Mitophagy mediated by HIF-1α/FUNDC1 signaling in tubular cells protects against renal ischemia/reperfusion injury.

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.

Tailorable optical properties of polymer nanodots for triple-mode fluorescence detection of nucleic acids.

We present a triple-mode nanosensor platform for nucleic acid detection utilizing fluorescence anisotropy and Förster resonance energy transfer (FRET) strategies. The self-assembled nanoprobes serve as mass amplifiers, nanoquenchers, or nanodonors, exhibiting high FRET efficiencies (64.4-86.5%) and demonstrating excellent detection capabilities in DNA and microRNA analysis.

Design method for eliminating spectral line tilt in a multiple sub-pupil ultra-spectral imager (MSPUI).

A multiple sub-pupil ultra-spectral imaging system designed with a single spectrometer and detector can simultaneously detect multiple-channel spectra with ultra-high spectral resolution. However, due to using a prism in the system's front end, the nonlinear dispersion introduces spectral line tilt in the imaging spectra. This phenomenon can lead to bias in the final spectral data. To eliminate this issue, we propose a new design by introducing a second prism to correct this spectral tilt in the system. The angle of spectral line tilt generated by the nonlinear dispersion of the first prism is derived. It provides the theoretical basis for characterizing the second complementary prism. Finally, a UV multiple sub-pupil ultra-spectral imaging system is designed. The system employs two pupil separation prisms and one flat panel array to segment the pupil in three channels, each operating within spectral ranges of 180∼210 nm, 275∼305 nm, and 370∼400 nm, respectively. The spectral resolutions in all three channels are better than 0.1 nm. The corrected spectral line tilt is less than 1/3 of a pixel in the two channels with pupil separation prisms. At a Nyquist frequency of 30 lp/mm, the modulation transfer functions of all three channels are greater than 0.7, ensuring imaging quality. The design results indicate that the method proposed in this paper, utilizing complementary prisms, can effectively correct the spectral line tilt caused by the nonlinear dispersion of the pupil separation prisms. This design approach can be a reference for developing multiple sub-pupil ultra-spectral imaging systems.

Impact of a pandemic shock on unmet medical needs of middle-aged and older adults in 10 countries.

OBJECTIVE: The objective is to explore the impact of the pandemic shock on the unmet medical needs of middle-aged and older adults worldwide. METHODS: The COVID-19 pandemic starting in 2020 was used as a quasiexperiment. Exposure to the pandemic was defined based on an individual's context within the global pandemic. Data were obtained from the Integrated Values Surveys. A total of 11 932 middle-aged and older adults aged 45 years and above from 10 countries where the surveys conducted two times during 2011 and 2022 were analysed. We used logistic regression models with the difference-in-difference method to estimate the impact of pandemic exposure on unmet medical needs by comparing differences before and after the pandemic across areas with varying degrees of severity. RESULTS: Among the 11 932 middle-aged and older adults, 3647 reported unmet medical needs, with a pooled unmet rate of 30.56% (95% CI: 29.74% to 31.40%). The pandemic significantly increased the risk of unmet medical needs among middle-aged and older adults (OR: 2.33, 95% CI: 1.94 to 2.79). The deleterious effect of the pandemic on unmet medical needs was prevalent among middle-aged adults (2.53, 2.00 to 3.20) and older adults (2.00, 1.48 to 2.69), as well as among men (2.24, 1.74 to 2.90) and women (2.34, 1.82 to 3.03). The results remained robust in a series of sensitivity analyses. CONCLUSION: These findings suggest that efforts should be made by policymakers and healthcare professionals to balance healthcare resources to adequately address the comprehensive healthcare demands of individuals regarding multiple health issues, taking into account the challenges posed by pandemics.

[Sequential mediating role of digital participation and health lifestyle in the relationship between socioeconomic status and depression of older adults].

