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Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of pigmentation. Among various hypotheses proposed for the pathogenesis of vitiligo, oxidative stress-induced immune response that ultimately leads to melanocyte death remains most widely accepted. Oxidative stress which causes elevated levels of reactive oxygen species (ROS) can lead to dysfunction of molecules and organelles, triggering further immune response, and ultimately melanocyte death. In recent years, a variety of cell death modes have been studied, including apoptosis, autophagy and autophagic cell death, ferroptosis, and other novel modes of death, which will be discussed in this review in detail. Oxidative stress is also strongly linked to these modes of death. Under oxidative stress, ROS could induce autophagy by activating the Nrf2 antioxidant pathway of melanocytes. However, persistent stimulation of ROS might eventually lead to excessive activation of Nrf2 antioxidant pathway, which in turn will inactivate autophagy. Moreover, ferroptosis may be triggered by oxidative-related transcriptional production, including ARE, the positive feedback loop related to p62, and the reduced activity and expression of GPX4. Therefore, it is reasonable to infer that these modes of death are involved in the oxidative stress response, and that oxidative stress also acts as an initiator for various modes of death through some complex mechanisms. In this study, we aim to summarize the role of oxidative stress in vitiligo and discuss the corresponding mechanisms of interaction between various modes of cell death and oxidative stress. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of vitiligo.

The HIV-1 capsid has emerged as a highly attractive drug target due to its highly conserved sequence and critical role in the viral life cycle. By disrupting interactions between capsid proteins and impairing the proper assembly or disassembly of the capsid, the inhibitors can effectively suppress HIV-1 replication and infection. Based on this mechanism, numerous small-molecule agents targeting the HIV-1 capsid protein have been developed to date. In this review, we report the latest advances in such inhibitors and delve into their molecular mechanisms of action. We find a focus on small molecules modulating capsid stability and their assembly/disassembly. Hopefully this study will further enhance the understanding of HIV-1 inhibition mechanisms, facilitating the future exploration of novel capsid inhibitors.

Background/Objective: The prevention and treatment of alcoholic liver disease (ALD) urgently require safe and effective nutritional intervention strategies. Polyphenol extracts from sugarcane molasses (SP) show antioxidant and anti-inflammatory potential, yet their protective effects against ALD have not been elucidated. This study explored the therapeutic potential of SP in alcohol-induced chronic liver damage. Methods: A graded alcohol concentration-induced liver damage model was established in C57BL/6J mice to systematically evaluate SP’s regulatory effects on liver function markers, lipid metabolism, oxidative stress indicators, inflammatory factors, and related molecular mechanisms through a 10-week nutritional intervention. Results: The results demonstrated that SP intervention significantly inhibited the liver index, alanine aminotransferase and aspartate aminotransferase activities, and triglyceride and total cholesterol accumulation in mice. SP enhanced antioxidant enzyme activities in a dose-dependent manner, with the high-dose group increasing catalase activity by 161.19% and superoxide dismutase activity by 22.97%. Furthermore, SP significantly reduced the levels of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, thereby alleviating hepatic inflammatory infiltration. Mechanistic studies revealed that SP effectively mitigated alcohol-induced oxidative stress and inflammatory injury by inhibiting cytochrome P450 2E1 overexpression, regulating the Kelch-like ECH-associated protein 1 signaling pathway, and suppressing nuclear factor-kappa B pathway activation. Conclusions: The findings reveal that SP mitigates ALD via synergistic antioxidant and anti-inflammatory mechanisms, providing a novel strategy for high-value utilization of sugarcane molasses byproducts in agricultural industries. Future studies should focus on the contribution of the different phenolics in SP and validate their specific hepatoprotective mechanisms.

Background Restricted mean survival time (RMST) quantifies survival benefits in single-endpoint analysis, while restricted mean time lost (RMTL) measures event-related time loss in competing risks settings. Both provide clinically intuitive interpretations of treatment effects without relying on proportional hazards assumptions or parametric distributions. While existing RMST/RMTL methods focus primarily on two-group comparisons, multi-arm trials are common in practice. However, asymptotic approaches for these metrics suffer from inflated type I error in small samples, limiting their reliability. Methods We propose a global test framework using variable transformation methods (e.g., log, clog-log, arcsine square root, logit), which is applicable to multi-group comparisons of RMST and extends to RMTL in the presence of competing risks. Monte-Carlo simulations were conducted to evaluate type I error and power under various scenarios, and two illustrative examples were provided. Results Simulations demonstrated that transformed RMST and RMTL global tests effectively controlled type I error across small samples and high censoring rates, while improving power compared to untransformed methods. For single-endpoint analysis, the RMST arcsine square root transformation is recommended. In competing risks settings, RMTL logit transformation is preferred when the event of interest occurs more frequently than competing events, whereas clog-log transformation performs better when competing events dominate. Conclusions The proposed transformation-based global tests offer researchers a flexible, assumption-free tool to compare treatment effects across multiple groups with enhanced reliability and interpretability. Additionally, an R package \"compRM\" was developed to implement the proposed methods.

Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.

Autophagy is a process involving the self-digestion of components that participates in anti-oxidative stress responses and protects cells against oxidative damage. However, the role of autophagy in the anti-oxidative stress responses of melanocytes remains unclear. To investigate the role of autophagy in human epidermal melanocytes, we knocked down and overexpressed ATG7, the critical gene of autophagy, in normal human epidermal melanocytes. We demonstrated that ATG7-dependent autophagy could affect melanin content of melanocytes by regulating melanogenesis. Moreover, suppression of ATG7-dependent autophagy inhibits proliferation and promotes oxidative stress-induced apoptosis of melanocytes, whereas enhancement of ATG7-dependent autophagy protects melanocytes from oxidative stress-induced apoptosis. Meanwhile, deficiency of ATG7-dependent autophagy results in premature senescence of melanocytes under oxidative stress. Notably, we verified that ATG7-dependent autophagy could alter oxidative stress homeostasis by regulating reactive oxygen species (ROS) production, nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, and the activity of several antioxidant enzymes in melanocytes. In conclusion, our study suggested that ATG7-dependent autophagy is indispensable for redox homeostasis and the biological functions of melanocytes, such as melanogenesis, proliferation, apoptosis, and senescence, especially under oxidative stress.

