Minocycline prevents photoreceptor degeneration in Retinitis pigmentosa through modulating mitochondrial homeostasis.

Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.

Exposure to PM2.5 and its constituents is associated with metabolic dysfunction-associated fatty liver disease: a cohort study in Northwest of China.

Accumulating animal studies have demonstrated associations between ambient air pollution (AP) and metabolic dysfunction-associated fatty liver disease (MAFLD), but relevant epidemiological evidence is limited. We evaluated the association of long-term exposure to AP with the risk of incident MAFLD in Northwest China. The average AP concentration between baseline and follow-up was used to assess individual exposure levels. Cox proportional hazard models and restricted cubic spline functions (RCS) were used to estimate the association of PM2.5 and its constituents with the risk of MAFLD and the dose-response relationship. Quantile g-computation was used to assess the joint effects of mixed exposure to air pollutants on MAFLD and the weights of the various pollutants. We observed 1516 cases of new-onset MAFLD, with an incidence of 10.89%. Increased exposure to pollutants was significantly associated with increased odds of MAFLD, with hazard ratios (HRs) of 2.93 (95% CI: 1.22, 7.00), 2.86 (1.44, 5.66), 7.55 (3.39, 16.84), 4.83 (1.89, 12.38), 3.35 (1.35, 8.34), 1.89 (1.02, 1.62) for each interquartile range increase in PM2.5, SO42-, NO3-, NH4+, OM, and BC, respectively. Stratified analyses suggested that females, frequent exercisers and never-drinkers were more susceptible to MAFLD associated with ambient PM2.5 and its constituents. Mixed exposure to SO42-, NO3-, NH4+, OM and BC was associated with an increased risk of MAFLD, and the weight of BC had the strongest effect on MAFLD. Exposure to ambient PM2.5 and its constituents increased the risk of MAFLD.

Predictive value of total cholesterol to high-density lipoprotein cholesterol ratio for chronic kidney disease among adult male and female in Northwest China.

Background: Studies have found that the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females. Methods: Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL-C, TC/HDL-C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve. Results: During a mean follow-up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL-C and TC/HDL-C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05-1.31), 0.84 (0.71-0.99), and 1.15 (1.06-1.25) for males, 0.94 (0.78-1.13), 0.58 (0.35-0.95), and 1.19 (1.01-1.40) for females, respectively. The results also showed that TC, HDL-C, and TC/HDL-C were associated with CKD in a linear dose-response relationship. The TC/HDL-C had the largest area under the curve (AUC) compared to TC and HDL-C, and the AUC among the females was larger than that among males. Conclusions: The TC/HDL-C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL-C, especially in females.

Association between urinary polycyclic aromatic hydrocarbons and risk of metabolic associated fatty liver disease.

OBJECTIVE: To investigate the effect of urinary PAHs on MAFLD. METHODS: The study included 3,136 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2016. Among them, 1,056 participants were diagnosed with MAFLD and were designated as the case group. The analysis of the relationship between monohydroxy metabolites of seven PAHs in urine and MAFLD was carried out using logistic regression and Bayesian kernel regression (BKMR) models. RESULTS: In single-pollutant models, the concentration of 2-hydroxynaphthalene (2-OHNAP) was positively correlated with MAFLD (OR = 1.47, 95% CI 1.18, 1.84), whereas 3-hydroxyfluorene (3-OHFLU) and 1-hydroxypyrene (1-OHPYR) demonstrated a negative correlation with MAFLD (OR = 0.59, 95% CI 0.48 0.73; OR = 0.70, 95% CI 0.55, 0.89). Conversely, in multi-pollutant models, 2-OHNAP, 2-hydroxyfluorene (2-OHFLU), 2-hydroxyphenanthrene, and 3-hydroxyphenanthrene (2&3-OHPHE) displayed positive correlations with MAFLD (OR = 6.17, 95% CI 3.15, 12.07; OR = 2.59, 95% CI 1.37, 4.89). However, 3-OHFLU and 1-OHPYR continued to exhibit negative correlations with MAFLD (OR = 0.09, 95% CI 0.05, 0.15; OR = 0.62, 95% CI 0.43, 0.88). Notably, the BKMR analysis mixtures approach did not indicate a significant joint effect of multiple PAHs on MAFLD, but identified interactions between 3-OHFLU and 2-OHFLU, 1-OHPYR and 2-OHFLU, and 1-OHPYR and 3-OHFLU. CONCLUSION: No significant association was found between mixed PAHs exposure and the risk of MAFLD. However, interactions were observed between 3-OHFLU and 2-OHFLU. Both 2-OHFLU and 2&3-OHPHE exposure are significant risk factors for MAFLD, whereas 3-OHFLU is a key protective factor for the disease.