OBJECTIVE: To explore the potential mechanisms of the relationship between socioeconomic status (SES) and depression of Chinese older adults through the mediating role of digital participation and health lifestyle. METHODS: Using the nationally representative data from the China Family Panel Studies in 2020, 4 846 participants aged 60 years and older were analyzed in our study. We explored the potential mechanisms of the relationship between SES and depression of Chinese older adults in the digital era through a chain multiple mediating effects model. The KHB (The Karlson, Holm, and Breen) method was used to analyze the mediating role of digital participation and health lifestyle and the proportion of mediating effect between the two was also calculated. A series of robustness tests were further conducted and the fit of the model was checked by structural equation modeling. RESULTS: The mean age of the 4 846 older adults included in this study was (68.20±5.07) years, 48.06% of whom were female and 51.94% were male. The KHB results showed that both digital participation and health lifestyle could mediate the relationship between SES and depression of older adults (P < 0.000 1) and the mediating role of health lifestyle accounted for a greater proportion than digital participation. And our study mainly found three potential pathways of SES and depression of older adults, including: (1) SES → digital participation → health lifestyle → depression, (2) SES → health lifestyle → depression, and (3) SES → depression. Structural equation modeling tests proved the overall fit of the model in this study. CONCLUSION: Our findings showed that in the digital age, in addition to the direct relationship between SES and depression of older adults, and the health lifestyle as a mediator between the relationship, there is also a sequential mediating role of digital participation and health lifestyle to reduce the risk of depression. The findings suggest that we should pay more attention to the probability of the digital divide exacerbating health inequalities and socioeconomic inequalities accumulation in the digital age and promote the co-progress of digital literacy and health literacy among older adults.

Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

Effects of acute exposure to hypoxia on sleep structure in healthy adults: A systematic review.

The sleep quality of lowlanders in hypoxic environments has become increasingly important with an increase in highland and alpine activities. This study aimed to identify the effects of acute exposure to hypoxia on the sleep structure of lowlanders and to analyze the changes in sleep indicators at varying levels of hypoxia. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-three studies were screened and included in the quantitative analysis. The results showed that acute exposure to hypoxia reduced sleep quality in lowlanders. Post-sleep arousal events and the percentage of N1 were significantly increased, whereas total sleep time, sleep efficiency, and the percentage of N3 and rapid eye movement sleep were significantly decreased in hypoxic environments. Acute exposure to hypoxia had the greatest negative impact on wakefulness after sleep onset (WASO). In addition, a larger decrease in sleep efficiency and higher increase in the percentages of N1 and WASO were observed when lowlanders were exposed to higher levels of hypoxia. This study clarifies the quantitative effects of acute hypoxic exposure on sleep in lowlanders based on original studies and explains the sleep disorders faced by lowlanders in hypoxic environments.

Right ventricular scalloping index as CMR-derived marker for diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: The cardiac magnetic resonance (CMR) evaluation of right ventricular (RV) morphologic abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is subjective. Here we aimed to use a quantitative index, the right ventricular scalloping index (RVSI), to standardize the measurement of RV free wall scalloping and aid in the imaging diagnosis. METHODS: We retrospectively included 15 patients with definite ARVC and 45 age- and sex-matched patients with idiopathic right ventricular outflow tract ventricular arrhythmia (RVOT-VA) as controls. The RVSI was measured from cine images on four-chamber view to evaluate its ability to distinguish between ARVC and RVOT-VA patients. Other cardiac functional parameters including strain analysis were also performed. RESULTS: The RVSI was significantly higher in the ARVC than RVOT-VA group (1.56±0.23 vs. 1.30±0.08, p<0.001). The diagnostic performance of the RVSI was superior to the RV global longitudinal, circumferential, and radial strains, RV ejection fraction, and RV end-diastolic volume index. The RVSI demonstrated high intra- and interobserver reliability (intraclass correlation coefficient, 0.94 and 0.96, respectively). RVSI was a strong discriminator between ARVC and RVOT-VA patients (Area under curve [AUC], 0.91; 95% confidence interval [CI], 0.82-0.99). A cut-off value of RVSI ≥ 1.49 provided an accuracy of 90.0%, specificity of 97.8%, sensitivity of 66.7%, positive predictive value (PPV) of 90.9%, and a negative predictive value (NPV) of 89.8%. In a multivariable analysis, a family history of ARVC or sudden cardiac death (odds ratio, 38.71; 95% confidence interval, 1.48-1011.05; p=0.028) and an RVSI ≥ 1.49 (odds ratio, 64.72; 95% confidence interval, 4.58-914.63; p=0.002) remained predictive of definite ARVC. CONCLUSION: RVSI is a quantitative method with good performance for the diagnosis of definite ARVC.

