Association between plasma metal exposure and health span in very elderly adults: a prospective cohort study with mixture statistical approach.

BACKGROUND: Metals have been linked to a diverse spectrum of age-related diseases; however, the effects of metal exposure on health span remains largely unknown. This cohort study aims to determine the association between plasma metal and health span in elder adults aged ≥ 90 years. METHODS: The plasma concentrations of seven metals were measured at baseline in 300 elder adults. The end of the health span (EHS) was identified as the occurrence of one of eight major morbidities or mortality events. We used Cox regression to assess hazard ratios (HR). The combined effects of multiple metal mixtures were estimated using grouped-weighted quantile sum (GWQS), quantile g-computation (Q-gcomp), and Bayesian kernel machine regression (BKMR) methods. RESULTS: The estimated HR for EHS with an inter-quartile range (IQR) increment for selenium (Se) was 0.826 (95% confidence interval [CI]: 0.737-0.926); magnesium (Mg), 0.806 (95% CI: 0.691-0.941); iron (Fe), 0.756 (95% CI: 0.623-0.917), and copper (Cu), 0.856 (95% CI: 0.750-0.976). The P for trend of Se, Mg, and Fe were all < 0.05. In the mixture analyses, Q-gcomp showed a negative correlation with EHS (P = 0.904), with the sum of the negative coefficients being -0.211. CONCLUSION: Higher plasma Se, Mg, and Fe reduced the risk of premature end of health span, suggesting that essential metal elements played a role in health maintenance in elder adults.

Stress response membrane protein OsSMP2 negatively regulates rice tolerance to drought.

In a gene chip analysis, rice (Oryza sativa) OsSMP2 gene expression was induced under various abiotic stresses, prompting an investigation into its role in drought resistance and abscisic acid signaling. Subsequent experiments, including qRT-PCR and ß-glucuronidase activity detection, affirmed the OsSMP2 gene's predominant induction by drought stress. Subcellular localization experiments indicated the OsSMP2 protein primarily localizes to the cell membrane system. Overexpressing OsSMP2 increased sensitivity to exogenous abscisic acid, reducing drought resistance and leading to reactive oxygen species accumulation under drought stress. Conversely, in simulated drought experiments, OsSMP2-silenced transgenic plants showed significantly longer roots compared with the wild-type Nipponbare. These results suggest that OsSMP2 overexpression negatively affects rice drought resistance, offering valuable insights into molecular mechanisms, and highlight OsSMP2 as a potential target for enhancing crop resilience to drought stress.

Association and mediation between educational attainment and respiratory diseases: a Mendelian randomization study.

BACKGROUND: Respiratory diseases are a major health burden, and educational inequalities may influence disease prevalence. We aim to evaluate the causal link between educational attainment and respiratory disease, and to determine the mediating influence of several known modifiable risk factors. METHODS: We conducted a two-step, two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) and single nucleotide polymorphisms (SNPs) as instrumental variables for educational attainment and respiratory diseases. Additionally, we performed a multivariable MR analysis to estimate the direct causal effect of each exposure variable included in the analysis on the outcome, conditional on the other exposure variables included in the model. The mediating roles of body mass index (BMI), physical activity, and smoking were also assessed. FINDINGS: MR analyses provide evidence of genetically predicted educational attainment on the risk of FEV1 (ß = 0.10, 95% CI 0.06, 0.14), FVC (ß = 0.12, 95% CI 0.07, 0.16), FEV1/FVC (ß = - 0.005, 95% CI - 0.05, 0.04), lung cancer (OR = 0.54, 95% CI 0.45, 0.65) and asthma (OR = 0.86, 95% CI 0.78, 0.94). Multivariable MR dicated the effect of educational attainment on FEV1 (ß = 0.10, 95% CI 0.04, 0.16), FVC (ß = 0.07, 95% CI 0.01, 0.12), FEV1/FVC (ß = 0.07, 95% CI 0.01, 0.01), lung cancer (OR = 0.55, 95% CI 0.42, 0.71) and asthma (OR = 0.88, 95% CI 0.78, 0.99) persisted after adjusting BMI and cigarettes per day. Of the 23 potential risk factors, BMI, smoking may partially mediate the relationship between education and lung disease. CONCLUSION: High levels of educational attainment have a potential causal protective effect on respiratory diseases. Reducing smoking and adiposity may be a target for the prevention of respiratory diseases attributable to low educational attainment.

