Explore the vast range of titles available.

After the introduction of anticholinergic drugs for the treatment of overactive bladder (OAB), the discovery of β-adrenergic agonists has helped reduce the side effects associated with the former. Currently, the two available medications, mirabegron and vibegron, are β-adrenergic agonists. However, clinical practitioners are still faced with the dilemma of which drug to choose. To analyze and compare the efficacy and adverse effects of the two medications. A literature search was conducted to identify randomized controlled trials using mirabegron and vibegron for the treatment of OAB. Databases such as PubMed, Web of Science, Cochrane Library, and Embase were searched. The search cutoff date was July 25 2024. Data extraction and quality assessment were performed using standardized methods. A meta-analysis was then conducted using RevMan software and a random-effects model, with studies weighted according to sample size and variance. Heterogeneity was assessed using the I² statistic. All statistical analyses were performed using RevMan, and results were presented as effect sizes (e.g., mean difference or risk ratio). Three randomized controlled trials compared the safety and efficacy of mirabegron and vibegron head-to-head, involving 368 patients. The trials, each lasting 8 or 12 weeks. The trials compared the changes in various indices of the OABSS (Overactive Bladder Symptom Score) between the two drugs. The statistical methods used in the analysis included Mean Difference (MD), 95% Confidence Interval (CI), p-value, and I² statistic. For OABSS: MD =  0.38, 95% CI =  - 0.19 to 0.95, p =  0.28, I² =  21%; for Q1: MD =  0.08, 95% CI =  - 0.01 to 0.26, p =  0.31, I² =  4%; for Q2: MD =  0.08, 95% CI =  - 0.21 to 0.37, p =  0.67, I² =  0%; for Q3: MD =  0.05, 95% CI =  - 0.45 to 0.56, p =  0.90, I² =  0%; for Q4: MD =  - 0.21, 95% CI =  - 0.68 to 0.27, p =  0.35, I² =  0%. The relative risk (RR) of adverse effects between the two drugs was: RR =  0.87, 95% CI =  0.57 to 1.34, p =  0.27, I² =  25%; for constipation: RR =  0.73, 95% CI =  0.37 to 1.43, p =  0.27, I² =  25%; and for dry mouth: RR =  0.98, 95% CI =  0.42 to 2.30, p =  0.78, I² =  0%. There appears to be no statistically significant difference in efficacy and safety between mirabegron and vibegron for OAB patients. Further high-quality prospective studies are needed to confirm these results.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis, and its clinical management remains a significant challenge due to the high recurrence rates and limited treatment options. Despite advances in understanding the molecular mechanisms underlying ACC, no reliable biomarkers have been validated for routine clinical use. We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) database (n=79) and Genotype Tissue Expression (GTEx) database (n=128) to investigate the expression of VGF in ACC and normal adrenal tissues. Gene expression levels of VGF were quantified and correlated with clinicopathological features and survival outcomes. Statistical methods included Cox proportional hazards models and Kaplan-Meier analysis, while Gene Set Enrichment Analysis (GSEA) was utilized to identify relevant biological pathways associated with VGF expression. Clinical data from 7 ACC patients from YANTAI YUHUANGDING Hospital were also analyzed. The expression of VGF in ACC and normal adrenal gland tissue was further validated through IHC experiments. Our results demonstrate that VGF expression is elevated in ACC tissues compared to normal adrenal tissues and is significantly associated with advanced disease stages, lymph node involvement, metastasis and poor overall survival. VGF levels also correlate with immune cell infiltration, including Th2 cells, T helper cells, and Neutrophils. Importantly, our study establishes VGF as a potential prognostic biomarker for ACC and highlights its role in tumor progression and immune modulation. Additionally, GSEA analysis suggests that VGF is involved in cytokine receptor interaction and the P13K-Akt signaling pathway, possibly relating to tumor immunity. VGF could serve as a valuable marker for patient stratification, monitoring disease progression, and predicting responses to immunotherapies. Future studies should focus on investigating circulating VGF levels as a non-invasive biomarker for ACC to improve clinical management and treatment outcomes.

