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关键词： AKI   IL-18   KIM-1   FGF-23   paracentesis  

摘要： Acute kidney injury (AKI) is a potentially fatal complication in patients with decompensated cirrhosis having therapeutic paracentesis, and early diagnosis is still difficult because of the low sensitivity of serum creatinine. We preemptively tested serum interleukin-18 (IL-18 kidney injury molecule-1 (KIM-1 and fibroblast growth factor-23 (FGF-23) in early prediction of post-paracentesis AKI in 80 hospitalized patients with tense ascites and normal baseline kidney function. Samples of blood were collected 2 h pre-paracentesis and 24 h post-paracentesis. Based on the Kidney Disease: Improving Global Outcomes definition, AKI, which happened within 72 h, was present in 40% of patients. Biomarkers levels at baseline were comparable. In 24 h of paracentesis, IL-18, KIM-1, and FGF-23 were high in patients who later developed AKI (all p value below .001) and had high-absolute changes than the non-AKI group. The largest discriminative performance was observed of FGF-23 (area under the curve 0.959 then IL-18 (0.931 and KIM-1 (0.903). In multivariate logistic regression controlling MELD-Na score, serum albumin, baseline eGFR and ascitic fluid volume, the post-paracentesis FGF-23 was still independently connected with AKI. Biomarkers of tubular injury, especially FGF-23, which increased shortly after the procedure were strongly correlated with future AKI and could increase risk stratification pending external validation.

关键词： NSCLC   IL-1 beta   chemotherapy   immunotherapy  

摘要： Interleukin (IL)-1 beta is known to promote lung cancer growth in both humans and mice. However, in the context of the current standard of care, which includes chemotherapy and immune checkpoint inhibitors, IL-1 beta can overcome resistance.

关键词： Spaceborne GNSS-R   TM-1 constellation   ocean wind speed retrieval   machine learning   multi-polarisation mode fusion  

摘要： Wind Speed (WS) is essential for air-sea interaction studies and weather monitoring. Spaceborne GNSS-R shows strong potential for WS retrieval, yet accuracy under high-wind conditions and environmental coupling remain challenging. This study employs China's multi-constellation GNSS-R mission Tianmu-1 (TM-1 integrating BDS, GPS, GLONASS, and Galileo observations. Bayesian-optimized machine learning models (CatBoost, LightGBM, and XGBoost) were developed by incorporating environmental variables, including significant wave height, sea surface temperature, and total precipitation. Three fusion strategies-multi-GNSS, multi-polarization, and pure data fusion-were evaluated over the Yellow and Bohai Seas. Results show that environmental integration reduces RMSE by 20 similar to 25% and increases correlation by 0.1 similar to 0.2. High-wind sample weighting effectively alleviates performance degradation under high conditions. LHCP observations from the C and E systems perform best, with accuracy ranked as C > E > G > R. Among fusion schemes, multi-polarization fusion achieves the highest accuracy (R = 0.88, RMSE = 1.685 m/s) and best spatial consistency. Overall, the proposed strategy significantly enhances the accuracy and robustness of GNSS-R WS retrieval and provides an effective framework for future multi-constellation missions and operational applications.

关键词： Stroke   type 2 diabetes mellitus   glucagon-like peptide 1 receptor agonists   cerebrovascular circulation   neuroprotection  

摘要： ObjectivesTo evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM and to outline their mechanisms of action in stroke prevention.MethodsA narrative review was conducted by synthesising data from cardiovascular outcome trials, meta-analyses and mechanistic studies involving GLP-1RAs such as semaglutide, liraglutide and dulaglutide. The search included literature on ischaemic stroke incidence, molecular pathways and clinical outcomes associated with GLP-1RA therapy.ResultsGLP-1RAs exhibit multiple protective mechanisms, including anti-inflammatory, antioxidant, neuroprotective and endothelial-stabilising effects. Long-acting agents demonstrate superior efficacy in reducing nonfatal and ischaemic stroke risk, with relative risk reductions ranging from 15% to 39% across major trials. These benefits are observed independent of glycemic control and appear most prominent in patients with preserved renal function and shorter diabetes duration. In contrast, short-acting exendin-based GLP-1RAs show limited cerebrovascular benefit. Treatment response may vary based on factors such as stroke subtype, baseline vascular risk and comorbidities.ConclusionGLP-1RAs offer significant promise as adjunctive pharmacotherapy for stroke prevention in individuals with T2DM. Their multifactorial benefits extend beyond glucose regulation and may influence clinical outcomes through systemic vascular and neuroprotective mechanisms. However, inconsistencies in trial outcomes and limited data in non-diabetic or high-risk populations underscore the need for targeted stroke-specific studies. Personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management.