Selenium in rice: Impact on protein content and distribution for enhanced food and feed security in agroclimatic challenges.

Countries face exasperating and inclement climate worldwide. Food and feed security could be their paramount life objective. The study aimed to investigate the impact of selenium on the protein content and distribution in different parts of rice. For this purpose, advanced selenium biofortified breeding material developed after generations of breeding efforts was investigated at the field area, rice research institute, Chengdu, China during cropping season 2021-22. The accumulation and distribution of selenium and protein contents were observed in various fractions of selenium-enriched rice (Z3057B) and positive control (727). The correlation studies for selenium and protein quantification leads to the optimization of the breeding material and relevance in virtue. The rice fractions indicated rice embryo retains highest selenium contents, which gradually decreases in succession (other rice parts). The difference in protein content between the embryo and endosperm of Se-enriched rice is significant, while that between embryo and aleurone layer is not obvious. The selenium protein was found with molecular weight of 13.6-122.6 kDa. The protein of each molecular weight is found to bind with selenium, but the binding strength of selenium is negatively correlated with the molecular weight of protein. The 67.5% of the total selenium sticks with protein having molecular weight less than 38.8 kDa. In summary, protein with low molecular weight (13.4 kDa) binds maximum selenium and accounts for highest total protein content (40.76%).

Biliary sepsis complication with congenital hepatic fibrosis: an unexpected outcome.

BACKGROUND: CHF (Congenital hepatic fibrosis) is a rare hereditary disease characterized by periportal fibrosis and ductal plate malformation. Little is known about the clinical presentations and outcome in CHF patients with an extraordinary complication with biliary sepsis. Our case described a 23-year-old female diagnosed as CHF combined with biliary sepsis. Her blood culture was positive for KP (Klebsiella pneumoniae), and with a high level of CA19-9 (> 1200.00 U/ml, ref: <37.00 U/ml). Meanwhile, her imaging examinations showed intrahepatic bile duct dilatation, portal hypertension, splenomegaly, and renal cysts. Liver pathology revealed periportal fibrosis and irregularly shaped proliferating bile ducts. Whole-exome sequencing identified two heterozygous missense variants c.3860T > G (p. V1287G) and c.9059T > C (p. L3020P) in PKHD1 gene. After biliary sepsis relieved, her liver function test was normal, and imaging examination results showed no significant difference with the results harvested during her biliary sepsis occurred. CONCLUSION: The diagnosis of CHF complicated with biliary sepsis in the patient was made. Severely biliary sepsis due to KP infection may not inevitably aggravate congential liver abnormality in young patients. Our case provides a good reference for timely treatment of CHF patients with biliary sepsis.

AP2/EREBP Pathway Plays an Important Role in Chaling Wild Rice Tolerance to Cold Stress.

Cold stress is the main factor limiting rice production and distribution. Chaling wild rice can survive in cold winters. AP2/EREBP is a known transcription factor family associated with abiotic stress. We identified the members of the AP2/EREBP transcription factor family in rice, maize, and Arabidopsis, and conducted collinearity analysis and gene family analysis. We used Affymetrix array technology to analyze the expression of AP2/EREBP family genes in Chaling wild rice and cultivated rice cultivar Pei'ai64S, which is sensitive to cold. According to the GeneChip results, the expression levels of AP2/EREBP genes in Chaling wild rice were different from those in Pei'ai64S; and the increase rate of 36 AP2/EREBP genes in Chaling wild rice was higher than that in Pei'ai64S. Meanwhile, the MYC elements in cultivated rice and Chaling wild rice for the Os01g49830, Os03g08470, and Os03g64260 genes had different promoter sequences, resulting in the high expression of these genes in Chaling wild rice under low-temperature conditions. Furthermore, we analyzed the upstream and downstream genes of the AP2/EREBP transcription factor family and studied the conservation of these genes. We found that the upstream transcription factors were more conserved, indicating that these upstream transcription factors may be more important in regulating cold stress. Meanwhile, we found the expression of AP2/EREBP pathway genes was significantly increased in recombinant inbred lines from Nipponbare crossing with Chaling wild rice, These results suggest that the AP2/EREBP signaling pathway plays an important role in Chaling wild rice tolerance to cold stress.

