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Synthetic antidiabetic drugs are often associated with various adverse side effects, including hypoglycemia, nausea, gastrointestinal disturbances, headaches, and even liver damage. In contrast, plant-derived natural antidiabetic bioactive compounds typically exhibit lower toxicity and fewer side effects and have been reported to aid effectively in diabetes management. These plant extracts regulate diabetes by restoring pancreatic function, enhancing insulin secretion, inhibiting intestinal glucose absorption, and facilitating insulin dependent metabolism. This study explored four extraction methods, including reflux distillation (RD), ultrasound assisted extraction (UAE), microwave assisted extraction (MAE), and enzyme assisted extraction (EAE) to optimize the yield of crude leaf extract and vasicine from Adhatoda zeylanica. RD produced the highest crude extract yield (98.29 g/kg of dried leaf), while MAE was the most effective for vasicine extraction, yielding 2.44 g vasicine per kg dried leaf. High Performance Liquid Chromatography (HPLC) with a diode array detector (DAD) was used to identify and quantify vasicine, a quinazoline alkaloid with known antidiabetic properties. The hypoglycemic effects of leaf extracts were evaluated in alloxan-induced diabetic mice, and the effect of A. zeylanica extract was compared to the extracts of Centella asiatica, Allamanda cathartica, and the standard drug metformin. At a dose of 400 mg/kg body weight (BW), methanolic leaf extracts of A. zeylanica, C. asiatica, and A. cathartica reduced blood glucose level by 78.95 %, 74.50 %, and 70.19 %, respectively, compared to the standard drug metformin, which reduced blood glucose levels by 85.84 %. A. zeylanica at 400 mg/kg BW dose and metformin demonstrated statistically similar and significant blood glucose level reduction (p < 0.001). Additionally, therapeutic doses of A. zeylanica leaf extract exhibited low cytotoxicity (cell survival rate >89 %), highlighting its potential as a safe and effective source of antidiabetic agent.

Objective: Gliomas are the most common intracranial tumors with the highest degree of malignancy. Disturbed cholesterol metabolism is one of the key features of many malignant tumors, including gliomas. This study aimed to investigate the significance of cholesterol metabolism-related genes in prognostic prediction and in guiding individualized treatment of patients with gliomas.

Methods: Transcriptional data and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Intraoperative glioma samples retained in our unit and the corresponding clinicopathological information were also collected with the patients' knowledge. Firstly, cholesterol metabolism-related gene signatures (CMRGS) were identified and constructed based on difference analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and univariate/multivariate COX analysis. Then, the role of CMRGS in predicting the prognosis of gliomas and distinguishing immune landscapes was evaluated by using nomograms, survival analysis, enrichment analysis, and immune-infiltration analysis. Finally, the drug sensitivity of gliomas in different risk groups was evaluated using the oncoPredict algorithm, and potentially sensitive chemotherapeutic and molecular-targeted drugs were identified.

Results: The prognostic CMRGS contained seven genes: APOE, SCD, CXCL16, FABP5, S100A11, TNFRSF12A, and ELOVL2. Patients were divided into high- and low-risk groups based on the median cholesterol metabolic index (CMI). There were significant differences in clinicopathological characteristics and overall survival between groups. COX analysis suggested that CMRGS was an independent risk factor for glioma prognosis and had a better predictive performance than several classical indicators. In addition, GSEA, immune infiltration analysis showed that CMRGS could differentiate the immune landscapes of patients in groups. The reliability of CMRGS was validated in the CGGA cohort and our Gusu cohort. Finally, 14 drugs sensitive to high-risk patients and 16 drugs sensitive to low-risk patients were identified.

Conclusion: The CMRGS reliably predicts glioma prognosis in multiple cohorts and may be useful in guiding individualized treatment.

Statins are widely used for treating lipid disorders and cardiovascular diseases. However, the therapeutic efficiency and adverse effects of statins vary among different patients, which numerous clinical and epidemiological studies have attributed to genetic polymorphisms in statin-metabolizing enzymes and transport proteins. The metabolic processes of statins are relatively complex, involving spontaneous or enzyme-catalyzed interconversion between more toxic lactone metabolites and active acid forms in the liver and bloodstream, influenced by multiple factors, including the expression levels of many metabolic enzymes and transporters. Addressing the variable statin therapeutic outcomes is a pressing clinical challenge. Transcription factors and epigenetic modifications regulate the metabolic enzymes and transporters involved in statin metabolism and disposition and, therefore, hold promise as 'personalized' targets for achieving optimized statin therapy. In this review, we explore the potential for customizing therapy by targeting the metabolism of statin medications. The biochemical bases of adverse reactions to statin drugs and their correlation with polymorphisms in metabolic enzymes and transporters are summarized. Next, we mainly focus on the regulatory roles of transcription factors and epigenetic modifications in regulating the gene expression of statin biochemical machinery. The recommendations for future therapies are finally proposed by targeting the central regulatory factors of statin metabolism.

