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Peng Zhao

Publications and source records attributed to Peng Zhao.

9 recordsLinked to original sources
PubMed2026

Spatiotemporal mapping of tertiary lymphoid structure heterogeneity shapes immune niches and clinical outcomes in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy with limited therapeutic options. The spatial architecture and functional diversity of tertiary lymphoid structures (TLSs) in iCCA remain unclear. Here, we present a multimodal spatial atlas of TLSs and identified intratumoral TLSs (iTLSs) as independent prognostic markers. Bulk proteomic profiling of 214 discovery and 155 validation cases identified a four-tier TLS-based tumor microenvironment classification system and supported development of a TLS-predictive random forest classifier. Imaging mass cytometry revealed that iTLS+ tumors harbor structured immune architectures, where M1-like tissue-resident macrophages (RTMs), dendritic cells, and CXCL13+ CD4+ T cells colocalize to form antigen-presenting neighborhoods (apc-CNs) spatially coupled to TLS core regions (TLScore-CNs). Single-cell spatial transcriptomics further resolved 61 TLSs into 14 spatial niches and defined a pseudotemporal maturation continuum: aggregated, activated, and postactivated. Intraniche communication, primarily mediated by ifnCAFs, iCAFs, and CXCL12+ macrophages, evolved dynamically with maturation. Single-nucleus RNA sequencing combined with Tangram-based spatial mapping revealed CXCL12+ macrophages and iCAFs forming a peripheral band in aggregated TLSs, whereas ifnCAFs infiltrated TLS interiors during activation. These findings define TLS heterogeneity and provide insights for stroma-directed immunotherapy.

Cholangiocarcinoma↗
PubMed2026

Type IV-C CRISPR-Cas effector complexes recognize double-stranded DNA and switch on collateral cleavage of ssDNA and RNA.

Type IV-C CRISPR-Cas systems remain enigmatic compared to other class 1 systems. Here, we expand the type IV-C catalog, identifying two phylogenetically distinct clades primarily found in archaea (IV-C1) or bacteria (IV-C2), distinguishable by the Cas10IVc subunit architecture. We functionally and structurally characterize type IV-C1 systems from Thermococcus onnurineus (Ton) and Pyrococcus abyssi (Pab). Type IV-C complexes assemble with crRNAs derived from distinct CRISPR arrays and recognize a 5'-GGG-3' protospacer adjacent motif (PAM) to bind double-stranded DNA targets. Target recognition activates the HD domain of Cas10IVc, triggering metal-dependent collateral cleavage of single-stranded DNA and RNA. This behavior is explained by allosteric alignment of the HD active site, triggered by PAM-dependent R-loop formation, as revealed by cryo-EM. Together, our findings suggest that type IV-C systems provide immunity via non-specific cleavage of nucleic acids generated during mobile genetic element replication or transcription.

CP: molecular biology↗
PubMed2026

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50 μM, and intracellular concentrations and cell viability were monitored over 48 h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry↗
PubMed2025

Integrative omics of the genetic basis for wheat WUE and drought resilience reveal the function of TaMYB7-A1.

Improving wheat drought resilience and water use efficiency (WUE) is critical for sustaining productivity under increasing water scarcity. Here, we integrate genome-wide association study (GWAS), expression quantitative trait locus (eQTL) mapping, population-transcriptome analysis, and summary-data-based mendelian randomization (SMR), followed by functional validation using indexed EMS mutants and transgenic lines, to systematically identify key WUE regulators. GWAS across water conditions in 228 accessions identifies 73 quantitative trait loci (QTLs) for WUE-traits. Transcriptome profiling of 110 diverse accessions reveals 28 drought-responsive modules. eQTL mapping uncovers 146,966 regulatory variants, including condition-specific hotspots associated with key drought-related pathways. Integrative analysis underscores 85 high-confidence candidate genes, notably TaMYB7-A1. Overexpression of TaMYB7-A1 enhances photosynthesis, WUE, root development, and grain yield under drought condition by activating TaPIP2;2-B1 (water transport), TaRD20-D1 (stomatal regulation), and TaABCB4-B1 (root growth), reflecting reduced water loss and improved physiological resilience. Our study presents a comprehensive regulatory map and robust targets for wheat drought adaptation and resilient cultivar breeding.

Triticum↗
PubMed2025

Dissecting the shared genetic architecture of schizophrenia with ventricular subregion volumes.

Schizophrenia is characterized by cerebral ventricular enlargement as an early and consistent structural anomaly. While genetic factors significantly influence both schizophrenia and cerebral ventricular enlargement, the shared genetic etiology between them requires further investigation. Using summary statistics from recent large genome-wide association studies on schizophrenia and 9 ventricular subregion volumes phenotypes. Gaussian causal mixture modeling was applied to characterize the genetic architecture and overlap between schizophrenia and ventricular subregion volumes phenotypes. Local genetic correlation was investigated with Local Analysis of Variant Association. The conjunctional false discovery rate framework was used to identify the specific shared genetic loci, annotated with FUMA. Gaussian causal mixture modeling estimated schizophrenia to be more polygenic more polygenic (9574 trait-influencing variants) than ventricular subregion volumes phenotypes (157-1267 trait-influencing variants). Conjunctional false discovery rate analysis identified 42 shared genetic loci, 17 loci were identified as novel for both schizophrenia and the ventricular subregion volumes phenotypes. Local Analysis of Variant Association revealed that 11 distinct loci demonstrated significant differences, among which 4 loci were situated in the Major Histocompatibility Complex region. Annotated genes in shared loci were enriched in molecular signaling pathways involved in inflammation and the brain structure. The shared loci between them were annotated and enriched in Major Histocompatibility Complex and inflammation-related pathways, highlighting new opportunities for future investigation.