The risk of suicidal intention in severe mental illness: An ecological perspective.

OBJECTIVE: Guided by the ecosystem theory model framework, we aimed to explore the influence of three ecological dimensions (social, family and psychological factors) on suicidal intention in people with severe mental illness (SMI). We hypothesized that three factors influence suicidal intention, and that psychological factors may play a mediating role in the influence of social and family factors on suicidal intention. METHODS: We collected 994 patients with SMI aged 18 and above from May 2021 to March 2022 in the Fourth Hospital of Fuzhou City. We used logistic regression to analyse the association between social, family, psychological factors and suicidal intention. Furthermore, we explored the mediating effects among the influencing factors. RESULTS: Younger male patients with schizophrenia were more likely to have suicidal intention due to psychosocial family factors (p < .05). Social factors (poor interpersonal relations, social retreat, social activities outside the home), family factors (parental functions, activities within the family, family functions), psychological factors (anxiety, depression, interest in the outside world, overt aggression, lack of accountability and planning) were all independent risk factors for suicidal intention in patients. Mediation analysis showed anxiety and depression mediated the role of social and family factors on suicidal intention (p < .05). CONCLUSION: Social, family and psychological factors were important risk factors for suicidal intention, with anxiety and depression being partial mediators for suicidal intention. Therefore, interventions that enhance family and social functioning and reduce anxiety and depression may be effective in reducing suicidal intention in SMI.

Association of ambient PM10 and PM2.5 with coronary stenosis measured using selective coronary angiography.

BACKGROUND: Long-term ambient particulate matter (PM) exposure exerts detrimental effects on cardiovascular health. Evidence on the relation of chronically exposed ambient PM10 and PM2.5 with coronary stenosis remains lacking. Our aim was to investigate the association of PM10 and PM2.5 with coronary stenosis in patients undergoing coronary angiography. METHODS: We performed a retrospective cohort study consisting of 7513 individuals who underwent coronary angiography in Fujian Province, China, from January 2019 to December 2021. We calculated a modified Gensini score (GS) to represent the degree of stenosis in coronary arteries by selective coronary angiography. We fitted linear regressions and logistic models to assess the association of PM10 and PM2.5 with coronary stenosis. We employed restricted cubic splines to describe the exposure-response curves. We performed mediation analyses to assess the potential mediators. RESULTS: Long-term ambient PM10 and PM2.5 (prior three years average) exposure was significantly associated with the GS, with a breakpoint concentration of 47.5 µg/m3 and 25.8 µg/m3 for PM10 and PM2.5, respectively, above which we found a linear positive exposure-response relationship of ambient PM with GS. Each 10 µg /m3 increase in PM10 exposure (ß: 4.81, 95 % CI: 0.44-9.19) and PM2.5 exposure [ß: 10.50, 95 % CI: 3.14-17.86] were positively related to the GS. The adjusted odds ratio (OR) for each 10 µg/m3 increment in PM10 exposure on severe coronary stenosis was 1.33 (95 % CI: 1.04-1.76). Correspondingly, the adjusted OR for PM2.5 was 1.87 (95 % CI: 1.24-2.99). The mediation analysis indicated that the effect of PM10 on coronary stenosis may be partially mediated through total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, serum creatinine and blood urea nitrogen, and the effect of PM2.5 may be mediated in part by hemoglobin A1c. CONCLUSION: Our study provides the first evidence that chronic ambient PM10 and PM2.5 exposure was associated with coronary stenosis assessed by GS in patients with suspected coronary artery disease and reveals its potential mediators.

Associated Outcomes of Different Intravenous Antibiotics Combined with 2% Mupirocin Ointment in the Treatment of Pediatric Patients with Staphylococcal Scalded Skin Syndrome.

