A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder.

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Deliberate self-harm among pediatric psychiatric inpatients in China: A single-center retrospective study.

BACKGROUND: For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China. AIM: To understand the situation of DSH among hospitalized children and adolescents and its related factors. METHODS: In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH. RESULTS: A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting (n = 115, 48.12%) was the most common type of DSH. Females (n = 171, 71.55%) were more likely to engage in DSH than males (n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse. CONCLUSION: Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH.

[Contamination and Potential Ecological Risk Assessment of Heavy Metals in the Sediments of Yilong Lake, Southwest China].

The concentrations of Al, Ti, As, Cd, Cr, Cu, Ni, Pb, Zn, and Hg and chemical speciation of Cd, Cr, Cu, Ni, Pb, and Zn in four short cores sampled from the Yilong Lake, Yunnan Province were analyzed. The vertical and spatial features in the pollution levels and potential ecological risks of heavy metals in the sediments were studied. Except for the wide concentration ranges of Cd, the metals in the sediments showed narrow variations in their concentrations with coefficients of variation less than 0.3. According to the cluster analysis results, all metals could be classified into two groups:metals in group Ⅰ included As, Cd, Hg, and Pb, while metals in group Ⅱ included Al, Ti, Cr, Cu, Ni, and Zn. The metals in each group exhibited similar vertical variations in each core, but their variations were highly different between the cores. The correlation analysis results demonstrated that the variations in metal concentrations in the sediments were greatly regulated by the sediment texture. Therefore, the enrichment factor (EF) method was used for the differentiation of metals from the natural and anthropogenic sources and for the pollution assessment based on the total metal concentrations. The Cd and Pb in the sediments were mainly presented in the reducible speciation with percentages of 48% and 42%, respectively; Cr, Cu, Zn, and Ni were primarily (68%-82%) associated with the residual speciation. Based on the EF and chemical speciation of metals and their enrichment coefficients of the secondary phase, Cd was the typical pollutant with moderate pollution on average, and the other elements were observed in non-to weak pollution levels. Anthropogenic metals were mainly associated with the extractable speciation in the sediment. Combining the ecological risk index, the sediment quality guidelines, as well as the pollution level and chemical speciation of metals, As, Cu, Hg, Ni, Pb, and Zn in the surface sediments of Yilong Lake should have low potential ecological risk. However, Cd may pose a high potential ecological risk.

N-Bromosuccinimide-Induced C-H Bond Functionalization: An Intramolecular Cycloaromatization of Electron Withdrawing Group Substituted 1-Biphenyl-2-ylethanone for the Synthesis of 10-Phenanthrenol.

An NBS-induced intramolecular cycloaromatization for the synthesis of 10-phenanthrenols from electron-withdrawing group substituted 1-biphenyl-2-ylethanones is described. The in situ generated bromide was designed to act as an initiator for the radical C-H bond activation. An oxidative cross-dehydrogenative coupling reaction of a highly active C-H bond with an inert C-H bond readily occurs under mild conditions without the need for transition metals or strong oxidants.

A model to predict the onset of non-alcoholic fatty liver disease within 2 years in elderly adults.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. However, it is difficult to identify subjects at high risk for NAFLD onset. This study aims to construct a model to predict the onset of NAFLD within 2 years in elderly adults. METHODS: This study included and followed 3378 initial NAFLD-free subjects aged 60 years or over for 2 years, which were randomly divided into a training set and a validation set. NAFLD was diagnosed on ultrasound. Clinical and laboratory data were recorded at baseline. A model was constructed in the training set to predict the onset of NAFLD and validated in the validation set. RESULTS: Body mass index, hemoglobin, fasting blood glucose, and triglycerides were identified as predictors for the onset of NAFLD. A risk score (R) was calculated by them. It classified the subjects into low-risk group (R ≤ -2.88), moderate-risk group (-2.88 < R ≤ -1.26), and high-risk group (R > -1.26). In the training set, 4.68% of the participants in the low-risk group, 11.59% of the participants in the moderate-risk group, and 31.02% of the participants in the high-risk group developed NAFLD. In the validation set, 5.84% of the participants in the low-risk group, 10.57% of the participants in the moderate-risk group, and 29.44% of the participants in the high-risk group developed NAFLD. CONCLUSIONS: This study developed a model to predict the onset of NAFLD in elderly adults, which might provide indications for intervention to these subjects.

[Spatio-temporal Variations, Contamination and Potential Ecological Risk of Heavy Metals in the Sediments of Chenghai Lake].

Heavy metals pollution in the sediments is one of the main factors impacting the water quality and ecosystem health. In this study, concentrations of ten metals in nine sediment cores from the Chenghai Lake were determined. Chronology of a typical core (CH2012) was constructed by the 210Pb and 137Cs dating method. The spatio-temporal variations in concentrations and contamination characteristics of As, Cd, Cu, Hg, Ni, Pb, and Zn were evaluated. The potential eco-risks of heavy metals in the surface sediments were studied by combining the ecological risk index and sediment quality guidelines (SQGs) assessment as well as their pollution levels (enrichment factors, EF). The metal concentrations in each sediment core showed little vertical change with coefficients of variation of less than 0.20, except for Cd, whose coefficient of variation was 0.59. Spatially, the average concentrations of each metal showed minor difference among the cores, with ratios ranging from 1.2 to 1.8, suggesting similar sedimentary characteristics of metals in the whole lake. Cd and Pb were influenced by anthropogenic contamination that has started in the mid-1980s. The pollution level of Cd decreased in the past decade and still belongs to the moderate pollution degree, whereas the pollution level of Pb increased continually and could be classified as the weak pollution degree. The Hg contamination began in the late 1990s, with EFs ranging from 0.9 to 1.6, belonging to the weak pollution degree. The As, Cu, and Zn pollution occurred mainly near the surface sediments with weak pollution degrees. Spatially, there were no obvious trends in pollution levels of the metals. The heavy metals pollution is mainly influenced by atmospheric deposition that originates from non-ferrous metal smelting emissions, as well as agricultural and domestic discharges. As, Cu, Ni, Pb, and Zn in the surface sediments have low potential ecological risks, whereas Hg and Cd may pose middle-high potential risks.

Salicylic acid enhances Jaceosidin and Syringin production in cell cultures of Saussurea medusa.

Addition of 20 muM salicylic acid to Saussurea medusa cell cultures at day 6 resulted in jaceosidin and syringin productions up to 95 mg l(-1 )and 631 mg l(-1) which were, respectively, about 2.5- and 2.7-fold higher than in the control. The biomass was increased from 8 to 12 g l(-1). Expression of chalcone synthase gene (chs) increased sharply after 12 h treatment and was sustained up to 48 h; chalcone isomerase gene (chi) expression reached a peak at 24 h and decreased after 48 h; and phenylalanine ammonia-lyase activity increased by 7.5-fold (96 U mg(-1) protein) higher than in the control after 24 h. These results indicate that salicylic acid enhances the production of jaceosidin and syringin which is accompanied by induction of the related phenylpropanoid biosynthetic enzymes.