With the vigorous development of football, research on youth football has garnered significant attention from scholars, leading to an increase in published findings. However, there is currently no comprehensive retrospective study that examines the status, hotspots, and trends of research in this field. This study employed Cite Space, a visual bibliometric software, to systematically review and analyze 1637 articles from the Web of Science (WOS) and China Knowledge Infrastructure Project (CNKI) databases up to January 2024. The primary objective was to examine the sources, authors, institutions, regions, citations, as well as keywords, and clustering of these articles to identify the global research hotspots and trends in youth football. The study concluded that the number of research articles in this field has been decreasing annually, and the research hotspots are exhibiting a gradual downward trend. The primary research institutions are comprehensive universities, supplemented by research centers and hospitals. The United States, the United Kingdom, Spain, and China have produced substantial research results in this area, and collaboration among researchers is relatively strong, indicating a positive development trajectory. Current research hotspots include sports monitoring and evaluation, sports injury and risk, talent identification and development, sports performance, the integration of sports and education, school football, and youth training systems. This finding provides a comprehensive overview of the research landscape in this field and presents opportunities for researchers to pursue further in-depth investigations.

Background: The distribution of adverse events (AEs) triggered by immune checkpoint inhibitors (ICIs) across different cancer types has never been demonstrated.

Methods: Randomised controlled trials exclusively assessing ICI monotherapy in cohorts of over 100 patients were considered. Our primary outcome was a comprehensive summary of the distribution of all-grade treatment-related adverse events (TRAEs) as well as serious TRAEs (CTCAE grade 3 or higher) across different malignancies. The study is registered with PROSPERO CRD42023387934.

Findings: 75 trials that enrolled over 100 patients were included. While investigating the incidence of each TRAE across various cancers, we found special linkages existed between certain TRAEs and particular cancer types. In anti-PD-1 monotherapy group, melanoma patients experienced the most frequent fatigue (31.1 %, 95 % CI 29.7%-32.5 %); the incidences of severe pneumonitis and other respiratory disorders were highest in Hodgkin lymphoma (4.1 %, 95 % CI 1.5%-8.6 %; 4.1 %, 95 % CI 1.5%-8.6 %, respectively). Among individuals undergoing single-agent anti-PD-L1, higher frequency of all-grade pruritus occurred in 19.0 % of renal cell carcinoma (RCC) patients (95 % CI 15.2%-23.2 %), and the highest probability of developing other severe musculoskeletal disorders was observed in patients with RCC (6.2 %, 95 % CI 4.0%-9.0 %). In anti-CTLA-4 monotherapy, the incidences of both all-grade and severe diarrhea occurred most frequently in prostate cancer patients (41.9 %, 95 % CI 37.9%-47.9; 14.8 %, 95 % CI 11.5%-18.7 %, respectively).

Interpretation: This is the first comprehensive study addressing the distribution of various TRAEs across cancer types. Our research emphasizes the significance of considering cancer-specific TRAEs when using ICIs for treatment.

Many approaches have been implemented in order to reduce the emissions of particular pollutants without compromising engine performance. Cotton and castor mixed seed oil was chosen for the current study due to their distinct fatty acid composition and potential as a feedstock for bio-additives. Three fuel samples-99 % diesel and 1 % blended fuel (cottonseed oil + castor seed oil), 99.50 % diesel and 0.50 % (cottonseed oil + castor seed oil) blended fuel, and 100 % diesel fuel-are examined. Gas chromatography was used to assess the fatty acid makeup of the substances under investigation. A TBMC8 test bench was used to measure the performance and exhaust emissions characteristics of the diesel fuel containing additives of cotton and castor seed oil. Brake-specific fuel consumption (BSFC), brake thermal efficiency (BTE), engine torque, and emission characteristics of the diesel with additives are measured by adjusting an engine load at 0 %, 20 %, 40 %, 60 %, and 80 %. For D99 (cottonseed oil + castor seed oil) 1, BSFC, BTE, and engine torque at 20 % engine load are 0.757 kg/kWh, 32.98 %, and increased by 1.1 %, respectively. When engine load increased, BSFC slightly increased by 1.1 %. Unlikely, as an engine load increases, there is a modest drop in both BTE and engine torque. Due to the increased oxygen content of bio-additives, which aids in CO oxidization during combustion, carbon monoxide (CO) emissions have dropped by 1.5 % for engine loads ranging from 0 % to 80 %. The higher oxygen content of biodiesel significantly reduced CO emissions, however higher oxygen percentages in blends of biodiesel led to a rise in CO2 emissions. Because cotton and castor blended additives ignited more quickly, NOx increased. Nevertheless, all fall within the allowed range of the ASTM standard.

Aim: Transgender people face many unique challenges. Thus, some of them report excessive use of social media. Our aim was to identify the frequency of social media addiction and to investigate the factors associated with problematic social networking sites use exclusively amongst transgender adults in times of the Covid-19 pandemic.

Subjects: We used data from the "Transgender Survey" HH-TPCHIVG (n = 104 in the analytical sample). Transgender people from self-help groups were involved in gathering information about gender-affirming surgery at a German hospital were included. Specific exclusion criteria did not exist. The validated Bergen Social Media Addiction Scale served as a tool to quantify probable social media addiction.