Biochar prepared by thermal decomposition of sewage sludge is a new adsorbent for sludge resource utilization and aquatic environmental treatment. In this study, sewage sludge was used as raw material for the preparation of pyrolysis sludge-based biochar. In addition, montmorillonite (Mt) and nano zero-valent iron (nZVI) were used to modify sludge-based biochar in different combinations to improve its adsorption capacity of nitrogen and phosphorus in water, and the best modification scheme was selected. The physicochemical properties of the biochar were analyzed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The results showed that Mt and nZVI could improve the specific surface area and enrich the surface functional groups. The results on kinetics and equilibrium isotherms showed that sludge-based biochar modified by Mt coupled with nZVI (nZVI@MBC) had the best adsorption effect on NH4+ and PO43−. And its theoretical maximum saturation adsorption capacity for NH4+ and PO43− was 34.84 mg·g−1 and 294.12 mg·g−1, respectively. Our results were in the forefront of existing literature on modified sludge-based biochar. The adsorption mechanisms of nZVI@MBC for NH4+ and PO43− mainly include ligand exchange, electrostatic attraction and ionic bond. In addition, nZVI@MBC can also remove PO43− by chemical precipitation and coprecipitation of iron corrosion products.

P-nitrophenol (PNP), a highly toxic carcinogen, is very stable due to its benzene structure. Advanced oxidation technology is becoming the main means for degrading it. A nano iron-cobalt (Co-nZVI) catalyst, supported by granular activated carbon (GAC), was prepared using liquid-phase reduction, and sodium persulfate’s (PS’s) potential to degrade PNP was studied. The Co-nZVI/GAC nanocomposites were classified, and effects of PS dosage, Co-nZVI/GAC dosage, material system type, PNP concentration, initial pH, and material reuse rate on the reaction were investigated. Activated carbon successfully supported iron and cobalt. At 1 mmol/L of PS, the maximum PNP degradation rate was 99.19%, which was unachievable at other dosages. With only Co-nZVI/GAC present, the rate was 69.8%; with activated persulfate present, it increased to 99.19%. The activated PS system was relatively stable under acidic conditions. Catalysis was induced by adding Co-nZVI/GAC (1.5 g/L). When added four times, the catalytic rate was 57%. Liquid chromatography–mass spectrometry (LC-MS) showed that PNP degradation involves the transfer of PNP to p-benzoquinone (PBQ), the main activators being iron(II) and iron(III) and the key active substances being sulfate (SO42−) and hydroxide (·OH). In conclusion, Co-nZVI/GAC-activated PS effectively removes PNP.

The crosstalk between cancers and the immune microenvironment plays a critical role in malignant progression. FMS-like tyrosine kinase 3 (FLT3) is a frequently mutated gene in acute myeloid leukemia (AML). However, its role in solid cancers remains poorly understood. We analyzed the frequency of FLT3 alterations, its mRNA expression levels, and its prognostic implications across multiple cancer types. Additionally, we explored genes co-expressed with FLT3 and performed gene ontology analysis to identify associated biological processes. We also examined the relationship between FLT3 expression and markers of various immune cells, tertiary lymphoid structures (TLSs), and epithelial-mesenchymal transition. Furthermore, we validated these findings in our own cohort of hepatocellular carcinoma (HCC) patients. We found that FLT3 alteration and expression were both significantly upregulated in AML and were associated with poor prognosis, which is opposite to its role in solid cancers. The genes co-expressed with FLT3 in solid cancers were correlated with the regulation of the immune microenvironment. FLT3 was positively correlated with the formation of TLSs in only solid cancers, which was especially relevant to central memory T cells. We also found that FLT3 was positively correlated with the infiltration of NK cells, B cells, and DCs. It also positively correlated with the occurrence of apoptosis in solid cancers, but exhibited opposite roles in AML. The structural factors of the TLSs were positively correlated with FLT3 in solid cancers, but exhibited a negative correlation in AML. Meanwhile, we further validated the above conclusions in our own HCC cohort and demonstrated that FLT3 could serve as a predictive indicator of PD-1 treatment efficacy in HCC. In summary, the role of FLT3 is different in AML and solid cancers. FLT3 is associated with dendritic cell infiltration, tertiary lymphoid structure construction, and predict response to checkpoint inhibitors immunotherapy in HCC.