Construction of yeast microbial consortia for petroleum hydrocarbons degradation.

Microbial degradation of petroleum hydrocarbons plays a vital role in mitigating petroleum contamination and heavy oil extraction. In this study, a Saccharomyces cerevisiae capable of degrading hexadecane has been successfully engineered, achieving a maximum degradation rate of up to 20.42%. However, the degradation ability of this strain decreased under various pressure conditions such as high temperature, high osmotic pressure, and acidity conditions. Therefore, a S. cerevisiae with high tolerance to these conditions has been constructed. And then, we constructed an "anti-stress hydrocarbon-degrading" consortium comprising engineered yeast strain SAH03, which degrades hexadecane, and glutathione synthetic yeast YGSH10, which provides stress resistance. This consortium was able to restore the degradation ability of SAH03 under various pressure conditions, particularly exhibiting a significant increase in degradation rate from 5.04% to 17.04% under high osmotic pressure. This study offers a novel approach for improving microbial degradation of petroleum hydrocarbons.

Exposure to PM2.5 and its five constituents is associated with the incidence of type 2 diabetes mellitus: a prospective cohort study in northwest China.

Studies have demonstrated that fine particulate matter (PM2.5) is an underlying risk factor for type 2 diabetes mellitus (T2DM), but evidence exploring the relationship between PM2.5 chemical components and T2DM was extremely limited, to investigate the effects of long-term exposure to PM2.5 and its five constituents (sulfate [SO42-], nitrate [NO3-], ammonium [NH4+]), organic matter [OM] and black carbon [BC]) on incidence of T2DM. Based on the "Jinchang Cohort" platform, a total of 19,884 participants were selected for analysis. Daily average concentrations of pollutants were gained from Tracking Air Pollution in China (TAP). Cox proportional hazards regression models were utilized to estimate the hazard ratios (HR) and 95% confidence interval (CI) in single-pollutant models, restricted cubic splines functions were used to examine the dose-response relationships, and quantile g-computation (QgC) was applied to evaluate the combined effect of PM2.5 compositions on T2DM. Stratification analysis was also considered. A total of 791 developed new cases of T2DM were observed during a follow-up period of 45254.16 person-years. The concentrations of PM2.5, NO3-, NH4+, OM and BC were significantly associated with incidence of T2DM (P-trend < 0.05), with the HRs in the highest quartiles of 2.16 (95% CI 1.79, 2.62), 1.43 (95% CI 1.16, 1.75), 1.75 (95% CI 1.45, 2.11), 1.31 (95% CI 1.08, 1.59) and 1.79 (95% CI 1.46, 2.21), respectively. Findings of QgC model showed a noticeably positive joint effect of one quartile increase in PM2.5 constituents on increased T2DM morbidity (HR 1.27, 95% CI 1.09, 1.49), and BC (32.7%) contributed the most to the overall effect. The drinkers, workers and subjects with hypertension, obesity, higher physical activity, and lower education and income were generally more susceptible to PM2.5 components hazards. Long-term exposure to PM2.5 and its components (i.e., NO3-, NH4+, OM, BC) was positively correlated with T2DM incidence. Moreover, BC may be the most responsible for the association between PM2.5 constituents and T2DM. In the future, more epidemiological and experimental studies are needed to identify the link and potential biological mechanisms.

Effect of CVAI on the incidence of MASLD compared to BMI in populations with different body types: A prospective cohort study in China.

BACKGROUND AND AIMS: To explore the relationship between body mass index (BMI), chinese visceral adiposity index (CVAI) and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in populations with different body types defined by BMI. METHODS AND RESULTS: 24 191 participants from the Jinchang cohort were involved in the prospective cohort study with a 2.3-year follow-up. Information from epidemiological investigations, comprehensive health examinations and biochemical examinations was collected. MASLD was assessed by abdominal ultrasonography. BMI and CVAI were calculated using recognized formulas. Cox regressions, Restricted cubic spline (RCS) and Receiver operating characteristic (ROC) analysis were performed. The risk of MASLD increased with the increase in BMI and CVAI (Ptrend <0.001), and there was a nonlinear dose-response relationship. In the total population, BMI and CVAI increased the risk of MASLD with adjusted HR (95%CI) of 1.097 (1.091-1.104) and 1.024 (1.023-1.026), respectively. The results were similar in the lean and overweight/obese groups. There was also a nonlinear relationship between CVAI and MASLD (Pnon-linearity<0.001), no matter in which group. The area under the curve of CVAI was significantly higher than that of BMI in females with different body types, and the areas in the whole females were 0.802 (95%CI: 0.787-0.818) and 0.764 (95%CI: 0.747-0.780), respectively. There was no significant difference in the ability of BMI and CVAI to predict MASLD in all-sex and males, either in lean or overweight/obese groups. CONCLUSIONS: CVAI and BMI were independently associated with the risk of MASLD regardless of body types defined by BMI, and CVAI showed better diagnostic ability for MASLD in females.