The behavior of calcareous sand under repeated impact considerably differs from that of silica sand. Notably, calcareous sand is important in engineering projects in the South China Sea, such as pile driving. To understand the behavior of calcareous sand under multiple impacts, the improved split Hopkinson pressure bar (SHPB) system was selected for one-dimensional impact tests of silica and calcareous sand with particle sizes of 0.25–0.50 mm. The sand specimens were impacted 1, 3, 7 and 10 times. The test results reveal that the dynamic apparent stiffness of silica sand is approximately 6–8 times that of calcareous sand. The dynamic apparent modulus values of the two sands increase with an increase in the number of impacts, N. For calcareous sand, the compression index Cc decreases with an increase in N, and silica sand shows the opposite trend. The yield pressure pc of calcareous sand under impact loading is approximately 40% of that of silica sand. With an increase in N, the energy absorption capacity, energy dissipation rate and damage variables of the two sands exhibit a downward trend. In addition, the energy absorption efficiency of calcareous sand is better than that of silica sand. During the process of impact, a large number of sand particles will break, and particle breakage will change the particle size distribution (PSD), thereby significantly affecting the physical and mechanical properties of the corresponding soil. Based on the test results and fractal theory, an evolution model is established to characterize the PSD evolution in the breakage state for uniformly graded calcareous sand. Moreover, a Markov chain model is proposed to describe the PSD evolution of nonuniformly graded specimens. The predicted results of both models show agreement with the experimental values.

Background According to long-term follow-up data of malignant tumor patients, assessing treatment effects requires careful consideration of competing risks. The commonly used cause-specific hazard ratio (CHR) and sub-distribution hazard ratio (SHR) are relative indicators and may present challenges in terms of proportional hazards assumption and clinical interpretation. Recently, the restricted mean time lost (RMTL) has been recommended as a supplementary measure for better clinical interpretation. Moreover, for observational study data in epidemiological and clinical settings, due to the influence of confounding factors, covariate adjustment is crucial for determining the causal effect of treatment. Methods We construct an RMTL estimator after adjusting for covariates based on the inverse probability weighting method, and derive the variance to construct interval estimates based on the large sample properties. We use simulation studies to study the statistical performance of this estimator in various scenarios. In addition, we further consider the changes in treatment effects over time, constructing a dynamic RMTL difference curve and corresponding confidence bands for the curve. Results The simulation results demonstrate that the adjusted RMTL estimator exhibits smaller biases compared with unadjusted RMTL and provides robust interval estimates in all scenarios. This method was applied to a real-world cervical cancer patient data, revealing improvements in the prognosis of patients with small cell carcinoma of the cervix. The results showed that the protective effect of surgery was significant only in the first 20 months, but the long-term effect was not obvious. Radiotherapy significantly improved patient outcomes during the follow-up period from 17 to 57 months, while radiotherapy combined with chemotherapy significantly improved patient outcomes throughout the entire period. Conclusions We propose the approach that is easy to interpret and implement for assessing treatment effects in observational competing risk data.

Dietary selenium (Se) is an essential component that supports fish growth and the immune system. This review attempts to provide insight into the biological impacts of dietary Se, including immunological responses, infection defense, and fish species growth, and it also identifies the routes via which it enters the aquatic environment. Dietary Se is important in fish feed due to its additive, antioxidant, and enzyme properties, which aid in various biological processes. However, excessive intake of it may harm aquatic ecosystems and potentially disrupt the food chain. This review explores the diverse natures of dietary Se, their impact on fish species, and the biological methods for eliminating excesses in aquatic environments. Soil has a potential role in the distribution of Se through erosion from agricultural, industrial, and mine sites. The research on dietary Se’s effects on fish immune system and growth can provide knowledge regarding fish health, fish farming strategies, and the health of aquatic ecosystems, promoting the feed industry and sustainable aquaculture. This review provides data and references from various research studies on managing Se levels in aquatic ecosystems, promoting fish conservation, and utilizing Se in farmed fish diets.

Betaine is a kind of zwitterionic surfactant with both positive and negative charge groups on the polar head, showing good surface activity and aggregation behaviors. The interfacial adsorption, structures and properties of n-dodecyl betaine (NDB) at different surface coverages at the air–water interface are studied through molecular dynamics (MD) simulations. Interactions between the polar heads and water molecules, the distribution of water molecules around polar heads, the tilt angle of the NDB molecule, polar head and tail chain with respect to the surface normal, the conformations and lengths of the tail chain, and the interfacial thickness of the NDB monolayer are analyzed. The change of surface coverage hardly affects the locations and spatial distributions of the water molecules around the polar heads. As more NDB molecules are adsorbed at the air–water interface, the number of hydrogen bonds between polar heads and water molecules slightly decreases, while the lifetimes of hydrogen bonds become larger. With the increase in surface coverage, less gauche defects along the alkyl chain and longer NDB chain are obtained. The thickness of the NDB monolayer also increases. At large surface coverages, tilted angles of the polar head, tail chain and whole NDB molecule show little change with the increase in surface area. Surface coverages can change the tendency of polar heads and the tail chain for the surface normal.