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Background Circulating tumour DNA (ctDNA) has emerged as a valuable liquid biopsy biomarker in the field of oncology, including head and neck squamous cell carcinomas (HNSCCs), offering potential insights into cancer diagnosis, progression, and prognosis. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in HNSCC. Methods PubMed and Ovid were searched as part of our review. Studies that investigated the relationship between ctDNA and prognosis in HNSCC patients were included. Outcomes extracted included basic characteristics, ctDNA details and survival data. Meta-analysis was performed on eligible studies to determine pooled progression-free/recurrence-free survival (RFS/PFS) and overall survival (OS). Results Twenty-two studies were included, involving 5062 HNSCC patients from 11 countries. The meta-analysis demonstrated that the positive ctDNA/methylation detection was associated with worse OS (HR = 2.00, 95% CI 1.35–2.96) and worse PFS/RFS (HR = 3.54, 95% CI 1.05–11.85). Positive ctEBV DNA was associated with poorer OS (HR = 2.86, 95% CI 1.84–4.45) and poorer PFS/RFS (HR = 1.93, 95% CI 1.74–2.13). Positive ctHPV DNA was associated with poorer OS (HR = 1.38, 95% CI 1.07–1.38) but not PFS/PFS (HR = 1.33, 95% CI 0.96–1.85). Conclusion Meta-analysis indicates that the status of ctDNA is significantly associated with the prognosis of HNSCC patients, with ctDNA/methylation-negative patients demonstrating better PFS/RFS and OS.

Rheumatoid arthritis (RA) is an autoimmune disease that can induce joint deformities and functional impairment, significantly impacting the overall well-being of individuals. Exosomes, which are cellularly secreted vesicles, possess favorable biological traits such as biocompatibility, stability, and minimal toxicity. Additionally, they contain nucleic acids, lipids, proteins, amino acids, and metabolites, serving as mediators in cellular communication and information exchange. Recent studies have demonstrated the association between exosomes and the pathogenesis of RA. Exosomes derived from mesenchymal stem cells, dendritic cells, and neutrophils exert influence on the biological functions of immune cells and joint cells, however, the precise mechanism remains largely unclarified. This comprehensive review systematically analyzes and summarizes the biological characteristics and functionalities of exosomes derived from diverse cellular sources, thus establishing a scientific foundation for the utilization of exosomes as diagnostic targets and therapeutic modalities in the context of RA.

Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARγ for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ; however, the molecular mechanisms by which PPARγ licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1-dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT that preserves white adipose tissue plasticity.

Droughts are recognized as one of the most devastating extreme climate events, leading to severe socioeconomic losses and ecological degradation globally under climate change. With global warming, the frequency and intensity of extreme droughts are increasing, posing critical challenges to water resource management. The Standardized Precipitation Conversion Index (SPCI) has demonstrated potential in drought monitoring; however, its applicability across diverse climatic zones and multiple temporal scales remains inadequately validated. This study addresses this gap by establishing a novel multi-scale inversion analysis using ERA5-based precipitable water vapor (PWV) and precipitation data. SPCI is selected for its advantage in eliminating climatic background biases through probability normalization, overcoming limitations of traditional indices such as the Standardized Precipitation Index (SPI) and Standardized Precipitation-Evapotranspiration Index (SPEI). We systematically evaluated the spatiotemporal evolution of Precipitation Efficiency (PE) and SPCI across four climatic zones in China. Results show that the first two principal components explain over 85% of the spatiotemporal variability of PE, with PC1 independently contributing from 82.05% to 83.80%. This high variance contribution underscores that the spatiotemporal patterns of PE are dominated by a few key climatic drivers, validating the robustness of the principal component analysis. SPCI exhibits strong correlation with SPI, exceeding 0.95 in the Tropical Monsoon Zone (TMZ) at scales of 1–6 months, indicating its utility for short-to-medium-term drought monitoring. Distinct zonal differentiation in PE patterns is revealed, such as the bimodal annual cycle in the Tropical-Subtropical Monsoon Composite Zone (TSMCZ). This study evaluates the performance of the SPCI against the widely used SPI and SPEI across four major climatic zones in China. It validates the SPCI’s applicability across China’s complex climates, providing a scientific basis for region-specific drought early warning and water resource optimization.

