ASIC1a regulates ferroptosis in hepatic stellate cells via the Hippo/Yap-1 pathway in liver fibrosis.

BACKGROUND: Liver fibrosis is a sustained process of liver tissue damage and repair caused by various physiological and pathological factors, with the activation and proliferation of hepatic stellate cells being central. Therefore, understanding and clarifying the relevant mechanisms of hepatic stellate cell activation and death is of great clinical significance for the treatment of liver fibrosis diseases. METHODS: In vivo, recombinant adeno-associated virus was used to infect the liver of experimental mice, overexpressing ASIC1a, and based on this, a liver fibrosis model treated with sorafenib was constructed. In vitro, using RNA plasmid technology to transfect HSC-T6 cells, ASIC1a was overexpressed or silenced in the cells, and on this basis, PDGF-BB and Sorafenib were used to stimulate HSC-T6 cells, causing activated HSC-T6 to undergo ferroptosis. RESULTS: The ferroptosis inducers Sorafenib and erastin can induce ferroptosis in HSCs, effectively inhibiting or reversing the progression of liver fibrosis. We found that the expression level of ASIC1a was significantly reduced in the livers of mice with liver fibrosis treated with Sorafenib. After treatment with an adeno-associated virus overexpressing ASIC1a, the therapeutic effect of Sorafenib was inhibited, and the level of ferroptosis induced by Sorafenib was also inhibited. The induction of ferroptosis in hepatic stellate cells in vitro depends on the presence of ASIC1a. By further exploring the potential mechanism, we observed that the overexpression of ASIC1a can promote an increase in YAP nuclear translocation, thereby regulating the activity of Hippo/YAP pathway signaling. After treatment with Sorafenib, the influx of Ca2+ significantly increased when ASIC1a was overexpressed, and BAPTA-AM intervention eliminated the intracellular Ca2+ accumulation induced by ASIC1a overexpression. CONCLUSIONS: This indicated that the activation of YAP depends on the calcium ion influx induced by ASIC1a, which regulates ferroptosis in hepatic stellate cells by regulating the calcium ion-dependent Hippo/YAP pathway.

The Protective Effect of Octanoic Acid on Sepsis: A Review.

Sepsis, a systemic inflammation that occurs in response to a bacterial infection, is a significant medical challenge. Research conducted over the past decade has indicated strong associations among a patient's nutritional status, the composition of their gut microbiome, and the risk, severity, and prognosis of sepsis. Octanoic acid (OA) plays a vital role in combating sepsis and has a protective effect on both animal models and human patients. In this discussion, the potential protective mechanisms of OA in sepsis, focusing on its regulation of the inflammatory response, immune system, oxidative stress, gastrointestinal microbiome and barrier function, metabolic disorders and malnutrition, as well as organ dysfunction are explored. A comprehensive understanding of the mechanisms by which OA act may pave the way for new preventive and therapeutic approaches to sepsis.

Low muscle mass-to-fat ratio is an independent factor that predicts worse overall survival and complications in patients with colon cancer: a retrospective single-center cohort study.

Purpose: This study was performed to investigate influencing factors of preoperative muscle mass-to-fat ratio (MMFR) and its impact on overall survival and postoperative complications of colon cancer. Methods: Patients who underwent colectomy for stage I-III colon cancer at the Second Affiliated Hospital of Soochow University between January 2016 and December 2022 were included. The skeletal muscle and fat area at the third lumbar vertebra were measured with preoperative CT measurement. MMFR was defined as the ratio of skeletal muscle area to total fat area, and low MMFR was defined as the 2 lowest tertiles (≤0.585). Univariate and multivariable analyses were conducted to assess the impact of MMFR on overall complications and survival outcomes. Kaplan-Meier survival curves and log-rank test were used to compare the overall survival between high MMFR and low MMFR groups. Results: A total of 885 patients were analyzed. Female sex, older age, high body mass index, sarcopenia, and high cancer stage were more likely to result in low MMFR. Complications, including intestinal fistula, chylous fistula and organ space surgical site infection were significantly higher in the low MMFR group. Low MMFR was an independent factor associated with overall complications (odds ratio, 1.940; 95% confidence interval [CI], 1.252-3.007; P < 0.01) and long-term survival (hazard ratio, 2.222; 95% CI, 1.443-3.425; P < 0.01). Furthermore, patients with high MMFR had a higher survival rate than patients with low MMFR (P < 0.01). Conclusion: Low MMFR is an independent factor that predicts worse overall survival and complications in patients with colon cancer.

