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351 result(s) for "Zhao, Shuqi"
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Blood biomarkers are altered in elderly hematological patients exhibiting a mosaic loss of the Y chromosome in bone marrow cells
Background Mosaic loss of the Y chromosome (LOY) is a frequent somatic alteration observed in aging males, linked to clonal hematopoiesis and elevated risks of hematologic malignancies. However, the direct physiological implications of LOY in elderly patients with hematologic disorders remain unclear. We investigated blood biomarker changes associated with LOY in elderly male patients with hematologic malignancies. Methods We retrospectively analyzed 196 elderly male patients (median age, 71 years) with LOY detected via bone marrow karyotyping (2017–2022). Participants were stratified into four groups: no disease ( n  = 22); acute myelogenous leukemia, myelodysplastic syndrome (including refractory anemia [RA], refractory anemia with excess blasts [RAEB], and RAEB in transformation [RAEB-T]), chronic myelomonocytic leukemia (CMML) (AML/MDS group, n  = 52); multiple myeloma (MM, n  = 37); and chronic lymphocytic leukemia (CLL), Hodgkin’s lymphoma (HL), and non-Hodgkin’s lymphoma (NHL) (CLL/lymphoma group, n  = 85). Controls ( n  = 120) exhibited normal 46,XY karyotypes. Blood markers ( n  = 22)—including blood cell counts, cytokines, immunoglobulins, and thyroid hormones—were assessed using non-parametric tests and multivariate regression analysis. Results LOY was detected in 4% of patients (3% pure LOY, 1% LOY with additional abnormalities). AML/MDS patients with LOY were younger (median 68.5 vs. 75.5 years in no-disease, p  = 0.004) and exhibited higher LOY burden (60% vs. 33% in CLL/lymphoma, p  < 0.001). Multivariate analysis revealed age as an independent risk factor for AML/MDS ( p  = 0.002), while LOY burden specifically correlated with CLL/lymphoma ( p  = 0.012). Distinct biomarker profiles emerged: LOY-positive AML/MDS patients showed reduced hemoglobin, platelets, and cytokines (e.g., reduced interleukin-2, interferon-gamma) versus controls ( p  < 0.05), whereas CLL/lymphoma cases correlated with decreased immunoglobulins (IgM) and cytokines (e.g., interleukin-4, interleukin-17 A). Notably, individuals without hematologic disease exhibited stable biomarker profiles irrespective of LOY status, suggesting context-dependent effects of LOY. A high LOY burden (≥ 75%) was associated with cytopenias in AML/MDS, characterized by decreased white blood cell (WBC) count, neutrophil count (NEC), and platelet (PLT) count ( p  < 0.05). Conclusion LOY exhibits disease-specific associations with immune-metabolic dysregulation, particularly in AML/MDS and CLL/lymphoma. Its varying burden and biomarker profiles suggest potential utility in risk stratification, warranting further prospective validation.
Recent progress in terahertz modulation using photonic structures based on two‐dimensional materials
Terahertz (THz) technology has attracted great attention in the past few decades for its unique applications in various fields, including spectroscopy, noninvasive detection, wireless communications, and imaging. In parallel to this, the practical, fast, and broadband modulation of THz waves is becoming indispensable. Two‐dimensional (2D) materials exhibit unusual optical and electrical properties, which has prompted tremendous interest and significant advances in THz modulation. This review provides the recent progress in 2D materials‐based THz modulators, outlining the operating principles, including all‐optical, electro‐optic, magneto‐optic, and other exotic mechanisms. We focus on the recent advances in THz modulation by the designed photonic structures, such as heterostructure, metamaterial, capacitor, optical cavity, and waveguide integration. Lastly, we discussed the challenges and opportunities for 2D materials‐based THz modulators and presented our prospects for the future development. Two‐dimensional (2D) materials‐based terahertz (THz) modulators are attracting increased attention because they play important roles in THz communication, sensing, and biomedical diagnostics. This review summarizes the recent progress of 2D materials for THz modulation with different operation principles and photonic structures. The challenges and prospects for 2D‐materials‐based THz modulators are also proposed to further push forward the development of THz modulation.