Purpose: To compare treatment duration, influencing factors, and costs among intravenous antibiotic groups combined with 2% mupirocin ointment for treating staphylococcal scalded skin syndrome (SSSS). Patients and Methods: Sex, age, onset days before admission, febrile status, white blood cell (WBC) count, and C-reactive protein (CRP) level were recorded as baseline characteristics for 253 included patients. The antibiotic sensitivity results were statistically compared by Cochran's Q test. Kruskal-Wallis tests were used to compare days and the total costs of hospitalization with different intravenous antibiotic applications. Mann-Whitney U-tests or Spearman's rank correlation tests were used for the univariate analysis. Finally, a multivariate linear regression model was employed to determine the variables with statistical significance. Results: The sensitivity rates of oxacillin (84.62%), vancomycin (100%), and mupirocin (100%) were significantly higher than those of clindamycin (7.69%) (p<0.0001). The duration of intravenous ceftriaxone administration was significantly longer than that of amoxicillin-clavulanic acid, cefathiamidine, and cefuroxime (p<0.01). The total hospitalization costs for cefathiamidine were significantly higher than those for amoxicillin-clavulanic acid and cefuroxime (p<0.05). According to the multiple linear regression, ages ≥60 months old were correlated with shorter treatment duration (ß=-1.48, [95% CI: -2.29, -0.66] for amoxicillin-clavulanic acid, and ß=-1.44, [95% CI: -2.06, -0.83] for cefathiamidine, and ß=-0.96, [95% CI: -1.58, -0.34] for cefuroxime) (all p<0.01). In multivariate analysis for cefathiamidine, higher WBC count (ß=0.05, [95% CI: 0.01, 0.10], p<0.05) and CRP level (ß=1.12, [95% CI: 0.14, 2.10], p<0.05) were associated with longer treatment course. Conclusion: Oxacillin resistance was rare, and clindamycin resistance was high in pediatric patients with SSSS in our district. Intravenous amoxicillin-clavulanic acid and cefuroxime combined with topical mupirocin were favorable due to a shorter intravenous treatment course and lower costs. Younger age, elevated WBC count, and CRP levels could indicate a longer course of treatment with intravenous antibiotics.

The Effect of Amoxicillin Pre-Exposure on Treatment Outcomes and Antimicrobial Susceptibility in Patients with Urogenital Chlamydia trachomatis Infection.

Purpose: We investigated the influence of amoxicillin pre-exposure on treatment outcomes, Chlamydia trachomatis (CT) culture, the presence of drug-resistant genes, minimum inhibitory concentrations (MICs), and fractional inhibitory concentrations (FICs) in CT clinical strains. Additionally, we explored the effect of different antimicrobial combinations on CT. Patients and Methods: Clinical data of 62 patients with CT infection were recorded. Of these, 33 had pre-exposure to amoxicillin and 29 did not. Among patients with pre-exposure, 17 received azithromycin and 16 received minocycline. Among the patients without pre-exposure, 15 received azithromycin and 14 received minocycline. All patients underwent microbiological cure follow-ups one month after completing the treatment. 23S rRNA gene mutations, acquisition of tet(M) and tet(C) were detected using reverse transcription PCR (RT-PCR) and PCR, respectively. The MICs and FICs of azithromycin, minocycline, and moxifloxacin, alone or in combination, were determined using the microdilution and checkerboard methods, respectively. Results: More cases of treatment failure occurred in pre-exposed patients, in both treatment groups (P <0.05). No 23S rRNA gene mutations or tet(M) and tet(C) acquisitions were found. More inclusion bodies were cultured from patients without amoxicillin pre-exposure than from those with pre-exposure (P <0.0001). The MICs of all antibiotics were higher in pre-exposed patients than in those without pre-exposure (P <0.01). The FICs of azithromycin plus moxifloxacin were lower than those of the other antibiotic combinations (P <0.0001). The synergy rate of azithromycin plus moxifloxacin was significantly higher than those of azithromycin plus minocycline and minocycline plus moxifloxacin (P <0.001). The FICs of all antibiotic combinations were comparable between isolates from the two patient groups (all P >0.05). Conclusion: Pre-exposure to amoxicillin in CT patients may inhibit CT growth and decrease sensitivity of CT strains to antibiotics. Azithromycin plus moxifloxacin may be a promising treatment regimen for genital CT infections with treatment failure.

