicus and S. miltiorrhiza, identifying FcS as a candidate with antitumor activity. Its efficacy was evaluated in vivo using the zebrafish model, orthotopic LSL-KrasG12D/+, LSL-Trp53R172H/+ and Pdx-1-Cre (KPC) mice, and subcutaneous xenograft models. Cell viability and proliferation were assessed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine and colony formation assays, and migration and invasion were evaluated by wound healing and transwell assays. Membrane-bound O-acyltransferase 2 (MBOAT2) was identified as a potential target through a molecular docking study and the Cancer Genome Atlas (TCGA) analysis. MBOAT2 knockdown cells were used to explore its roles and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in FcS-mediated inhibition. RESULTS: In the zebrafish model, FcS strongly inhibited pancreatic tumor growth. FcS reduced tumor volume, the expression of proliferation marker Ki-67, and proliferating cell nuclear antigen in KPC mice. In vitro, FcS inhibited pancreatic cancer cell viability, proliferation, migration and invasion, which was accompanied by downregulation of MBOAT2 expression. TCGA analysis linked high MBOAT2 expression to aggressive phenotypes. MBOAT2 knockdown reduced the survival, proliferation and invasion of BxPC-3 cells. Rescue experiments revealed that MBOAT2 knockdown attenuated the antitumor effects of FcS, possibly through modulation of the JAK/STAT signaling pathway. FcS also inhibited tumor proliferation in xenograft models, and MBOAT2 expression was elevated in tumor tissues from pancreatic cancer patients. CONCLUSION: FcS suppresses pancreatic cancer progression via MBOAT2 downregulation and JAK/STAT pathway inhibition, which highlights MBOAT2 as a potential therapeutic target. Please cite this article as: Xu Y, Xu CS, Jin HB, Gu WG, Shen HZ, Lu L, Chen Y, Xu DC, Zhang XF, Yang JF, Wang Y. Targeting pancreatic cancer progression: The formononetin and salvianolic acid B combination suppresses JAK/STAT signaling via MBOAT2 downregulation. J Integr Med. 2026; 24(5):725-741.

Animals↗

PubMed2025

The suprachiasmatic nucleus regulates brown fat thermogenesis in male mice through an adrenergic receptor ADRB3-S100B signaling pathway.

The suprachiasmatic nucleus (SCN), the central circadian pacemaker, orchestrates daily metabolic rhythms, yet its role in substrate selection and thermogenic adaptation under stress remains insufficiently understood. Here, we show that SCN lesioning abolishes the adaptive suppression of brown adipose tissue (BAT) thermogenesis typically observed during time-restricted feeding in subthermoneutral environments (TRF-STE), a paradigm that imposes concurrent nutrient and thermal stress. Contrary to wild-type responses, SCN-lesioned mice maintain elevated BAT thermogenic activity, despite impaired lipolysis, instead shifting toward glucose-driven heat production. This phenotype is accompanied by sustained sympathetic tone and β3-adrenergic receptor (ADRB3) signaling in BAT. Mechanistically, we identify a SCN-regulated ADRB3-S100B signaling axis underlying this metabolic reprogramming. S100B, a nutrient-sensitive calcium-binding protein, is upregulated in BAT following SCN disruption, where it promotes thermogenesis by stimulating brown adipocyte proliferation and suppressing senescence. Functional studies reveal that S100B is both necessary and sufficient for sustaining BAT thermogenesis under TRF-STE. Furthermore, diverse SCN disruption models, including light-induced circadian arrhythmia, N-Methyl-D-aspartic acid (NMDA) excitotoxicity, and Caspase-3-mediated ablation, consistently elevate S100B expression in BAT, reinforcing its role as a convergent effector of SCN-regulated metabolic adaptation. Thus, in intact animal, the SCN restrains the ADRB3-S100B module, gating BAT thermogenic output in accordance with energetic availability. Disruption of SCN output lifts this restraint, unmasking a latent ADRB3-S100B program that preserves thermogenesis when lipid fuel is limited. These findings reveal a previously unrecognized role of the SCN in governing thermogenic flexibility and fuel partitioning, and position the ADRB3-S100B axis as a potential target for mitigating circadian misalignment and metabolic disease.