Identification of favorable SNP alleles and candidate genes for traits related to early maturity via GWAS in upland cotton
Background Early maturity is one of the most important and complex agronomic traits in upland cotton ( Gossypium hirsutum L). To dissect the genetic architecture of this agronomically important trait, a population consisting of 355 upland cotton germplasm accessions was genotyped using the specific-locus amplified fragment sequencing (SLAF-seq) approach, of which a subset of 185 lines representative of the diversity among the accessions was phenotypically characterized for six early maturity traits in four environments. A genome-wide association study (GWAS) was conducted using the generalized linear model (GLM) and mixed linear model (MLM). Results A total of 81,675 SNPs in 355 upland cotton accessions were discovered using SLAF-seq and were subsequently used in GWAS. Thirteen significant associations between eight SNP loci and five early maturity traits were successfully identified using the GLM and MLM; two of the 13 associations were common between the models. By computing phenotypic effect values for the associations detected at each locus, 11 highly favorable SNP alleles were identified for five early maturity traits. Moreover, dosage pyramiding effects of the highly favorable SNP alleles and significant linear correlations between the numbers of highly favorable alleles and the phenotypic values of the target traits were identified. Most importantly, a major locus ( rs13562854 ) on chromosome D t 3 and a potential candidate gene ( CotAD_01947 ) for early maturity were detected. Conclusions This study identified highly favorable SNP alleles and candidate genes associated with early maturity traits in upland cotton. The results demonstrate that GWAS is a powerful tool for dissecting complex traits and identifying candidate genes. The highly favorable SNP alleles and candidate genes for early maturity traits identified in this study should be show high potential for improvement of early maturity in future cotton breeding programs.
ALDH1L1 reverses CD8+ T cell exhaustion in the oral squamous cell carcinoma microenvironment by reprogramming L-glutamate metabolism
Background Oral squamous cell carcinoma (OSCC) induces CD8⁺ T-cell exhaustion within the tumor microenvironment (TME) through metabolic reprogramming, contributing to the limited efficacy of immunotherapy. Targeting tumor metabolism is a pivotal strategy. Whether Aldehyde dehydrogenase 1 family member L1 (ALDH1L1), a key enzyme in folate metabolism, can modulate the function of CD8⁺ T cell to enhance immunotherapy efficacy remains unclear. This research aims to elucidate the specific mechanism by which ALDH1L1 regulates metabolic reprogramming in OSCC and influences CD8⁺ T-cell immunotherapy. Methods The impact of ALDH1L1 on CD8⁺ T cell was assessed using patient samples, engineered OSCC cell lines, and C3H mouse models. Integrated transcriptomics and metabolomics revealed its role in L-glutamate metabolism, further investigated via molecular docking and co-immunoprecipitation. In vitro, the direct effect of L-glutamate on CD8⁺ T-cell exhaustion was probed via transcriptomic sequencing, mitochondrial functional assays, and immunofluorescence. An ALDH1L1-targeting compound from virtual screening was evaluated in vivo to enhance anti-PD-1 therapy. Results Low expression of ALDH1L1 in OSCC correlates with decreased CD8⁺ T-cell infiltration and increased exhaustion. In vivo and in vitro models demonstrated that ALDH1L1 regulates IL-15 expression to influence CD8⁺ T-cell proliferation. Multi-omics analysis revealed that ALDH1L1 downregulation enriched the L-glutamate metabolic pathway. Mechanistically, ALDH1L1 directly interacts with GLUL, leading to L-glutamate accumulation in the TME. Subsequent analyses demonstrated that L-glutamate suppresses the PI3K/Akt/FoxO1 signaling axis in CD8⁺ T cell, impairing mitochondrial function and inhibiting oxidative phosphorylation (OXPHOS). Stevioside, identified as an ALDH1L1-targeting compound, significantly enhanced the efficacy of anti-PD-1 therapy, leading to reduced tumor growth in mouse models. Conclusions Downregulation of ALDH1L1 in OSCC drives CD8⁺ T-cell exhaustion via a GLUL-mediated increase in L-glutamate, which suppresses mitochondrial OXPHOS. Pharmacological modulation of ALDH1L1 with stevioside represents a promising strategy to enhance anti-PD-1 immunotherapy efficacy, providing a novel combination therapeutic strategy for OSCC.