Culture conditions of mouse ESCs impact the tumor appearance in vivo.

Various culture conditions by small molecules have been explored to extend pluripotency of stem cells, but their impacts on cell fate in vivo remain elusive. We systematically compared the effects of various culture conditions on the pluripotency and cell fate in vivo of mouse embryonic stem cells (ESCs) by tetraploid embryo complementation assay. Conventional ESC cultures in serum/LIF-based condition produced complete ESC mice and also the survival to adulthood at the highest rates of all other chemical-based cultures. Moreover, long-term examination of the survived ESC mice demonstrated that conventional ESC cultures did not lead to visible abnormality for up to 1.5-2 years, whereas the prolonged chemical-based cultures developed retroperitoneal atypical teratomas or leiomyomas. The chemical-based cultures exhibited transcriptomes and epigenomes that typically differed from those of conventional ESC cultures. Our results warrant further refinement of culture conditions in promoting the pluripotency and safety of ESCs in future applications.

Ectopic Expression of a Maize Gene ZmDUF1645 in Rice Increases Grain Length and Yield, but Reduces Drought Stress Tolerance.

As the human population grows rapidly, food shortages will become an even greater problem; therefore, increasing crop yield has become a focus of rice breeding programs. The maize gene, ZmDUF1645, encoding a putative member of the DUF1645 protein family with an unknown function, was transformed into rice. Phenotypic analysis showed that enhanced ZmDUF1645 expression significantly altered various traits in transgenic rice plants, including increased grain length, width, weight, and number per panicle, resulting in a significant increase in yield, but a decrease in rice tolerance to drought stress. qRT-PCR results showed that the expression of the related genes regulating meristem activity, such as MPKA, CDKA, a novel crop grain filling gene (GIF1), and GS3, was significantly changed in the ZmDUF1645-overexpression lines. Subcellular colocalization showed that ZmDUF1645 was primarily localized on cell membrane systems. Based on these findings, we speculate that ZmDUF1645, like the OsSGL gene in the same protein family, may regulate grain size and affect yield through the cytokinin signaling pathway. This research provides further knowledge and understanding of the unknown functions of the DUF1645 protein family and may serve as a reference for biological breeding engineering to increase maize crop yield.

Solitary Interdigital Condyloma Latum in a Female Adolescent: A Case Report of an Unusual Form of Secondary Syphilis.

Condylomata lata are flat-topped, moist papules or plaques usually found in the anogenital area as cutaneous manifestations of secondary syphilis. Here, we present a unique case of a solitary interdigital condyloma latum of secondary syphilis in a 16-year-old female sex worker without other cutaneous findings. Sexual contact history, histopathology, including direct detection of Treponema pallidum, and serological tests were essential for the diagnosis of this case. The patient reached serological cure with two doses of intramuscularly delivered penicillin G benzathine. Owing to the dramatic rise in the incidence of primary and secondary syphilis, medical workers should be aware of the atypical skin manifestations of secondary syphilis in adolescents who are at risk of acquiring sexually transmitted diseases to avoid the progression to late syphilis and further transmission to sexual partners.

PROS1 variant c.1574C>T p.Ala525Val causes portal vein thrombosis with protein S deficiency.