关键词： Endothelin-1   carotid-femoral pulse wave velocity   aortic stiffness   chronic kidney disease  

摘要： Increased aortic stiffness (AS) is a recognized predictor of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD and endothelin-1 (ET-1 a potent vasoconstrictor, has been associated with vascular dysfunction and atherosclerosis. This study examined the relationship between serum ET-1 levels and AS in patients with non-dialysis CKD. A total of 232 adults with CKD stages 3-5 were enrolled. Fasting blood samples were obtained to measure serum ET-1 concentrations using an enzyme immunoassay, and AS was assessed by carotid-femoral pulse wave velocity (cfPWV) measured using cuff-based volumetric displacement, with cfPWV >10 m/s defining AS. Among the participants, 75 patients (32.3%) were classified as having AS. Compared with those without AS, patients with AS were older and had higher prevalences of diabetes mellitus and hypertension, as well as significantly higher serum ET-1 levels, blood pressure, fasting glucose, HbA1c, and urine protein-to-creatinine ratio. Serum ET-1 levels were positively correlated with cfPWV and remained independently associated with cfPWV in multivariable linear regression analysis. Furthermore, multivariable logistic regression identified serum ET-1, age, diastolic blood pressure, and diabetes mellitus as independent factors associated with AS, with consistent results observed in bootstrap analyses. These findings demonstrate an independent association between serum ET-1 levels and increased cfPWV and AS in patients with non-dialysis CKD.

关键词： HIV-1 gp120   lysosomal stress responses   reactive species interactome   reactive sulfur species   reactive nitrogen species   reactive oxygen species   reactive carbonyl species   TRPML1   redox sensor  

摘要： Background Increased lysosomal stress responses (LSR) are commonly implicated in the pathogenesis of neurodegenerative disorders including HIV-1-associated neurocognitive disorders (HAND). The HIV-1 envelope glycoprotein gp120 causes LSR, increases levels of ferrous iron (Fe2+) in the cytosol and in mitochondria, disrupts the reactive species interactome (RSI and increases neural cell death.Methods Using SH-SY5Y human neuroblastoma and U87MG human astrocytoma cells treated with gp120 and pharmacological modulators, we evaluated redox signaling and LSR by redox-sensitive fluorescent probes, spinning-disk confocal microscopy, flow cytometry, Western blotting, and immunostaining.Results Here, we report that TRPML1, an endolysosome redox-sensitive cation channel, is mechanistically involved in gp120-induced neurotoxicity. TRPML1 was activated by gp120-induced increases in cytosolic reactive oxygen species (ROS) and resulted in release of Fe2+ from endolysosomes in levels sufficient to increase cytosolic levels of Fe2+ and ROS as well as decrease levels of hydrogen sulfide (H2S). Reduced glutathione normally buffers intracellular Fe2+, but gp120 decreased endolysosome glutathione levels and disrupted this regulatory control mechanism thereby promoting TRPML1-mediated Fe2+ efflux from endolysosomes. TRPML1 redox activation led to changes to the RSI in endolysosomes including increased ROS, lipid peroxidation, nitric oxide, and sulfane sulfur as well as decreased H2S. These changes were accompanied by increased cysteine oxidation of luminal proteins and endolysosome deacidification. Pharmacological inhibition of TRPML1 or knocking down expression levels of TRPML prevented these effects.Conclusion Our findings suggest that TRPML1 redox activation controls gp120-induced endolysosome dysfunction and iron/redox imbalance, and further implicates TRPML1 in the pathogenesis of HAND.

关键词： Sepsis associated acute kidney injury   endothelial glycocalyx   renal resistive index   bedside doppler ultrasound   macro- microcirculatory dysfunction  

摘要： The interplay between macro-microcirculatory dysfunction and sepsis associated acute kidney injury (SA-AKI) remains elusive. This study aimed to explore the association between hemodynamics and endothelial damage in SA-AKI by evaluating the combined predictive value of renal resistive index (RRI) and plasma syndecan-1. This prospective observational study enrolled 80 septic patients admitted to the general intensive care unit (ICU) of a tertiary hospital from May to December 2024. Plasma syndecan-1 levels were measured at admission, and RRI was assessed within 24 h of ICU admission. Univariate and multivariate logistic regression models were applied to identify independent risk factors of SA-AKI. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis by calculating the area under the curve (AUC). Among 80 septic patients, 41(51.25%) developed AKI. Syndecan-1 levels were significantly higher in the AKI group [109.95 (73.67-221.40) vs.73.67 (54.59-109.95) ng/mL, p = 0.007 and RRI values were markedly elevated (0.69 +/- 0.08 vs. 0.60 +/- 0.06, p < 0.001) compared to non-AKI patients. Univariate analysis revealed syndecan-1 (OR = 2.68, 95%CI 1.29-5.59) and RRI (OR = 1.18, 95%CI 1.09-1.28) as predictors of AKI. In multivariate models adjusted for confounders, both plasma syndecan-1 (OR = 3.57, 95%CI 1.01-12.64, p = 0.048) and RRI (OR = 1.19, 95% CI 1.07-1.33, p = 0.002) retained significance. A predictive model using a combination of plasma syndecan-1 and RRI achieved superior diagnostic performance (AUC 0.859, sensitivity 87.8%, specificity 92.3%). In patients with SA-AKI, elevated plasma syndecan-1 and RRI were identified as independent risk factors. The combination of syndecan-1 and RRI can serve as synergistic biomarkers for the prediction of SA-AKI.