iTRAQ-Based Proteomics Reveals the Potential Mechanisms Underlying Diet Supplementation with Stevia Isochlorogenic Acid That Alleviates Immunosuppression in Cyclophosphamide-Treated Broilers
The extensive use of antibiotics in intensive farming weakens immunity and threatens food safety. Stevia isochlorogenic acid (SICA), a kind of dicaffeoylquinic acid derived from stevia residue, exhibits strong antioxidant activity. This study evaluated the ability of SICA to improve immune function in an immunosuppressed broiler model. SICA significantly increased the spleen, thymus, and bursa of Fabricius indices (p < 0.05), alleviated spleen damage, and elevated serum interleukin-2 (IL-2), IL-4, interferon-γ, IL-1β, tumor necrosis factor-α, immunoglobulins (IgA, IgM, IgG), and complement components C3 and C4 (p < 0.05). Isobaric tags for relative and absolute quantification-based proteomics indicated that SICA enhanced splenic immune function by activating cell adhesion molecules, phagosomes, and the intestinal immune network for IgA production pathways. Quantitative PCR analysis showed upregulation of mRNA and protein levels of B-cell receptor, major histocompatibility complex class II, protein tyrosine phosphatase receptor type C, and neutrophil cytosolic factor 2 (p67phox) and downregulation of C-C motif chemokine receptor 9. Molecular docking demonstrated the strongest binding affinity between SICA and p67phox. Overall, SICA effectively alleviated immunosuppression in broiler chickens and represents a promising natural alternative to antibiotic feed additives.
Viral Infection Induces Expression of Novel Phased MicroRNAs from Conserved Cellular MicroRNA Precursors
RNA silencing, mediated by small RNAs including microRNAs (miRNAs) and small interfering RNAs (siRNAs), is a potent antiviral or antibacterial mechanism, besides regulating normal cellular gene expression critical for development and physiology. To gain insights into host small RNA metabolism under infections by different viruses, we used Solexa/Illumina deep sequencing to characterize the small RNA profiles of rice plants infected by two distinct viruses, Rice dwarf virus (RDV, dsRNA virus) and Rice stripe virus (RSV, a negative sense and ambisense RNA virus), respectively, as compared with those from non-infected plants. Our analyses showed that RSV infection enhanced the accumulation of some rice miRNA*s, but not their corresponding miRNAs, as well as accumulation of phased siRNAs from a particular precursor. Furthermore, RSV infection also induced the expression of novel miRNAs in a phased pattern from several conserved miRNA precursors. In comparison, no such changes in host small RNA expression was observed in RDV-infected rice plants. Significantly RSV infection elevated the expression levels of selective OsDCLs and OsAGOs, whereas RDV infection only affected the expression of certain OsRDRs. Our results provide a comparative analysis, via deep sequencing, of changes in the small RNA profiles and in the genes of RNA silencing machinery induced by different viruses in a natural and economically important crop host plant. They uncover new mechanisms and complexity of virus-host interactions that may have important implications for further studies on the evolution of cellular small RNA biogenesis that impact pathogen infection, pathogenesis, as well as organismal development.
Genome-wide identification and mining elite allele variation of the Monoacylglycerol lipase (MAGL) gene family in upland cotton (Gossypium hirsutum L.)
Background Monoacylglycerol lipase ( MAGL ) genes belong to the alpha/beta hydrolase superfamily, catalyze the terminal step of triglyceride (TAG) hydrolysis, converting monoacylglycerol (MAG) into free fatty acids and glycerol. Results In this study, 30 MAGL genes in upland cotton have been identified, which have been classified into eight subgroups. The duplication of GhMAGL genes in upland cotton was predominantly influenced by segmental duplication events, as revealed through synteny analysis. Furthermore, all GhMAGL genes were found to contain light-responsive elements. Through comprehensive association and haplotype analyses using resequencing data from 355 cotton accessions, GhMAGL3 and GhMAGL6 were detected as key genes related to lipid hydrolysis processes, suggesting a negative regulatory effect. Conclusions In summary, MAGL has never been studied in upland cotton previously. This study provides the genetic mechanism foundation for the discover of new genes involved in lipid metabolism to improve cottonseed oil content, which will provide a strategic avenue for marker-assisted breeding aimed at incorporating desirable traits into cultivated cotton varieties.