Online biomedical named entities recognition by data and knowledge-driven model.

Named entity recognition (NER) is an important task for the natural language processing of biomedical text. Currently, most NER studies standardized biomedical text, but NER for unstandardized biomedical text draws less attention from researchers. Named entities in online biomedical text exist with errors and polymorphisms, which negatively impact NER models' performance and impede support from knowledge representation methods. In this paper, we propose a neural network method that can effectively recognize entities in unstandardized online medical/health text. We introduce a new pre-training scheme that uses large-scale online question-answering pairs to enhance transformers' model capacity on online biomedical text. Moreover, we supply models with knowledge representations from a knowledge base called multi-channel knowledge labels, and this method overcomes the restriction from languages, like Chinese, that require word segmentation tools to represent knowledge. Our model outperforms other baseline methods significantly in experiments on a dataset for Chinese online medical entity recognition and achieves state-of-the-art results.

Enhanced survival with lymphadenectomy in early-stage metachronous second primary lung cancer: A retrospective analysis.

INTRODUCTION: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer(MSPLC) remains poorly understood. This retrospective study aims to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. METHODS: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% among in the non-lymphadenectomy group (HR 0.76; 95% confidence interval 0.64-0.90; P=0.002). CONCLUSION: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggests the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

Implication of sleep apnea for cardiac remodeling in patients with hypertrophic cardiomyopathy.

OBJECTIVES: Cardiac remodeling is a life-long process in hypertrophic cardiomyopathy (HCM), and if uncontrolled, would cause substantial morbidity and mortality. Sleep apnea (SA) is a common comorbidity in HCM. This study aimed to investigate the relationship between SA and cardiac remodeling in a large series of patients with HCM. METHODS: A total of 606 patients with HCM who underwent sleep evaluations at Fuwai Hospital were included. Parameters of cardiac remodeling were evaluated by echocardiographic studies. RESULTS: SA was present in 363 (59.9%) patients. Left ventricular (LV) end-diastolic diameter (P < 0.001), left atrial (LA) diameter (P = 0.024), ascending aortic diameter (P < 0.001) all increased and maximal end-diastolic wall thickness (P < 0.001) decreased with the severity of SA. After adjustment for sex, age, body mass index, hypertension, hyperlipidemia, diabetes, coronary artery disease and cigarette use, log (apnea-hypopnea index+1) was independently correlated with increasing LV end-diastolic diameter (ß = 0.729, P = 0.003) and deceasing maximal end-diastolic wall thickness (ß = -0.503, P = 0.009). Log (percentage of total sleep time spent with oxygen saturation<90% + 1) was independently correlated with increasing LV end-diastolic diameter (ß = 0.609, P = 0.004) and LA diameter (ß = 0.695, P = 0.006). Severity of SA (severe SA with odds ratio, 2.38; 95% CI, 1.20-4.70; P = 0.013), log (apnea-hypopnea index+1) (OR, 1.28; 95% CI, 1.01-1.63; P = 0.045) and log (percentage of total sleep time spent with oxygen saturation<90% + 1) (OR, 1.31; 95% CI, 1.08-1.59; P = 0.006) were also independently associated with LV enlargement. CONCLUSIONS: Severity of SA is independently associated with cardiac remodeling indicating a trend toward enlarged chamber size and thinned wall. Clinical trials are required to determine whether treatment of SA improves cardiac remodeling and long-term outcomes in patients with HCM.

Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease.

