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Performance of Five Prognostic Scores in Predicting Short-term Mortality in Patients with Acute-on-chronic Liver Failure
Polymer-free β-cyclodextrins and mefenamic acid inclusion complex nanofibers for enhanced drug solubility and biomedical applications
Curcumin inhibits ferroptosis through dessuccinylation of SIRT5-associated ACSL4 protein, and plays a chondroprotective role in osteoarthritis
Background Ferroptosis of chondrocytes plays a crucial role in the progression of osteoarthritis (OA). This study aimed to explore the role of curcumin (Cur) in interfering with chondrocyte ferroptosis in OA. Methods Rat chondrocytes were treated with 10 ng/mL interleukin-1β (IL-1β) for 48 hours to mimic the OA microenvironment. The protective effects of Cur were evaluated in vitro by assessing cell viability and ferroptosis. Molecular docking was performed to validate the structural interaction between Cur and the SIRT5 protein. Co-immunoprecipitation (CO-IP) confirmed the binding relationship between SIRT5 and ACSL4. Additionally, the efficacy of Cur in alleviating OA progression was assessed in an in vivo OA rat model. Results Cur treatment significantly attenuated IL-1β-induced chondrocyte injury by enhancing cell viability and inhibiting ferroptosis. Cur also markedly reduced global protein lysine succinylation levels. IL-1β suppressed SIRT5 expression, while Cur treatment upregulated SIRT5 expression. The molecular structure of Cur exhibits strong complementarity with the SIRT5 protein, forming a stable complex with high binding affinity. Inhibition of SIRT5 attenuated the protective effects of Cur on chondrocytes and increased ACSL4 succinylation levels. SIRT5 physically interacted with ACSL4, and SIRT5-mediated desuccinylation of ACSL4 repressed its function, thereby mitigating ferroptosis. Cur alleviates OA progression in vivo by inhibiting cartilage destruction, bone erosion, and chondrocyte injury, and by smoothing subchondral bone surfaces. Conclusion Cur protects chondrocytes in vitro by inhibiting ferroptosis and suppresses cartilage degeneration and bone erosion in vivo, demonstrating a chondroprotective role in OA. These effects are mediated through SIRT5-dependent desuccinylation of ACSL4, which regulates ferroptosis pathways.
Clinical Considerations in Validating Global Acute Respiratory Distress Syndrome Definition: Addressing Temporal Dynamics and Confounding Variables
Optimize multi-objective transformation rules of water-sediment regulation for cascade reservoirs in the Lower Yellow River of China
Genome-driven insights into Bacillus safensis strain B7 as a seed coating agent for plant growth promotion and alleviation of biotic and abiotic stresses
Despite the significant increase in the use of plant growth-promoting bacteria (PGPB) in agriculture, there is a dearth of studies addressing the impact of seed coating with PGPB on plant productivity. The main objective of this research is to evaluate the potential of Bacillus safensis strain B7 as a seed coating agent to confer plant growth promotion and tolerance against biotic and abiotic stress. The whole-genome sequencing of strain B7 was also performed to study its genomic features. The effect of seed coating with strain B7 was assessed on seed water uptake, germination and seedling dry weight under controlled conditions. Besides, the direct and indirect effect against biotic stress was evaluated through antifungal activity and potential in stimulating the induced systemic resistance (ISR) under controlled conditions. Afterwards, the effect was evaluated in the field under drought stress conditions, based on the traits of grain yield (GY), straw yield, number of spikes/m2, and thousand kernel weight (TKW). It is noticeable that seed coating with strain B7 resulted in greater and faster water uptake. Germination and plant growth similarly boosted. Strain B7 was able to hamper the mycelial growth of F. culmorum and S. sclerotiorum and to induce ISR, after B. cinerea infection, in melon leaves taken from root-treated plants. In the field, seed coating with strain B7 improved wheat performance under the different environments and mitigated the effect of drought on spikes/m2, GY and TKW. The observed impact on wheat plants is supported by genomic analysis of strain B7 showing the presence of genes related to beneficial plant–bacteria interactions involved in plant colonization, growth promotion and alleviation of stress. Therefore, B. safensis strain B7 has promising applications in the seed treatment industry to increase plant yield and alleviate the impact of stress.
Author Response: Clinical Considerations in Validating Global Acute Respiratory Distress Syndrome Definition – Addressing Temporal Dynamics and Confounding Variables
Low-cost fabrication and comparative evaluation of machine learning algorithms for flexible PDMS-based hexagonal patch antenna
Mapping network structures and dynamics of decentralised cryptocurrencies: The evolution of Bitcoin (2009–2023)
At the beginning of July 2025, the global cryptocurrency market capitalisation reached more than $2.8 trillion, with 1 Bitcoin exchanging for more than $105,000. As cryptocurrencies are becoming part of the global financial infrastructure, monitoring their evolution is crucial for determining whether they can be considered a sustainable long-term financial exchange system. In this paper, we have reconstructed the network structures and dynamics of Bitcoin from its launch in January 2009 to December 2023 and identified its key evolutionary phases. Our results show that network centralisation and wealth concentration increased from the very early years, following a richer-get-richer mechanism. This trend was endogenous to the system, beyond any subsequent institutional or exogenous influence. The evolution of Bitcoin is characterised by three periods, Exploration, Adaptation, and Maturity, with substantial coherent network patterns. Our findings suggest that Bitcoin is a highly centralised structure, with high levels of wealth inequality and internally crystallised power dynamics, which may have negative implications for its long-term sustainability.