A study of temperature variability on admissions and deaths for cardiovascular diseases in Northwestern China.

OBJECTIVE: To explore the effect of temperature variability (TV) on admissions and deaths for cardiovascular diseases (CVDs). METHOD: The admissions data of CVDs were collected in 4 general hospitals in Jinchang City, Gansu Province from 2013 to 2016. The monitoring data of death for CVDs from 2013 to 2017 were collected through the Jinchang City Center for Disease Control and Prevention. Distributed lag nonlinear model (DLNM) was combined to analyze the effects of TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) on the admissions and deaths for CVDs after adjusting confounding effects. Stratified analysis was conducted by age and gender. Then the attribution risk of TV was evaluated. RESULTS: There was a broadly linear correlation between TV and the admissions and deaths for CVDs, but only the association between TV and outpatient and emergency room (O&ER) visits for CVDs have statistically significant. DTV and HTV have similar lag effect. Every 1 ℃ increase in DTV and HTV was associated with a 3.61% (95% CI: 1.19% ~ 6.08%), 3.03% (95% CI: 0.27% ~ 5.86%) increase in O&ER visits for CVDs, respectively. There were 22.75% and 14.15% O&ER visits for CVDs can attribute to DTV and HTV exposure during 2013-2016. Males and the elderly may be more sensitive to the changes of TV. Greater effect of TV was observed in non-heating season than in heating season. CONCLUSION: TV was an independent risk factor for the increase of O&ER visits for CVDs, suggesting effective guidance such as strengthening the timely prevention for vulnerable groups before or after exposure, which has important implications for risk management of CVDs.

The bidirectional relationship between NAFLD and type 2 diabetes: A prospective population-based cohort study.

BACKGROUND AND AIMS: To explore the bidirectional relationship between NAFLD and type 2 diabetes and the possible directions of the main effect. METHODS AND RESULTS: 30 633 participants from the Jinchang cohort were enrolled. Firstly, cox proportional hazards regression model was used to assess the unidirectional causality between NAFLD and prediabetes and type 2 diabetes. Secondly, cross-lag path analysis model was conducted to estimate the bidirectional relationship between NAFLD and prediabetes and type 2 diabetes, and to determine the direction of the main effects. Finally, potential effect modifications were also considered by age, sex, hyperlipidemia, and overweight/obesity. We found that NAFLD increased the risk of prediabetes and type 2 diabetes with adjusted HR (95%CI) of 1.355(95%CI: 1.255-1.462) and 1.898(95%CI: 1.415-2.545), respectively. Prediabetes and type 2 diabetes also increased the risk of NAFLD, with adjusted HR (95%CI) of 1.245(95%CI: 1.115-1.392) and 1.592(95%CI: 1.373-1.846), respectively. Cross-lag path analysis showed that NAFLD significantly affected the incidence of prediabetes (ß = 0.285, P < 0.001), while the effect on type 2 diabetes was not statistically significant. The effect of prediabetes and type 2 diabetes on the risk of NAFLD was weak, and the path coefficients were 0.076 and 0.037, respectively. Stratified analyses showed similar results. CONCLUSION: This study provides evidence that there was a bidirectional causal association between NAFLD and type 2 diabetes, and the progression from NAFLD through prediabetes to type 2 diabetes may be the main pathway.

Bioengineering for the Microbial Degradation of Petroleum Hydrocarbon Contaminants.

Petroleum hydrocarbons are relatively recalcitrant compounds, and as contaminants, they are one of the most serious environmental problems. n-Alkanes are important constituents of petroleum hydrocarbons. Advances in synthetic biology and metabolic engineering strategies have made n-alkane biodegradation more designable and maneuverable for solving environmental pollution problems. In the microbial degradation of n-alkanes, more and more degradation pathways, related genes, microbes, and alkane hydroxylases have been discovered, which provide a theoretical basis for the further construction of degrading strains and microbial communities. In this review, the current advances in the microbial degradation of n-alkanes under aerobic condition are summarized in four aspects, including the biodegradation pathways and related genes, alkane hydroxylases, engineered microbial chassis, and microbial community. Especially, the microbial communities of "Alkane-degrader and Alkane-degrader" and "Alkane-degrader and Helper" provide new ideas for the degradation of petroleum hydrocarbons. Surfactant producers and nitrogen providers as a "Helper" are discussed in depth. This review will be helpful to further achieve bioremediation of oil-polluted environments rapidly.

