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Cisplatin is widely employed in clinical oncology as an anticancer chemotherapy drug in clinical practice and is known for its severe ototoxic side effects. Prior research indicates that the accumulation of reactive oxygen species (ROS) plays a pivotal role in cisplatin's inner ear toxicity. Hesperidin is a flavanone glycoside extracted from citrus fruits that has anti-inflammatory and antioxidant effects. Nonetheless, the specific pharmacological actions of hesperidin in alleviating cisplatin-induced ototoxicity remain elusive. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical mediator of the cellular oxidative stress response, is influenced by hesperidin. Activation of Nrf2 was shown to have a protective effect against cisplatin-induced ototoxicity. The potential of hesperidin to stimulate Nrf2 in attenuating cisplatin's adverse effects on the inner ear warrants further investigation. This study employs both in vivo and in vitro models of cisplatin ototoxicity to explore this possibility. Our results reveal that hesperidin mitigates cisplatin-induced ototoxicity by activating the Nrf2/NQO1 pathway in sensory hair cells, thereby reducing ROS accumulation, preventing hair cell apoptosis, and alleviating hearing loss. [ABSTRACT FROM AUTHOR]

Multivariate regression is a widely used technique for large-scale statistical applications. In this paper, we propose a novel method for the multivariate regression model, called multivariate weighted lasso (MWL). We consider the heteroscedasticity in the noise matrix and introduce an adjustable weight to calibrate the fitting residuals of different responses. The proposed method shows an advantage in complex multivariate regressions with heteroscedasticity. To implement the procedure, an efficient algorithm is provided based on the multivariate coordinate descent. We provide theoretical guarantees for the proposed method. Numerical simulations and financial applications are conducted using the proposed and other existing methods. The results indicate that the proposed method performs well in both variable selection and coefficient estimation. [ABSTRACT FROM AUTHOR]

In the treatment of uveal melanoma (UVM), histone deacetylase inhibitors (HDACi) have emerged as a promising epigenetic therapy. However, their clinical efficacy is hindered by the suboptimal pharmacokinetics and the strong self‐rescue of tumor cells. To overcome these limitations, reactive oxygen species (ROS)‐responsive nanoparticles (NPs) are designed that encapsulate HDACi MS‐275 and the glutamine metabolism inhibitor V‐9302. Upon reaching the tumor microenvironment, these NPs can disintegrate, thereby releasing MS‐275 to increase the level of ROS and V‐9302 to reduce the production of glutathione (GSH) related to self‐rescue. These synergistic effects lead to a lethal ROS storm and induce cell pyroptosis. When combined with programmed cell death protein 1 monoclonal antibodies (α‐PD‐1), these NPs facilitate immune cell infiltration, improving anti‐tumor immunity, converting "immune‐cold" tumors into "immune‐hot" tumors, and enhancing immune memory in mice. The findings present a nano‐delivery strategy for the co‐delivery of epigenetic therapeutics and metabolic inhibitors, which induces pyroptosis in tumors cells and improves the effectiveness of chemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Despite suicide in younger population having become a severe public health issue, information on the prevalence of suicidality among Chinese children and adolescents is still limited. This study aims to estimate the prevalence of suicidal ideation, suicide plans, and suicide attempts in Chinese children and adolescents aged under 18 years. A meta-analysis was conducted based on English and Chinese publications from January 1, 2010 to December 31, 2020 using random-effects models. Based on 132 eligible studies with a combined total of 1,103,309 Chinese children and adolescents below 18 years old, the pooled prevalence of the overall suicidal ideation, suicide plans, and suicide attempts were 15.4% (95% CI [14.3, 16.6]), 6.4% (95% CI [5.5, 7.4]) and 3.5% (95% CI [3.1, 4.1]), respectively. The subgroup analyses showed that there were significant variations of prevalence of suicidal risks across genders, school stages, and geographical areas in mainland China. It was the first systematic review and meta-analysis to show suicidality among younger population aged below 18 years is prevalent in mainland China. This study suggests that gender-age-region-specific prevention and intervention programs should be urgently needed to reduce suicidal risks among Chinese children and adolescents. [ABSTRACT FROM AUTHOR]

A novel and comprehensive resource utilization technology involving the production of biomass fuel rods and the creation of water-retaining and loose media derived from food waste has been developed as a result of the increased focus on the efficient utilization of resources derived from food waste in recent years. This technical procedure produced a novel wastewater stream that was identified as food waste squeezing liquid. The study was primarily concerned with examining the effects of temperature on the anaerobic fermentation method used to produce methane from food waste squeezing liquid and with examining changes in the microbial population during the fermentation process. After 53 days of anaerobic fermentation at the ideal temperature 47 °C, 17 220 mL of gas were produced overall, with peak methane production accounting for 70%~75% of the total gas output. This peak methane production was 2.5 times higher than that observed at 37 °C. It's interesting to note that after the fifth day of fermentation, no methane generation was seen at temperatures of 27 °C, 57 °C, and 67 °C. After performing high-throughput sequencing on the 16S rDNA, the relative abundance of unclassified_d_Bacteria decreased significantly from 83.92% to only 24.16% during fermentation under low oxygen conditions. Under strict anaerobic conditions, the proportion of Clostridium increased dramatically from a mere percentage of just 0.93% to as high as 44.75%, but it eventually dropped down to 5.40% after concluding the fermentation experiment. Subsequently, the relative abundance of unclassified_d_Bacteria rebounded and rose sharply from 24.16% to 68.12%. The findings of this study offer valuable insights into the optimization of anaerobic fermentation temperature selection and the choice of bacterial strains applicable in the practical engineering implementation of food waste squeezing liquid. [ABSTRACT FROM AUTHOR]