Animals↗

PubMed2025

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect↗

PubMed2025

Phenotypic pleiotropy of missense variants in human B cell confinement receptor P2RY8.

Missense variants can have pleiotropic effects on protein function, and predicting these effects can be difficult. We performed near-saturation deep mutational scanning of P2RY8, a G protein-coupled receptor that promotes germinal center B cell confinement. We assayed the effect of each variant on surface expression, migration, and proliferation. We delineated variants that affected both expression and function, affected function independently of expression, and discrepantly affected migration and proliferation. We also used cryo-electron microscopy to determine the structure of activated, ligand-bound P2RY8, providing structural insights into the effects of variants on ligand binding and signal transmission. We applied the deep mutational scanning results to both improve computational variant effect predictions and to characterize the phenotype of germline variants and lymphoma-associated variants. Together, our results demonstrate the power of integrating deep mutational scanning, structure determination, and in silico prediction to advance the understanding of a receptor important in human health.

Humans↗

PubMed2025

Surveillance of tick-borne viruses in the border regions of the Tumen River Basin: Co-circulation in ticks and livestock.

BACKGROUND: The unique eco-geographical patterns and climatic conditions of the China-Tumen River border region, combined with frequent cross-border tourism and trade activities, collectively establish this area as a recognized hotspot for tick-borne disease outbreaks. However, critical knowledge gaps persist regarding the eco-epidemiology of emerging tick-borne viruses and the distribution of their potential reservoir hosts within this trinational ecosystem spanning China, North Korea, and Russia. METHODS: We collected a total of 2,004 ticks from the study area, along with blood samples obtained from 42 sheep and 45 cattle. Following viral metagenomic analysis of the ticks, dual verification of target pathogens in all samples was performed using qRT-PCR and RT-PCR assays. Phylogenetic trees were constructed and nucleotide sequences were analyzed to delineate relationships between the obtained virus strains and reference sequences. RESULTS: Viral metagenomics identified three viruses in ticks: Dabieshan tick virus (DBTV), Songling virus (SGLV), and Yanggou tick virus (YGTV). PCR analysis detected DBTV exclusively in Hunchun ticks (minimum infection rates, MIR:4.73%) and YGTV in Antu specimens (MIR:0.97%). Conversely, SGLV was detected in ticks from all four regions, with MIR of 1.68% (Helong), 0.74% (Hunchun), 1.61% (Antu), and 4.79% (Longjing). Concurrently, SGLV was detected in 19 sheep blood samples from Longjing, yielding a positivity rate of 45.24%, while YGTV was identified in 13 cattle blood samples from Antu, with a positivity rate of 28.89%. Phylogenetically, the DBTV strain clustered with previously reported DBTV and Yongjia tick virus 1 isolates. Sheep-derived SGLV strains shared close evolutionary ties with tick-borne SGLV, whereas YGTV from cattle and ticks formed a distinct cluster with Russian strains but diverged into two branches from Chinese variants, suggesting evolutionary instability. CONCLUSION: These findings address critical knowledge gaps in the transmission dynamics and genetic diversity of emerging arboviruses while providing vital insights for developing cross-border surveillance strategies with significant public health implications.

Animals↗

PubMed2024

Identification of four TTN variants in three families with fetal akinesia deformation sequence.

BACKGROUND: TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants. METHODS: Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed. RESULTS: TTN c.38,876-2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases. CONCLUSIONS: Here we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.

Humans↗

PubMed2024

Comprehensive analysis of the expression, prognostic, and immune infiltration for COL4s in stomach adenocarcinoma.

BACKGROUND: Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. METHODS: The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. RESULTS: The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. CONCLUSION: COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.

Stomach Neoplasms↗