BACKGROUND: Protein S (PS) is a vitamin K-dependent plasma glycoprotein, and the deficiency of PS increases the risk of venous thromboembolism (VTE). PS deficiency has been found in 1.5-7% of selected groups of thrombophilic patients. However, the reported PS deficiency patients with portal vein thrombosis are scarce. CASE REPORT AND RESULTS: Our case described a 60-year-old male patient presented portal vein thrombosis with protein S deficiency. Imaging findings of the patient revealed extensive thrombosis involving the portal vein and superior mesenteric vein. His medical history revealed lower extremity venous thrombosis 10 years ago. The level of PS activity was greatly reduced (14%, reference: 55-130%). Acquired thrombophilia caused by antiphospholipid syndrome, hyperhomocysteinemia, or malignancy were excluded. Whole exome sequencing revealed a heterozygous missense variation c.1574C>T, p.Ala525Val in the PROS1 gene. The in-silico analysis of the variant was performed by SIFT and PolyPhen-2. The results showed that the variant is a pathogenic and likely pathogenic variation respectively (SIFT, -3.404; PolyPhen-2, 0.892), the amino acid substitution A525V is presumed to result in unstable PS protein which is degraded intracellularly. Mutation site of the proband and his family members was validated by Sanger sequencing. CONCLUSION: According to the clinical manifestation, imaging findings, protein S level, and the genetic results, a diagnosis of portal vein thrombosis with PS deficiency was made. To the best of our knowledge, our case is the second reported PS deficiency patient caused by PROS1 c.1574C>T, p.Ala525Val variant in Asia, and the case is also the only reported case with PROS1 c.1574C>T, p.Ala525Val variant presents portal vein thrombosis.

Comparative Responses of Silicon to Reduce Cadmium and Enrich Selenium in Rice Varieties.

Cadmium (Cd), a highly toxic heavy metal for crops in China, poses a significant threat to rice cultivation. It is crucial to identify the genotypes with robust resistance to heavy metals, including Cd, in rice. The experiment was conducted to examine the mitigation effect of silicon (Si) on Cd toxicity levels in Se-enriched Z3055B and non-Se-enriched G46B rice genotypes. A basal dose of Si improved the growth and the quality of rice significantly by reducing the Cd content in rice roots, stems, leaves and grains and increased the yield, biomass and selenium (Se) content of brown rice in both genotypes. Additionally, Se content in brown rice and polished rice was notably higher in Se-enriched rice than in non-Se-enriched rice, with the highest amount at 0.129 mg/kg and 0.085 mg/kg, respectively. The results demonstrated that a basal fertilizer concentration of 30 mg/kg of Si was more effective in reducing Cd transport from roots to shoots in Se-enriched rice than in non-Se-enriched rice genotypes. Therefore, it can be concluded that Se-enriched rice genotypes are a viable option for food crop production in Cd-contaminated areas.

Generic User Behavior: A User Behavior Similarity-Based Recommendation Method.

Recommender system (RS) plays an important role in Big Data research. Its main idea is to handle huge amounts of data to accurately recommend items to users. The recommendation method is the core research content of the whole RS. However, the existing recommendation methods still have the following two shortcomings: (1) Most recommendation methods use only one kind of information about the user's interaction with items (such as Browse or Purchase), which makes it difficult to model complete user preference. (2) Most mainstream recommendation methods only consider the final consistency of recommendation (e.g., user preferences) but ignore the process consistency (e.g., user behavior), which leads to the biased final result. In this article, we propose a recommendation method based on the Entity Interaction Knowledge Graph (EIKG), which draws on the idea of collaborative filtering and innovatively uses the similarity of user behaviors to recommend items. The method first extracts fact triples containing interaction relations from relevant data sets to generate the EIKG; then embeds the entities and relations in the EIKG; finally, uses link prediction techniques to recommend items for users. The proposed method is compared with other recommendation methods on two publicly available data sets, Scholat and Lizhi, and the experimental result shows that it exceeds the state of the art in most metrics, verifying the effectiveness of the proposed method.

Hidrotic ectodermal dysplasia in a Chinese pedigree: A case report.

BACKGROUND: We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia (HED) with a variation in GJB6 (c.31G>A). The patients in the family had a triad of clinical manifestations of varying degrees. Although the same variation locus have been reported, the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder, palmoplantar keratosis, and congenital hypotrichosis. CASE SUMMARY: This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED. The proband (IV4) was a male patient with normal sweat gland function and dental development, no skeletal dysplasia, no cognitive disability, and no hearing impairments. His parents were not consanguineously married. Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longitudinal ridges, in addition to mild bilateral palmoplantar hyperkeratosis. GJB6, GJB2, and GJA1 have been reported to be the causative genes of HED; therefore, we subjected the patient's samples to Sanger sequencing of these three genes. In this family, the variation locus was at GJB6 (c.31G>A, p.Gly11Arg). Overexpression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models, and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot, respectively. CONCLUSION: We report another HED phenotype associated with GJB6 variations, which can help clinicians to diagnose HED despite its varying presentations.