Background: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear. Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained. Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated. Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated. Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

Comparison of the efficacy of neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal in treatment of hypertensive cerebral hemorrhage.

OBJECTIVE: To compare neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal for treatment of hypertensive cerebral hemorrhage. METHOD: Ninety-one patients with hypertensive cerebral hemorrhage admitted to our neurosurgery department from June 2022 to May 2023 were selected: 47 patients who underwent endoscopic hematoma removal with the aid of neuronavigation in observation Group A and 44 who underwent intracerebral hematoma puncture and drainage in control Group B. The duration of surgery, intraoperative bleeding, hematoma clearance rate, pre- and postoperative GCS score, National Institutes of Health Stroke Scale (NIHSS) score, mRS score and postoperative complications were compared between the two groups. RESULTS: The duration of surgery, intraoperative bleeding and hematoma clearance were significantly lower in Group B than in Group A (p < 0.05). Conversely, no significant differences in the preoperative, 7-day postoperative, 14-day postoperative or 1-month postoperative GCS or NIHSS scores or the posthealing mRS score were observed between Groups A and B. However, the incidence of postoperative complications was significantly greater in Group B than in Group A (p < 0.05), with the most significant difference in incidence of intracranial infection (p < 0.05). CONCLUSION: Both neuronavigation-assisted intracerebral hematoma puncture and drainage and neuroendoscopic hematoma removal are effective at improving the outcome of patients with hypertensive cerebral hemorrhage. The disadvantage of neuronavigation is that the incidence of complications is significantly greater than that of other methods; postoperative care and prevention of complications should be strengthened in clinical practice.

Preparation of Aminated Sodium Lignosulfonate and Efficient Adsorption of Methyl Blue Dye.

The aminated sodium lignosulfonate (AELS) was prepared through a Mannich reaction and characterized via FT-IR, TG, SEM and XPS in this study. Subsequently, the adsorption capacity of AELS for methyl blue (MB) was evaluated under various conditions such as pH, adsorbent dosage, contact time, initial concentration and temperature. The adsorption kinetics, isotherms and thermodynamics of AELS for methyl blue were investigated and analyzed. The results were found to closely adhere to the pseudo-second-order kinetic model and Langmuir isotherm model, suggesting a single-molecular-layer adsorption process. Notably, the maximum adsorption capacity of AELS for methyl blue (153.42 mg g-1) was achieved under the specified conditions (T = 298 K, MAELS = 0.01 g, pH = 6, VMB = 25 mL, C0 = 300 mg L-1). The adsorption process was determined to be spontaneous and endothermic. Following five adsorption cycles, the adsorption capacity exhibited a minimal reduction from 118.99 mg g-1 to 114.33 mg g-1, indicating good stability. This study contributes to the advancement of utilizing natural resources effectively and sustainably.

The early-stage impacts of shock events on adult sleep: Lessons from the COVID-19 pandemic.

The present study aims to estimate the early-stage association of the coronavirus disease 2019 (COVID-19) pandemic with sleep duration, 4 months after the initial outbreak, at a national level. Using the China Family Panel Studies in 2018 and its follow-up in 2020, 16,563 adult participants were analyzed in our study. The first wave transmissibility of the COVID-19 pandemic in mainland China was used as a quasi-natural experiment. The difference in difference method was employed to compare variations across participants interviewed before or after the pandemic and between groups from provinces with different COVID-19 severity. The study observed a decline in workday sleep duration among adults, regardless of their employment status. Specifically, working adults experienced a significant decrease in sleep duration on work days (-1.54, 95% confidence interval -2.16 to -0.92), alongside an increase on work-free days (2.41, 1.56-3.24), leading to a wider sleep discrepancy in sleep patterns (3.95, 3.31-4.59). Noteworthy, working-age adults (-2.00, -2.79 to -1.22) and males (-3.31, -4.31 to -2.30) exhibited greater sleep decreases on work days, whereas females exhibited a more pronounced disparity in sleep patterns (6.18, 4.73-7.63) between work and work-free days. The pandemic is significantly associated with prolonged changes in adults' sleep duration, including sleep decreases on work days and catch-up sleep on work-free days for working adults. To prepare for future global emergencies, the government may need to promote resilience to mitigate the pandemic's adverse impacts on the working population. Guaranteeing adequate sleep among working adults and reducing sleep debt should be prioritized in such efforts.