poisoning causes 90%-95% of global mushroom-related deaths, yet early prognostic biomarkers for poisoning are lacking. 33 patients with poisoning were recruited and categorized into survival and death group. Multivariate logistic regression analysis was used to investigate the independent mortality risk factors for poisoning patients. Untargeted serum metabolomics was performed to screen the differentially expressed metabolites. The quality control samples were used to evaluate the stability and reproducibility of ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analytical system. The prognosis predictive metabolic biomarkers were identified by ROC curve analysis. Correlations between metabolic biomarkers and biochemical indicators were analyzed by Spearman's correlation analysis. Significant differences were observed between the survival and death groups in clinical manifestations-such as gastrointestinal bleeding, dizziness, headache, delirious coma, infection, and shortness of breath-and in biochemical indicators, including alanine transaminase (ALT), aspartate transaminase (AST), prothrombin time and activated partial thromboplastin time (APTT). Metabolomic analysis identified 80 differentially expressed metabolites involved primarily in amino acid and unsaturated fatty acid metabolism. ROC analysis (AUC >0.9) screened nine potential metabolic biomarkers for predicting clinical outcomes: 9,10-Epoxyoctadecenoic acid, Phosphatidylinositol(16:0/18:2 (9Z,12Z)), N-Acetyl-L-aspartic acid, PI(20:3 (5Z,8Z,11Z)/18:0), Propionylcarnitine, Proline betaine, 4'-Methyl-(-)-epigallocatechin 3-(4-methyl-gallate), PG (18:1 (11Z)/22:6 (4Z,7Z,10Z,13Z,16Z,19Z)), and L-Proline. Notably, correlation analysis revealed that 9,10-Epoxyoctadecenoic acid was positively correlated with AST and activated partial thromboplastin time, whereas 4'-Methyl-(-)-epigallocatechin 3-(4-methyl-gallate), N-acetyl-L-aspartic acid, PI(16:0/18:2 (9Z,12Z)), PI(20:3 (5Z,8Z,11Z)/18:0), and Propionylcarnitine showed negative correlations with various liver and coagulation parameters. Serum metabolomics has identified metabolic biomarkers capable of predicting mortality in poisoning, with significant correlation to liver and coagulation injury. These biomarkers may facilitate early risk stratification and guide targeted therapeutic interventions. Limitations include small sample size and single-center retrospective design, which may restrict result generalizability.

Wnt/β-catenin signaling has been well established as a potent inhibitor of adipogenesis. Here, we identified a population of adipocytes that exhibit persistent activity of Wnt/β-catenin signaling, as revealed by the Tcf/Lef-GFP reporter allele, in embryonic and adult mouse fat depots, named as Wnt + adipocytes. We showed that this β-catenin-mediated signaling activation in these cells is Wnt ligand- and receptor-independent but relies on AKT/mTOR pathway and is essential for cell survival. Such adipocytes are distinct from classical ones in transcriptomic and genomic signatures and can be induced from various sources of mesenchymal stromal cells including human cells. Genetic lineage-tracing and targeted cell ablation studies revealed that these adipocytes convert into beige adipocytes directly and are also required for beige fat recruitment under thermal challenge, demonstrating both cell autonomous and non-cell autonomous roles in adaptive thermogenesis. Furthermore, mice bearing targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied such cells manifested enhanced glucose utilization. Our studies uncover a unique adipocyte population in regulating beiging in adipose tissues and systemic glucose homeostasis.

Background Cryptococcosis is progressively acknowledged among people, irrespective of the human with or without immunodeficiency virus (HIV). This change in epidemiology has been recorded in recent years, prompting closer examination and a broader understanding of the disease manifestations and risk factors. Methods The data of cryptococcal infections in China during 11 years were retrospectively analyzed. According to the position of infection, the patients were categorized into the pulmonary infection group and extrapulmonary infection group. The composition of the two groups was compared, and the potential risk factors of disseminated infection were analyzed. Logistic regression was used to analyze the prognostic risk factors of the disease. Results A total of 165 patients were enrolled. 113 (68.5%) were male, and the age was 47.49 (18–82) years. 101 cases (61.2%) had a normal immune function and 64 cases (38.8%) had impaired immune function. 45 patients had extrapulmonary infection, involving the central nervous system, bone and joint, skin and bloodstream, and 120 patients had simple pulmonary infection. The mortality of the extrapulmonary infection group (48.9%) was significantly higher than that of the pulmonary infection group (0.8%). According to univariate logistic regression analysis, immune status (hazard ratio [HR], 4.476; 95% confidence interval [CI], 1.725–11.618; P  = 0.002), infection position ([HR], 113.826; [CI], 14.607-886.967; P  < 0.001), white blood cell count, ([HR],1.209;[CI], 1.054–1.386; P  = 0.007), hemoglobin ([HR], 0.970; [CI], 0.955–0.986; P  < 0.001), platelet count ([HR], 0.993; [CI], 0.987–0.999; P  = 0.026), neutrophil percentage ([HR], 1.115; [CI], 1.065–1.168; P  < 0.001), lymphocyte percentage ([HR], 0.875; [CI], 0.827–0.927; P  < 0.001), neutrophil-to-lymphocyte Ratio (NLR) ([HR], 1.144; [CI], 1.072–1.221; P  < 0.001), monocyte percentage ([HR], 0.752; [CI], 0.618–0.915; P  = 0.004) were related to the prognosis. Multivariate logistic regression analysis showed that the infection position was remained related to the prognosis with statistical significance ([HR], 0.018; [CI], 0.001–0.384; P  = 0.001). Conclusion Extrapulmonary infection of Cryptococcosis is an important risk factor for prognosis. High levels of neutrophils and NLR, and low levels of lymphocytes and monocytes may lead to disseminated infection of Cryptococcosis. Further studies are needed to reduce the occurrence rate of extrapulmonary infection and mortality.