Cancer stem cells (CSCs) are a key subpopulation within tumors, characterized by their self-renewal and differentiation potential, and they drive tumor initiation, progression, metastasis, and recurrence. Recent epitranscriptomic studies have revealed that RNA modifications, including m 6 A, m 5 C, ac 4 C, m 7 G, and m 1 A, play critical roles in maintaining CSC stemness, determining cell fate, reprogramming metabolism, and promoting therapy resistance. This review systematically summarizes the functions of different RNA modifications and their associated enzymes in CSCs. We also discuss how RNA modifications regulate core CSC signaling pathways, such as Wnt/β-catenin, Notch, Hedgehog, PI3K–AKT–mTOR, JAK/STAT, Hippo/YAP, and TGF-β/SMAD, and we highlight strategies targeting RNA modifications for CSC intervention along with their potential challenges. These findings suggest that RNA modifications and their regulators represent promising therapeutic targets in CSCs, providing a rationale for developing highly selective or combination treatment strategies.

The main objective of this experiment was to study the metabolism of arginine in juvenile largemouth bass ( Micropterus salmoides ). A total of 300 healthy fish (average weight of 25 ± 0.5 g) were randomly assigned to ten groups. Experimental fish were orally administered or intraperitoneally injected with 0.9% sodium chloride, arginine, arginine-aspartate, citrulline, and glutamate solutions, respectively. They were euthanized at 10, 30, 60, 120, and 240 min after oral administration or intraperitoneal injection, and various tissue samples were subsequently collected for analysis. The results revealed that serum ornithine and citrulline concentrations of largemouth bass were significantly increased by oral administration of arginine or arginine-aspartate ( P  < 0.05). Intraperitoneal injection of arginine or arginine-aspartate solution significantly elevated the concentrations of ornithine and citrulline in the serum, liver, kidney, and muscles ( P  < 0.05). The concentrations of citrulline, ornithine, and arginine in serum and muscle increased significantly at 4 h after intraperitoneal injection of glutamate ( P  < 0.05). Intraperitoneal injection of citrulline significantly increased the concentrations of ornithine and arginine in the serum and muscles ( P  < 0.05). The research findings demonstrate that both free and small peptide forms of arginine were rapidly degraded to ornithine due to the high arginase activity in various tissues of largemouth bass. Additionally, the pathway of synthesizing citrulline from glutamate and then arginine from citrulline may exist in largemouth bass, but the exact location of this synthesis process may differ from that found in mammals.

The purpose of this meta-analysis was to evaluate the efficacy and safety of the once-daily use of 5 mg tadalafil in the treatment of patients with premature ejaculation. The databases MEDLINE/PubMed, EMBASE, and Cochrane Library from January 1980 until December 2024 were searched to identify randomized controlled trials (RCTs) that referred to the use of tadalafil for the treatment of premature ejaculation. A systematic review and meta-analysis was conducted. Five publications involving 397 patients were included in the meta-analysis. No statistically significant difference was identified between tadalafil and placebo for intravaginal ejaculatory latency time (IELT; mean difference [MD] = 68.43; 95% confidence interval [CI] = [−12.59 to 149.45]; p = .10) and Arabic index of premature ejaculation (AIPE; MD = 11.44; 95% CI = [−11.79, 34.66]; p = .33). Tadalafil appeared to improve the score of the premature ejaculation diagnostic tool (PEDT; MD = −0.30; 95% CI = [−0.57, −0.03]; p = .03). In terms of adverse events, the tadalafil group was significantly higher than the placebo group for headache (odds ratio [OR] = 16.06, 95% CI = [3.80, 67.94], p = .0002), back pain and myalgia (OR = 21.76, 95% CI = [4.17, 113.53], p = .0003), flushing (OR = 6.05, 95% CI = [1.05, 34.92], p = .04), and dyspepsia (OR = 10.27, 95% CI = [1.90, 55.96], p < .007). Our meta-analysis indicates that the once-daily use of 5 mg tadalafil had no statistically significant effect in the treatment of premature ejaculation. Meanwhile, the tadalafil therapy showed a higher risk of complications.