Reprogramming of ovarian aging epigenome by resveratrol.

Resveratrol is an antiaging, antioxidant, and anti-inflammatory natural polyphenolic compound. Growing evidence indicates that resveratrol has potential therapeutic effects for improving aging ovarian function. However, the mechanisms underlying prolonged reproductive longevity remain elusive. We found that resveratrol ameliorates ovarian aging transcriptome, some of which are associated with specific changes in methylome. In addition to known aging transcriptome of oocytes and granulosa cells such as decline in oxidoreductase activity, metabolism and mitochondria function, and elevated DNA damage and apoptosis, actin cytoskeleton are notably downregulated with age, and these defects are mostly rescued by resveratrol. Moreover, the aging-associated hypermethylation of actin cytoskeleton is decreased by resveratrol. In contrast, deletion of Tet2, involved in DNA demethylation, abrogates resveratrol-reprogrammed ovarian aging transcriptome. Consistently, Tet2 deficiency results in additional altered pathways as shown by increased mTOR and Wnt signaling, as well as reduced DNA repair and actin cytoskeleton with mouse age. Moreover, genes associated with oxidoreductase activity and oxidation-reduction process were hypermethylated in Tet2-deficient oocytes from middle-age mice treated with resveratrol, indicating that loss of Tet2 abolishes the antioxidant effect of resveratrol. Taking together, our finding provides a comprehensive landscape of transcriptome and epigenetic changes associated with ovarian aging that can be reprogrammed by resveratrol administration, and suggests that aberrantly increased DNA methylation by Tet2 deficiency promotes additional aging epigenome that cannot be effectively restored to younger state by resveratrol.

Association between solid cooking fuel and cognitive decline: Three nationwide cohort studies in middle-aged and older population.

BACKGROUND: Household solid-fuel burning contributes to indoor air pollution and is linked to poor cognitive function, but how solid cooking fuel use leads to cognitive decline over time is not well elaborated. OBJECTIVE: We examine the associations of solid cooking fuel with cognitive function among three nationally representative cohorts. METHODS: This study uses data from the 2010-2018 China Family Panel Studies (CFPS), the 2011-2018 China Health and Retirement Longitudinal Study (CHARLS) and the 2003-2015 Mexican Health and Aging Study (MHAS) in adults over the age of 50. Time varying Cox model was conducted to measure the association between cooking fuel types and cognitive decline. Mediation analysis was used to estimate the potential mediation effects on the associations of cooking fuel types with cognitive decline risk. RESULTS: Respondents in CFPS, CHARLS, and MHAS relied on solid cooking fuel at baseline approximately 56 %, 51 %, and 12 %, respectively. Using solid fuel was consistently associated with higher risk of cognitive decline in three cohorts (CFPS: HR = 1.300 [95 % CI: 1.201, 1.407], CHARLS: HR = 1.179 [95 % CI: 1.059, 1.312], MHAS: HR = 1.237 [95 % CI: 1.123, 1.362]). Compared to those with persistent solid fuel, persistent clean fuel and change from solid fuel to clean fuel were associated with a lower risk of cognitive decline. Hypertension, diabetes, physical activity, dyslipidemia and high-density lipoprotein cholesterol (HDL-C) may partially mediate the cognitive decline caused by solid fuel use. Of the cognitive decline burden, 18.23 % (95 % CI: 12.21 %, 24.73 %) in CFPS, 8.90 % (95 % CI: 2.93 %, 15.52 %) in CHARLS and 2.92 % (95 % CI: 1.52 %, 4.46 %) in MHAS of cognitive decline cases attributable to solid cooking fuel use. CONCLUSION: The use of solid cooking fuel is associated with a higher risk of cognitive decline. It is essential to promote the expanded use of clean fuel to protect cognitive health.