Association of GhGeBP genes with fiber quality and early maturity related traits in upland cotton
Transcription Factors (TFs) are key regulators of how plants grow and develop. Among the diverse TF families, the Glabrous-enhancer binding protein (GeBP) family plays a key role in trichome initiation and leaf development. The specific roles of GeBP TFs in plants remain largely unexplored, although GeBP transcription factors play important roles in plants. This study identified 16 GhGeBP genes in Gossypium hirsutum , ranging from 534 bp ( GhGeBP14 ) to 1560 bp ( GhGeBP2 ). Phylogenetic analysis grouped 16 GhGeBP genes clustered into three subgroups, unevenly distributed across 14 chromosomes. Analysis of the cis -acting elements revealed 408 motifs in the 2 kb upstream regions of the promoters, including stress-responsive, phytohormone-responsive, and light-responsive elements. Tissue-specific expression analysis showed 8 GhGeBP genes were highly expressed across all tissues, while GhGeBP4 and GhGeBP12 were down-regulated under conditions of drought, salt, cold, and heat stress. A genome-wide association study (GWAS) identified GhGeBP4 was associated with fiber micronaire (FM) and fiber strength (FS), while GhGeBP9 was linked to the node of the first fruiting branch (NFFB) and flowering time (FT). Haplotype analysis revealed that GhGeBP4 -HAP2 exhibited higher fiber quality traits, while GhGeBP9 -HAP2 was associated with early maturity. The results of this study offer significant insights that are worthy of further investigation into the role of the GhGeBP gene family in G. hirsutum and promising targets for marker-assisted selection strategies in cotton breeding programs, particularly for improving fiber quality and early maturity traits.
Clinical features and prognosis of patients with myeloid neoplasms harboring t(7;11)(p15;p15) translocation: a single-center retrospective study
Background For myeloid neoplasms with t(7;11)(p15;p15) translocation, the prognosis is quite dismal. Because these tumors are rare, most occurrences are reported as single cases. Clinical results and optimal treatment approaches remain elusive. This study endeavors to elucidate the clinical implications and prognosis of this cytogenetic aberration. Methods This study retrospectively analyzed 23 cases of myeloid neoplasm with t(7;11)(p15;p15). Clinicopathological characteristics, genetic alterations, and outcomes were evaluated, and the Kaplan-Meier method was employed to construct survival curves. Results Of these, nine cases were newly diagnosed acute myeloid leukemia (ND AML), seven presented with relapsed refractory AML (R/R AML), four had myelodysplastic syndrome (MDS), two had secondary AML, and one exhibited a mixed germinoma associated with MDS. Patients with t(7;11)(p15;p15) in AML were primarily younger females who preferred subtype M2. Interestingly, these patients had decreased hemoglobin and red blood cell counts, along with markedly elevated levels of lactic dehydrogenase and interleukin-6, and exhibited the expression of CD117. R/R AML patients exhibited a higher likelihood of additional chromosome abnormalities (ACAs) besides t(7;11). WT1 and FLT3 -ITD were the most commonly found mutated genes, and 10 of those instances showed evidence of the NUP98::HOXA9 fusion gene. The composite complete remission rate was 66.7% (12/18), while the cumulative graft survival rate was 100% (4/4). However, the survival outcomes were dismal. Interestingly, the median overall survival for R/R AML patients was 4.0 months (95% CI: 1.7–6.4). Additionally, the type of AML diagnosis or the presence of ACAs or molecular prognostic stratification did not significantly influence clinical outcomes ( p  = 0.066, p  = 0.585, p  = 0.570, respectively). Conclusion Myeloid leukemia with t(7;11) exhibits unique clinical features, cytogenetic properties, and molecular genetic characteristics. These survival outcomes were dismal. R/R AML patients have a limited lifespan. For myeloid patients with t(7;11), targeted therapy or transplantation may be an effective course of treatment.
Metabolomic and Transcriptomic Analyses of Soft-Body Coloration in Jinjiang Oyster (Crassostrea ariakensis)
The coloration of shellfish significantly influences both environmental adaptability and economic value. In the Jinjiang oyster (Crassostrea ariakensis), soft-body color varies between individuals, with an orange-yellow phenotype distinct from the milky white coloration of the wild type. To elucidate the compositional differences and molecular mechanisms underlying orange-yellow (designated as CaR) versus milky white (CaW) soft-body color in C. ariakensis, we conducted comparative ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) non-targeted and transcriptomic analyses. A total of 280 differential accumulation metabolites (DAMs) and 691 differentially expressed genes (DEGs) were detected between the CaR and CaW groups. The metabolite set enrichment analysis (MSEA) revealed that DAMs were significantly enriched in pigment metabolism pathways, including tyrosine metabolism, porphyrin metabolism, and lipid metabolism. Furthermore, genes associated with melanin synthesis and carotenoids conversions or transports were upregulated in the CaR vs. CaW group. These genes included Cyp4z1, Cyp4f22, Cyp17a1, Cyp1a5, Cyp2d28a, Lrp4, Aldh, and Tyr-3, potentially driving the accumulation of pheomelanin and carotenoids. This study demonstrates the vital roles of melanin and carotenoid metabolism in Jinjiang oyster body color formation, providing key insights into the molecular mechanisms of color determination in shellfish.