Research on Comprehensive Evaluation and Early Warning of Transmission Lines' Operation Status Based on Dynamic Cloud Computing.

The current methods for evaluating the operating condition of electricity transmission lines (ETLs) and providing early warning have several problems, such as the low correlation of data, ignoring the influence of seasonal factors, and strong subjectivity. This paper analyses the sensitive factors that influence dynamic key evaluation indices such as grounding resistance, sag, and wire corrosion, establishes the evaluation criteria of the ETL operation state, and proposes five ETL status levels and seven principles for selecting evaluation indices. Nine grade I evaluation indices and twenty-nine grade II evaluation indices, including passageway and meteorological environments, are determined. The cloud model theory is embedded and used to propose a warning technology for the operation state of ETLs based on inspection defect parameters and the cloud model. Combined with the inspection defect parameters of a line in the Baicheng district of Jilin Province and the critical evaluation index data such as grounding resistance, sag, and wire corrosion, which are used to calculate the timeliness of the data, the solid line is evaluated. The research shows that the dynamic evaluation model is correct and that the ETL status evaluation and early warning method have reasonable practicability.

Prevalence of chronic kidney disease in a city of Northwestern China: a cross-sectional study.

AIM: Chronic kidney disease (CKD) is increasingly recognized as a global health issue. There is a paucity of published data on the prevalence and risk factors of CKD in less-developed regions. This study aims to evaluate and update the prevalence and risk factors of CKD in a city of Northwestern China. METHODS: Based on a prospective cohort study, a cross-sectional baseline survey was conducted between 2011 and 2013. The data on the epidemiology interview, physical examination, and clinical laboratory test were all collected. In this study, 41,222 participants were selected from 48,001 workers in the baseline after excluding objects with incomplete information. The crude and standardized prevalence of CKD were calculated. An unconditional logistic regression model was used to analyze the risk factors associated with CKD among male and female. RESULTS: One thousand seven hundred eighty-eight people were diagnosed with CKD, including 1180 males and 608 females. The crude prevalence of CKD was 4.34% (4.78% males and 3.68% females). The standardized prevalence was 4.06% (4.51% males and 3.60% females). The prevalence of CKD increased with age and was higher in males than in females. In multivariable logistic regression, CKD was significantly associated with the increasing age, drinking, never or occasionally exercise, overweight or obesity, being unmarried, diabetes, hyperuricemia, dyslipidemia and hypertension. CONCLUSION: In this study, the prevalence of CKD was lower than that of the national cross-sectional study. Lifestyle, hypertension, diabetes, hyperuricemia and dyslipidemia were the main risk factors of CKD. The prevalence and risk factors differ between male and female.

Ambient temperature variability and blood pressure in a prospective cohort of 50,000 Chinese adults.

Blood pressure has been shown to change by outdoor temperature, but whether intra- and inter-day temperature variability (TV) will bring higher effect on BP is not clear. Based on a prospective cohort study, the mixed effect model was selected to estimate the relationship between TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) and BP (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP)) after adjusting for confounding variables. We found that there was a positive linear correlation between TV and BP. The results of DTV and HTV were basically consistent, but the effect estimates of HTV seemed to be larger. Gender, age, BMI, education level and BP status may modify the relationship between TV and BP. The effect of TV on BP was greater in non-heating season than in heating season. Our work contributes to a further macro mechanism evidence for the TV-CVDs association.

Effects of short-term exposure to gaseous pollutants on metabolic health indicators of patients with metabolic syndrome in Northwest China.

Currently few studies have explored the relationship between exposure to gaseous pollutants and metabolic health indicators in patients, especially in patients with metabolic syndrome (Mets). This study collected 15,520 patients with Mets in a prospective cohort of nearly 50,000 people with 7 years of follow-up from 2011 to 2017, and matched air pollutants and meteorological data during the same period. The mixed effects model was used to analyze the relationship between different short exposure windows (1-week, 1-month, 2-month, and 3-month) of gaseous pollutants (SO2, NO2, and O3) and the metabolic health indicators of patients after controlled the confounding factors. Stratified analysis was performed by demographic characteristics and behavioral factors. The effects of gaseous pollutants on patients with different Met components were also analyzed. The results showed that the short-term exposure to SO2, NO2, and O3 had a certain effect on the metabolic health indicators of patients with Mets in different exposure windows, and with the extension of the exposure window period, the effects increased. The stratified analysis showed that gender, age, and life behaviors might modify these detrimental effects. In addition, the effects of gaseous pollutants on metabolic health indicators in G4 and G7 were more obvious than other Met components, and the effects of gaseous pollutants on the level of LDL-C were found to be statistically significant in most components. Therefore, patients with Mets should pay more attention to the influence of gaseous pollutants to take appropriate protection to reduce potential health risk.