The mean survival of metastatic lung adenocarcinoma is less than 1 year, highlighting the urgent need to understand the mechanisms underlying its high mortality rate. The role of Extracellular vesicles (EVs) in facilitating the interactions between cancer cells and the metastatic microenvironment has garnered increasing attention. Previous studies on the role of EVs in metastasis have been primarily focused on cancer cell-derived EVs in modulating the functions of stromal cells. However, whether cancer stem cells (CSCs) can alter the metastatic properties of non-CSC cells, and whether EV crosstalk can mediate such interaction, have not been demonstrated prior to this report. In the present study, we integrated multi-omics sequencing and public database analysis with experimental validation to demonstrate, for the first time, the exosomal Mir100hg, derived from CSCs, could enhance the metastatic potential of non-CSCs both in vitro and in vivo. Mechanistically, HNRNPF and HNRNPA2B1 directly binds to Mir100hg, facilitating its trafficking via exosomes to non-CSCs. In non-CSCs, Mir100hg upregulates ALDOA expression, subsequently leading to elevated lactate production. Consequently, the increased lactate levels enhance H3K14 lactylation by 2.5-fold and promote the transcription of 169 metastasis-related genes. This cascade of events ultimately results in enhanced ALDOA-driven glycolysis and histone lactylation-mediated metastatic potential of non-CSC lung cancer cells. We have delineated a complex regulatory network utilized by CSCs to transfer their high metastatic activity to non-CSCs through exosomal Mir100hg, providing new mechanistic insights into the communication between these two heterogeneous tumor cell populations. These mechanistic insights provide novel therapeutic targets for metastatic lung cancer, including HNRNPF/HNRNPA2B1-mediated Mir100hg trafficking and the histone lactylation pathway, advancing our understanding of CSC-mediated metastasis while suggesting promising strategies for clinical intervention. Graphical Abstract

Riboswitches are non-coding RNA motifs that regulate gene expression in response to ligand binding. The glycine tandem riboswitch (GTR) contains two glycine aptamers that interact extensively, driving conformational changes in the downstream expression platform to control gene expression. Despite numerous studies, the role of glycine and RNA folding pathways in co-transcriptional regulation remains unclear. Here, we integrate single-molecule kinetic analysis, co-transcriptional RNA structure probing, and modeling to reveal that the GTR processes multiple molecular inputs sequentially, guided by polymerase pausing. Our findings elucidate its stepwise 5’-to-3’ folding pathway and demonstrate how sequential glycine binding to each aptamer, K + binding to a kink-turn, non-native folding intermediates, inter-aptamer docking driving binding site pre-organization, and modulation by transcription factor NusA collectively orchestrate co-transcriptional gene regulation. These results support a model wherein glycine binding cooperativity arises through non-equilibrium mechanisms, rather than a classical concerted model. Riboswitches are RNA elements that regulate gene expression through dynamic changes in secondary structure. Here, the authors reveal how the glycine tandem riboswitch integrates sequential signals via stepwise folding and binding of ligands to orchestrate gene regulation during transcription.

Objective To investigate the clinical factors related to poor prognosis of gallbladder cancer (GBC) patients, and to develop a prognostic model which may provide the guidance for clinical decision-making. Methods The clinical and pathological data of 136 patients with GBC admitted and treated in the Hunan Provincial People’s Hospital from January 2018 to July 2023 were retrospectively analyzed. All patients were followed up periodically by telephone, with the final follow-up on July 15, 2024. The Kaplan-Meier method was employed for univariate survival analysis. The log-rank test was utilized to assess differences in survival curves. A Cox regression model was applied for multivariate analysis to identify independent prognostic factors for GBC. Independent prognostic factors identified through Cox modeling were integrated into a nomogram. Finally, receiver operating characteristic (ROC) curves and calibration curves were plotted for 1-, 2-, and 3-year survival predictions. Results GBC patients were predominantly female and elderly. GBC patients with diabetes, jaundice and Child-Pugh B/C classification of liver function had poorer overall survival (OS) outcomes. Elevated serum tumor biomarkers CA19-9, CA125, CEA, CA724 and CYFRA21-1 were associated with unfavorable OS in GBC patients. Additionally, the differentiation grade, Lymphovascular invasion (LVI), perineural invasion (PNI), clinical staging and TNM staging were also related to the OS of GBC patients. For GBC patients who underwent surgical treatment, OS was significantly improved, with the most notable improvement observed in those who received radical surgery. GBC patients treated with chemotherapy-based drug treatment experienced an improvement in OS. Multivariate Cox regression analysis revealed that diabetes, elevated CA125, and advanced TNM stage were independent risk factors for GBC prognosis, while chemo-immunotherapy/targeted therapy was an independent protective factor. Conclusion Diabetes, elevated CA125 levels, TNM stage, and chemo-immunotherapy/targeted therapy are independent prognostic factors for GBC patients, which could be used to develop a nomogram model and contribute to provide the guidance for clinical treatment.