Syndromic Testing Using Multiplex Polymerase Chain Reaction vs Conventional Standard of Care Testing: A Prospective Study to Assess the Clinical Response and Cost Effectiveness
Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer
Sex and age differences in the association between routine suicide newspaper reporting and change in admissions of suicidal patients: An investigation at an emergency and critical care center in Tokyo
Background The influence of media reporting on suicide and suicide attempts (SA) has been rigorously studied. Previous studies focused on characteristics like celebrity status, sex and age of suicide decedents, which may facilitate suicide and SA occurrence. These studies have informed guidelines for responsible media reporting. However, the nuanced effects on different sex and age groups of suicidal individuals remain less understood. Methods This study examined the association between the characteristics of initial suicide reports in four major newspapers and the differences in admission numbers (Δs) of SA patients across sex and age groups during pre- and post-article release one-week periods. Data from an Emergency and Critical Care Center from 2012 to 2019 were obtained through a review of medical records. Nonparametric MANOVAs were employed to investigate Δs for sex and age groups of SA patients in relation to sex and age of suicide decedents, incident types, and methods. Significant differences were evaluated using Wilcoxon tests. Results A total of 1,205 articles on 676 suicide incidents and 1,081 SA admissions were analyzed. MANOVAs revealed a significant association between the Δs and the reported suicide methods. Δ for females was positively associated with reports of gas poisoning and other infrequently reported methods, whereas Δ for males was negatively associated with gas poisoning. Δ for younger patients was positively associated with infrequently reported methods and negatively with firearm discharge. No significant associations were found between Δ and sex and age of decedents or incident types. Discussion This study demonstrates a differential impact of suicide news articles reporting gas poisoning, infrequently reported suicide methods, and firearm discharge, on SA patient admissions across sex and age groups. These differences may arise from variations in emotional responses to the suicide methods, which can be understood in both psychological and socio-cultural contexts. Further research is needed to clarify the determinants of differential influences to more effectively address and mitigate the risks of suicide and SAs.
Spectrum of Acute Kidney Injury and its Outcome in Chronic Liver Disease Patients in the Emergency Department
Factors influencing referral among women attending post abortion care at tertiary hospitals in Northern Uganda
How fast-and-frugal trees can inform diagnostic and intervention decisions for enhancing elite athlete performance
The key to fostering the individual potential of an elite athlete lies in deciding what to prioritize in training. Heuristic decision tools such as fast-and-frugal trees (FFTrees) have proven to be effective and suitable for identifying promising determinants in this context. FFTrees are binary decision trees that can make decisions based on only one reason. The objective of this study was to examine the applicability of FFTrees to inform intervention decisions in elite athletes. We aimed to create FFTrees and evaluate their ability to determine individually beneficial interventions. We collected cognitive, psychosocial, and motor-performance diagnostic data from 466 German elite athletes in different sports disciplines. First, we used principal component analysis to identify components representing types of interventions across sports. These served as cues for the FFTrees. As a result, the PCA identified six cues. Two sport-specific FFTrees were created using these six cues. One FFTree was created for trampoline with four cues (relative grip strength, motor cost, motor inhibition, visual selective attention) and 90% correct predictions. The other FFTree was created for volleyball with four cues (motor inhibition, motor cost, countermovement jump, Y-Balance Test) and 75% correct predictions. To conclude, the high accuracy confirms that FFTrees enable data-based decisions for interventions based on sport-specific demands and the preferences of coaches. We argue that FFTrees are beneficial in projects collecting multidisciplinary variables for personalizing interventions in elite athletes. Coaching practice benefits from using FFTrees by providing reference values when an intervention could enhance performance. In the future, we advocate that team sports develop position-specific FFTrees. In conclusion, FFTrees empower decision-makers by efficiently identifying athletes’ adaptation potentials.
Scoring the Future: Rethinking Prognostication in Acute-on-Chronic Liver Failure
Morphology of the glymphatic and meningeal lymphatic structures of the bottlenose dolphin
Declines and pronounced state-level variation in clozapine use among Medicare patients
Schizophrenia-spectrum disorders are debilitating and contribute to a substantial economic burden. Clinicians have historically underutilized clozapine, an atypical antipsychotic traditionally reserved for treatment-resistant schizophrenia, due to the medication’s adverse effect profile and associated management requirements, concerns of complications from poor treatment adherence, and inadequate training/exposure to its use. In addition to alleviating schizophrenia symptoms when multiple other medications have failed, clozapine has other areas of demonstrated effectiveness, such as reduced suicide ideation and action, aggression, substance use, and all-cause mortality benefits that compel its use. This study aimed to characterize clozapine utilization by United States (US) Medicare patients from 2015 to 2020. Additionally, we identified the states that prescribed significantly different amounts than the national average. We observed a steady decrease in clozapine use adjusted for population (−18.0%) and spending (−24.9%) over time. For all years, there was pronounced geographic heterogeneity (average: nine-fold) in population-corrected clozapine use. Massachusetts (2015−20: 95.4, 82.7, 76.8, 72.2, 71.2, 63.7 prescriptions per thousand enrollees) and South Dakota (2015−20: 78.0, 77.4, 78.4, 75.6, 72.0, 71.6) were the only states that prescribed significantly more than average, and none prescribed significantly less. Clozapine use by US Medicare patients is low, decreasing, and concerning for underutilization—patterns previously identified for US Medicaid recipients. Further study of the reasons for the pronounced state variation is needed. Education interventions, training reform, and devices that ease required routine blood monitoring are all practical solutions to optimize clozapine use.