Temporal variations in absorption and translocation of heavy metal(loid)s in pak choi (Brassica rapa L.) under open-field and greenhouse cultivation.

Elucidating the absorption and translocation of heavy metal(loid)s by common vegetables across different growth environments and stages is crucial for conducting accurate environmental risk assessments and for associated control. This study investigated temporal variations in the absorption and translocation capacities of pak choi (Brassica rapa L.) for As, Cd, Cr, Cu, Pb, and Zn in polluted soils during the plant growth cycle under greenhouse and open-field cultivation modes. Results showed high root metal(loid) bioconcentration factors and root-to-shoot translocation factors for Cd (0.25 and 1.44, respectively) and Zn (0.26 and 1.01), but low values for As (0.06 and 0.88) and Pb (0.06 and 0.87). The Cd concentration in the aerial edible parts peaked during the early slow growth period, whereas other heavy metal(loid)s peaked during the later stable maturity period. Root bioconcentration and root-to-shoot translocation factors did not significantly differ between cultivation modes. However, greenhouse cultivation exhibited lower average Cd and Zn concentrations in the edible parts and cumulative uptake amounts of most metal(loid)s than open-field cultivation during the typical harvest period spanning days 60 and 90. Short-term transitioning from open-field to greenhouse cultivation may reduce health risks associated with heavy metal(loid) intake via pak choi consumption. These findings facilitate sustainable agricultural practices and food safety management.

Understanding COVID-19-Related Behaviors, Worries, and Attitudes among Chinese: Roles of Personality and Severity.

During the COVID-19 pandemic, people exhibited various forms of adjustments. This study examines how situational factors (i.e., the severity of COVID-19) and individual differences (i.e., the HEXACO traits) affect one's COVID-19-related responses regarding behaviors (i.e., mask-wearing and hoarding), worries (i.e., worrying about infecting and spreading COVID-19), and attitudes (i.e., discrimination and empathy toward people infecting COVID-19) in China. With a sample of 927 participants, our results show that the severity of COVID-19 was predictive of all the responses, and its predictive value was more pronounced relative to personality traits. Concerning the association between personality traits and responses, Honesty-Humility and Conscientiousness were predictive of one's behaviors, Emotionality was predictive of one's worries, and almost all the HEXACO traits were associated with one's attitudes toward people infected with COVID-19. This study sheds some light on understanding how situations and individual differences shape one's responses in a time of emergency.

A review on the advancement in photocatalytic degradation of poly/perfluoroalkyl substances in water: Insights into the mechanisms and structure-function relationship.

Poly/perfluoroalkyl substances (PFAS) are persistent organic pollutants and ubiquitous in aquatic environment, which are hazardous to organisms and human health. Several countries and regions have taken actions to regulate or limit the production and emission of some PFAS. Even though a series of water treatment technologies have been developed for removal of PFAS to eliminate their potential adverse effects, the removal and degradation performance are usually unsatisfactory. Photocatalytic degradation of PFAS is considered as one of the most effective approaches due to the mild operation conditions and environmental friendliness. This review systematically summarized the recent advances in photocatalytic degradation of PFAS based on heterogeneous photocatalysts, including TiO2-, Ga2O3-, In2O3-, ZnO-, Bi-based, and others. Overall, two mainly degradation mechanisms were involved, including photo-oxidation (involving the holes and oxidative radicals) and photo-reduction types (by e- and reductive radicals). The band structures of the photocatalysts, degradation pathways, structure-function relationship, and impacting factors were further discussed to elucidate the essential reasons for the enhanced degradation of PFAS. Furthermore, the review identified the major knowledge gaps to solve the issues of photocatalysis in real application. This paper also propounded several strategies to promote the design and optimization of high-efficient photocatalysts, and meet the challenges to remove PFAS through photodegradation technologies.