The effect of clean cooking on the social participation of middle-aged and older adults in China: A prospective cohort study.

BACKGROUND: Indoor air pollution stemming from the use of solid fuels, such as biomass and coal, is a significant public health concern, especially in developing countries. Understanding the connection between indoor air quality and social participation is essential for crafting effective interventions and enhancing the well-being of these populations. This study aims to investigate the influence of indoor air pollution on social participation among middle-aged and olderly individuals in China. METHODS: This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS), encompassing 17,711 samples, to investigate the link between cooking fuel type and social participation. Survival analysis Cox regression was used, complemented by logistic regression for supplementary analyses. FINDINGS: Upon accounting for confounding factors, the analysis revealed that individuals who consistently used clean fuels and those who switched to clean fuels exhibited a significantly higher likelihood of increased social participation compared to those using solid fuels. The hazard ratios were 1.31 (95 % CI: 1.19-1.44) and 1.39 (95 % CI: 1.28-1.51), respectively. These findings remained consistent across various regression models and showed no signs of population heterogeneity. Furthermore, this study found that in the investigation of mediating effects, chronic disease did not demonstrate any mediating effect on social participation. However, the mediating effects of depression level and IADL (Instrumental Activities of Daily Living) were significant, accounting for 1.82 % and 7.35 % of the impact of clean cooking on social participation, respectively. INTERPRETATION: This study provides compelling evidence that adopting clean cooking practices positively influences social participation among middle-aged and older individuals in China. We recommend that governments, communities, and individuals prioritize measures to enhance indoor air quality.

Potential effects of individual and combined exposure to tetraconazole and cadmium on zebrafish from the perspective of enantioselectivity and intestinal microbiota.

As the wide use of pesticides, they could form combined pollution with heavy metals, which would affect their environmental behaviors and toxic effects. Particularly, the effects would be more intricate for chiral pesticides. In this study, the accumulation and dissipation trends of tetraconazole enantiomers in zebrafish were investigated by individual and combined exposure of cadmium (Cd) and tetraconazole (including racemate and enantiomers) after confirming the absolute configuration of tetraconazole enantiomer. For the enantiomer treatments, Cd enhanced the accumulation of S-(+)-tetraconazole, but declined the concentrations of R-(-)-tetraconazole in zebrafish. The dissipation half-lives of tetraconazole enantiomers were extended by 1.65-1.44 times after the combined exposure of Cd and enantiomers. The community richness and diversity of intestinal microbiota were reduced in all treatments, and there were significant differences in R + Cd treatment. There was synergistic effect between Cd and S-(+)-tetraconazole for the effects on the relative abundances of Fusobacteria, Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. For R-(-)-tetraconazole, Cd mainly exhibited antagonistic effects. In the combined exposure of Cd and S-(+)-tetraconazole, the relative abundance changes of Cetobacterium (Fusobacteria, increase) and Edwardsiella (Proteobacteria, decrease) might affect the carbohydrate metabolism and energy metabolism, and led to the increase of S-(+)-tetraconazole bioaccumulation concentration. In the combined exposure of Cd and R-(-)-tetraconazole, Cd could increase the relative abundance of Edwardsiella (Proteobacteria), and affect the amino acid metabolism, which might reduce the bioaccumulation concentration of R-(-)-tetraconazole. This study reported for the first time that the abundance of intestinal microbiota in zebrafish might affect the bioaccumulation and dissipation of tetraconazole enantiomers, and would provide new insight for the study of combined pollutions.

Iron/ROS/Itga3 mediated accelerated depletion of hippocampal neural stem cell pool contributes to cognitive impairment after hemorrhagic stroke.

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.