Schizophrenia↗
PubMed2025

Transcriptomics and proteomics reveal associations between myometrium and intrauterine adhesions.

BACKGROUND: Intrauterine adhesions (IUAs) is a gynecological condition with a poor therapeutic prognosis, that severely threatens the fertility and the reproductive physiology and psychological health of women. Our previous research on the use of umbilical cord mesenchymal stem cells (HUCMSCs) for treating IUAs revealed that CM-Dil-labelled HUCMSCs were barely distributed in the endometrial epithelium. Instead, these cells were predominantly found in the myometrium, with no statistically significant difference in distribution compared to the endometrial stromal cells. Therefore, we aimed to explore the associations between the myometrium and IUAs. METHODS: Eight patients with moderate and 5 severe lesional IUAs were included in the experimental group. The control group included 7 patients whose inner and outer myometrium were normal. We used H&E, Masson's trichrome and immunohistochemical staining to obtain the pathological features of the tissues. Transcriptomic and proteomic analyses were conducted to identify differentially expressed genes, proteins and enrichment pathways. RESULTS: Both IUAs lesion tissues expressed the smooth muscle markers &#x3b1;-SMA and H-caldesmon, and there was no significant difference between severe IUAs tissue and normal myometrium (p&#x2009;>&#x2009;0.05). Transcriptomic and proteomic data revealed that genes and proteins involved in cell mitosis, such as KIF14, KIF4A, and CIT, were downregulated in both IUAs lesion tissues compared with the inner myometrium (p&#x2009;<&#x2009;0.05). Additionally, some genes or proteins that participate in activating the complement-coagulation cascade system and extracellular matrix (ECM) degradation also significantly differed (p&#x2009;<&#x2009;0.05). CONCLUSIONS: Transcriptomic and proteomic data revealed a correlation between endometrial injury and the myometrium. These findings preliminarily revealed that the myometrium possibly contributes to the aetiology and progression of IUAs through dual mechanisms. On the one hand, the myometrium inhibits endometrial regeneration by suppressing the cell mitogenic pathway. On the other hand, it promotes fibrosis by activating the complement-coagulation cascade system and inhibiting the ECM degradation pathway. These new findings increase our understanding of the pathogenesis of IUAs and potentially contribute to the application of precision clinical treatment for IUAs.

Humans↗
PubMed2025

Avian Migration-Mediated Transmission and Recombination Driving the Diversity of Gammacoronaviruses and Deltacoronaviruses.

In the wake of pandemics like COVID-19, which have zoonotic origins, the role of wildlife as reservoirs for emerging infectious diseases has garnered heightened attention. Migratory birds, traversing continents, represent a potent but under-researched vector for the spread of infectious diseases, including novel coronaviruses. This study delves into the genetic diversity and transmission dynamics of coronaviruses in migratory birds, presenting pivotal findings. From April 2019 to April 2023, we screened 5,263 migratory bird samples collected from Shanghai, China, identifying 372 coronavirus-positive samples belonging to five avian-related coronavirus subgenera and subsequently obtaining 120 complete genome sequences. To facilitate further research with a global perspective, the study curated all available 19,000 avian-associated coronaviruses and expanded the original 12 species to 16, including three novel coronavirus species identified in our study and one re-classified species from the public domain. The study illuminates the intricate genetic evolution and transmission dynamics of birds-related coronaviruses on a global scale. A notable aspect of our research is the identification of complex recombination patterns within the spike protein across different virus species and subgenera, highlighting migratory birds as a reservoir of coronavirus. Notably, the coronaviruses found in migratory birds, predominantly from the orders Anseriformes, Charadriiformes, and Pelecaniformes, with domestic ducks from Anseriformes playing a key role in bridging the transmission of coronaviruses between migratory and non-migratory birds. These findings reveal the genetic and recombination characteristics of coronaviruses in migratory birds, emphasizing the critical role of ecologically pivotal bird species in coronavirus transmission and genetic diversity shaping.

Animals↗
PubMed2025

Integrated multi-omics analyses provide new insights into genomic variation landscape and regulatory network candidate genes associated with walnut endocarp.

Persian walnut (Juglans regia) is an economically important nut oil tree; the fruit has a hard endocarp/shell to protect seeds, thus playing a key role in its evolution, and the shell thickness is an important trait for walnut breeding. However, the genomic landscape and the gene regulatory networks associated with walnut shell development remain to be systematically elucidated. Here, we report a high-quality genome assembly of the walnut cultivar 'Xiangling' and construct a graphic structure pan-genome of eight Juglans species to reveal the genetic variations at the genome level. We re-sequence 285 accessions to characterize the genomic variation landscape. Through genome-wide association studies (GWAS), we identified 19 loci associated with more than 268 loci that underwent selection during walnut domestication and improvement. Multi-omics analyses, including transcriptomics, metabolomics, DNA methylation, and spatial transcriptomics across eleven developmental stages, revealed several candidate genes related to secondary cell biosynthesis and lignin accumulation. This integrated multi-omics approach revealed several candidate genes associated with secondary cell biosynthesis and lignin accumulation, such as UGP, MYB308, MYB83, NAC043, NAC073, CCoAOMT1, CCoAOMT7, CHS2, CESA7, LAC7, COBL4, and IRX12. Overexpression of JrUGP and JrMYB308 in Arabidopsis thaliana confirmed their roles in lignin biosynthesis and cell wall thickening. Consequently, our comprehensive multi-omics findings offer novel insights into walnut genetic variation and network regulation of endocarp development and shell thickness, which enable further genome-informed breeding strategies for walnut cultivar improvement.

Juglans↗