Continuing global warming intensifies the thermal stress suffered by fish, urgently necessitating effective mitigating techniques. This study aims to investigate the mechanisms by which astaxanthin alleviates oxidative stress and inflammatory damage induced by thermal stress. Under thermal stress, an increase in oxidative stress was observed in the myocytes of Micropterus salmoides , however, intervention of astaxanthin exerted a notable alleviating effect on oxidative stress. Evidence of thermal stress experiment on primary myocytes indicates that astaxanthin resists thermal stress by enhancing the activity of antioxidant enzymes, heat shock proteins and activating the antioxidant gene Nrf2 . Further integrated multi-omics analysis revealed a significant upregulation of several antioxidant biomarkers, such as Glutathione (GSH), glutathione peroxidase (GPX) and glutathione S-transferase (GST). This study proposes the hypothesis that astaxanthin may enhance the GSH-dependent endogenous antioxidant enzyme system by activating the Keap1-Nrf2 signaling pathway. Notably, the supplementation of astaxanthin, compared to thermal stress alone, inhibited the expression of inflammatory factors and apoptosis-related genes, including TLR2 , IL8 , EIF4E , IL2RB , CASP3 , and CASP9 . These results, combined with the observed inhibition of the Toll-like receptor signaling pathway and the NF-κB signaling pathway, indicate that the TLR2/4-NF-κB signaling pathway plays a crucial role in mediating the alleviation of oxidative stress-induced inflammatory damage by astaxanthin. Furthermore, astaxanthin remodels amino acid and lipid metabolism under thermal stress, establishing an adaptive anti-thermal stress metabolic mechanism that encompasses both phase I and phase II metabolism. These findings offer novel insights into the mechanisms underlying astaxanthin-induced protection against oxidative stress and inflammatory damage.

This study examined the effects of feeding largemouth bass ( Micropterus salmoides ) with diets containing different doses of astaxanthin (0, 50, 100, 150, and 200 mg/kg) for 8 weeks. The results showed that the values of weight gain significantly increased from 620.32 ± 50.38% to 826.14 ± 33.49% as dietary astaxanthin levels increased from 0 mg/kg to 100 mg/kg. When the astaxanthin level exceeded 150mg/kg, the weight gain rate showed a downward trend, but there was no significant difference among of the 100, 150 and 200 mg/kg groups. The feed conversion ratio (FCR) and protein efficiency ratio (PER) were also improved by adding astaxanthin to diets ( P < 0.05). Meanwhile, adding astaxanthin to the feed increased the length and thickness of intestinal villus and muscle layer thickness ( P < 0.05). The astaxanthin supplementation increased the expression of the NF-E2-related factor ( Nrf2 ) gene and reduced malondialdehyde (MDA) content and the expression of apoptosis genes Caspase-9 and Caspase-3 ( P < 0.05), indicating that it has a good antioxidant ability. Furthermore, adding astaxanthin increased the content of non-specific immune markers and decreased the expression levels of the inflammatory factors interleukin-15 ( IL-15 ) and tumor necrosis factor-α ( TNF-α ). Moreover, fish fed diets with astaxanthin exhibited lower blood cortisol levels ( P < 0.05). The proportions of C20:4n6 (ARA) and C20:5n3 (EPA) in the liver decreased with increasing dietary astaxanthin levels. Based on WGR and SGR values, the optimal addition level of astaxanthin in largemouth bass feed is 134.8 mg/kg ~ 135.75 mg/kg. In summary, the appropriate dietary astaxanthin enhanced the antioxidant capacity and immune response of largemouth bass and had a positive effect on its intestinal health.