Results: In sum, 20.5 % of the transgender people are probably addicted to social media. Regressions showed that problematic social networking sites use was significantly positively associated with the presence of a migration background (β = 2.41, p < 0.05), and a higher frequency of sports activities.

Conclusion: In conclusion, our study stressed the challenge of probable social media addiction among transgender people. Knowledge about the correlates of problematic social networking sites use may assist in addressing individuals at risk. The associations identified in this study could be explained, by, among other things, body dissatisfaction (especially with regard to sporting activities) or increased internet contacts (for people with a migration background). Efforts to reduce social media addiction (e.g., awareness-raising, promotion of offline activities, using role models) could prove effective in this group, pending longitudinal research.

Background: Growing evidence indicates that disruptions in mitochondrial quality management contribute to the development of acute kidney injury (AKI), incomplete or maladaptive kidney repair, and chronic kidney disease. However, the temporal dynamics of mitochondrial quality control alterations in relation to renal injury and its recovery remain poorly understood and are addressed in this manuscript.

Method: ology: Male Wistar rats (n = 60) were subjected to varying durations of ischemia and reperfusion. Ischemia was instigated by clamping both renal arteries and for reperfusion, the clamps were removed to restore the blood flow. Renal injury, physiological function, mitochondrial assessment, and cellular mediators were analyzed.

Results: Prolonging ischemia duration reduces bioenergetic function while disrupting the balance of mitochondrial fusion, fission, and mitophagy at the gene expression level while maintaining intact mitochondrial copy number. However, reperfusing a kidney after 45 min of ischemia with varying reperfusion times exacerbates mitochondrial dysfunction and significantly decreases mitochondrial copy number. These declines are particularly evident at 24 h of reperfusion, with some parameters improving by 7 days of reperfusion. Despite these improvements, 7 days of reperfusion did not correlate with renal injury indicators (CrCl- 0.46 ± 0.01, BUN-86.29 ± 4.9, Cr-1.75 ± 0.16) following 45 min of ischemia. Conversely, 15 min of ischemia followed by 7 days of reperfusion restored mitochondrial quality and renal function (CrCl- 7.33 ± 0.59, BUN-43.6 ± 3.16, Cr-0.93 ± 0.14).

Conclusion: The above findings emphasize that mitochondrial quality control alters with the extent of ischemia and subsequent reperfusion time, impacting not only mitochondrial copy number but also the resilience of mitochondria during tissue repair.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. It is characterized by inflammation and fibrosis in the lung parenchyma and interstitium. Given its poor prognosis and limited treatment options, understanding the underlying molecular mechanisms is crucial. Recent evidence suggests that lipid metabolism plays a pivotal role in IPF pathogenesis, however, the precise mechanisms remain poorly understood. To address this, we analyzed 12 bulk RNA-seq and 2 single-cell RNA-seq datasets from the GEO database using machine learning approaches. As a result, we identified four key lipid-related genes-PPARG, SPP1, CASP3, and PECAM1-that are expressed across various cell types. Specifically, in alveolar macrophages (AMs), we observed that PPARG was significantly downregulated, while SPP1 was highly expressed. Importantly, PPARG serves as a transcriptional regulator of SPP1, which in turn mediates intercellular signaling via CD44. Based on these findings, we propose a novel PPARG/SPP1/CD44 signaling pathway in AMs, which modulates lipid metabolism and likely contributes to the progression of fibrosis in IPF. Moreover, network pharmacology analysis identified several herbal compounds that target PPARG, offering potential therapeutic opportunities. In conclusion, these findings highlight the critical role of lipid metabolism in IPF and present novel molecular targets for the development of future therapeutic strategies.

The applicability of cellulose and its derivatives is greatly depends on their attributes such as aspect ratio, morphology, surface chemistry, crystallinity, as well as their thermal and mechanical properties. However, these attributes can alter according to the utilized raw material, size classifications, extraction techniques, or fibrillation methods. Among these, the effect of raw material particle size on cellulose properties has received limited attention in scientific studies. Therefore, this study aimed to investigate the effect of different particle sizes of spent coffee grounds (SCG) (A: 850-1400 μm, B: 500-850 μm, C: 355-500 μm) on the physicochemical properties of TEMPO-oxidized cellulose (TOC). The freez-dried TOC was characterized in terms of functional groups, morphology, width diameter, crystallinity, carboxyl content, charge density, thermal properties, and re-dispersibility in water. Successful oxidation in all samples was confirmed by the presence of a sodium carboxylate peak in the FTIR spectrum. Higher thermal resistance, carboxyl content, as well as improved physical stability of the re-dispersed suspension were observed in A-TOC sample. Unlike B and C-TOC, A-TOC was favored sample for obtaining fibrillated cellulose with crystallinity of 49.92 %. In contrast, production process significantly damaged the crystalline regions in finer particles and reduced the crystallinity of B and C-TOC to values ranging from 35 to 37 %. In conclusion, finer SCG particles were highly sensitive to reaction conditions and showed high tendency toward dissolution, which make them unsuitable candidates for fiber fabrication. In terms of SCG, only coarse particles (A: 850-1400 μm) were found to be ideal for producing oxidized cellulose fibers.