[Spatiotemporal Response of Ecosystem Service Value to Land Use Change in the Lanzhou-Xining Urban Agglomeration over the Past 20 Years].

With rapid urbanization and human activities exacerbating threats to the degradation of various ecosystem services in modern urban agglomerations, the exploration of the state of ecological security at the scale of urban agglomerations is of great significance. This study considered the Lanzhou-Xining Urban Agglomeration as the research area, based on the land use data in 2000, 2005, 2010, 2015, and 2020. At the same time, the landscape ecological risk index was introduced. The land use change characteristics of the Lanzhou-Xining Urban Agglomeration were analyzed by using the land use transfer matrix, the value per unit area equivalent factor method, and the bivariate spatial autocorrelation analysis method to elucidate the impacts of the changes in the ecological risk index induced by the land use transition on the value of ecosystem services. This study analyzed the land use change characteristics of the Lanzhou-Xining Urban Agglomeration and elucidated the impacts of changes in the ecological risk index on the value of ecosystem services caused by land use transformation. The results showed that:① During the period from 2000 to 2020, the land use types of the Lanzhou-Xining Urban Agglomeration were mainly dominated by grassland, cropland, and forest land. The construction land area had expanded significantly mainly from cropland and grassland, and the six land use types had strong cross-transformation. The total area of land use change was 6 646.05 km2. ② In terms of spatial changes, the spatial pattern of ecosystem service value in the Lanzhou-Xining Urban Agglomeration had not undergone obvious transformation. However, the regional variability was significant, generally showing the distribution characteristics of high in the northwest and low in the southeast. ③From the perspective of temporal change, the value of ecosystem services in the Lanzhou-Xining Urban Agglomeration showed an upward trend, with the total flow of value increasing from 186.459 billion yuan to 192.156 billion yuan, with a total value-added of 5.697 billion yuan. ④ There was a rising trend in the overall ecological risk index of the Lanzhou-Xining Urban Agglomeration over the past 20 years. Low ecological risk areas and lower ecological risk areas dominated the ecological risk areas. There was a significant positive correlation between the value of ecosystem services and the ecological risk index. This study aimed to reveal the understanding of the impacts of land-use practices on ecosystem service values and ecological risks, to provide important references for regional ecological risk management and land-use policy formulation, and thus to promote the high-quality development of the ecological environment in the Yellow River Basin.

Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy.

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

p85α deficiency alleviates ischemia-reperfusion injury by promoting cardiomyocyte survival.

Myocardial ischemia-reperfusion (I/R) injury is a prevalent cause of myocardial injury, involving a series of interconnected pathophysiological processes. However, there is currently no clinical therapy for effectively mitigating myocardial I/R injury. Here, we show that p85α protein levels increase in response to I/R injury through a comprehensive analysis of cardiac proteomics, and confirm this in the I/R-injured murine heart and failing human myocardium. Genetic inhibition of p85α in mice activates the Akt-GSK3ß/Bcl-x(L) signaling pathway and ameliorates I/R-induced cardiac dysfunction, apoptosis, inflammation, and mitochondrial dysfunction. p85α silencing in cardiomyocytes alleviates hypoxia-reoxygenation (H/R) injury through activating the Akt-GSK3ß/Bcl-x(L) signaling pathway, while its overexpression exacerbates the damage. Mechanistically, the interaction between MG53 and p85α triggers the ubiquitination and degradation of p85α, consequently enhancing Akt phosphorylation and ultimately having cardioprotective effects. Collectively, our findings reveal that substantial reduction of p85α and subsequently activated Akt signaling have a protective effect against cardiac I/R injury, representing an important therapeutic strategy for mitigating myocardial damage.

Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.