Nomogram for prediction of diabetic retinopathy in patients with type 2 diabetes mellitus: A retrospective study.

OBJECTIVE: To develop a nomogram for the risk of diabetic retinopathy (DR) among type 2 diabetes mellitus (T2DM). METHODS: Questionnaires, physical examinations and biochemical tests were performed on 5900 T2DM patients in the Second Hospital of Shijiazhuang. The least absolute shrinkage and selection operator regression was used to optimize feature selection, and the importance of selected features was analyzed by random forest. Logistic regression was performed with selected features, and the nomogram was established based on the results. The Harrell's C-statistic, bootstrap-corrected C-statistic, area under curve (AUC), calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to validate the discrimination, calibration and clinical usefulness of the nomogram, and further assessment was running by external validation. RESULTS: Predictors included duration of diabetes, diabetic neuropathy, diabetic kidney disease, diabetic foot, hyperlipidemia, hypoglycemic drugs, glycated albumin, Lactate dehydrogenase. The model displayed medium predictive power with a Harrell's C-statistic of 0.820, bootstrap-corrected C-statistic of 0.813 and AUC of 0.820 in the training set, and which was respectively 0.842, 0.835 and 0.842 in the validation set. The calibration curve displayed good agreement (P > 0.05). The DCA and CIC showed that the nomogram could be applied clinically if the risk threshold is between 2 % and 75 % and 2 %-88 % in validation set. CONCLUSIONS: This nomogram incorporating 8 features is useful to predict the risk of DR in T2DM patients.

Interaction effect of blood glucose and pressure on the risk of chronic kidney disease: a population-based prospective cohort study.

OBJECTIVE: To evaluate the interaction effect of blood glucose and blood pressure on the risk of chronic kidney disease (CKD). METHODS: 31,165 subjects were selected without CKD at baseline and had completed the first follow-up from "Jinchang cohort". Cox regression model and restricted cubic splines functions were used to evaluate the effects of blood glucose or pressure on the incidence of CKD and dose-response relationship after adjusting for confounding covariates. Synergic effect was assessed by the multiplicative or additive interaction scale. RESULTS: Among 31,165 subjects, 1307 new-onset CKD were observed during 68905.78 person-years follow-up, and the incidence density was 18.97 per 1000 person-years. The risk of CKD gradually increased with the increase of blood pressure in diabetes, pre-diabetes and normal groups (Ptrend < 0.05). And, the risk was greatest when SBP/DBP reached ≥150/≥110 mmHg in three groups, and HRs (95% CI) were 1.610 (1.070-2.422), 2.142 (1.396-3.288) and 2.455 (1.941-3.106), respectively. Additionally, among hypertension, pre-hypertension and normal groups, the risk of CKD increased by 16.0%, 14.3% and 25.2% for each 1 mmol/L of FPG. When FPG level was more than 9.0 mmol/L, the risk was greatest and adjusted HRs (95% CI) were 2.856 (2.176-3.748), 2.979 (1.828-4.854) and 7.520 (4.517-12.519). Furthermore, the risk was highest when hypertension was accompanied by diabetes (HR = 4.915, 95% CI: 3.923-6.157). This analysis supported a less than multiplicative effect (HR = 0.634, 95% CI: 0.417-0.964) for the interaction term of diabetes and hypertension, while there was no additive interaction towards CKD in all interaction term. CONCLUSIONS: Blood glucose and pressure were independent risk factors in incidence of CKD, but there was only a negative multiplicative interaction between hypertension and diabetes, but no additive interaction effect between them.

Apolipoprotein A1 Modulates Teff/Treg Balance Through Scavenger Receptor Class B Type I-Dependent Mechanisms in Experimental Autoimmune Uveitis.

Purpose: Experimental autoimmune uveitis (EAU) is a representative animal model of human uveitis. In this study, we investigated whether apolipoprotein A1 (APOA1) can alleviate EAU and explored its underlying mechanism. Methods: Mice were immunized with interphotoreceptor retinoid-binding protein 1-20 and treated with APOA1 or vehicle. The retinas, draining lymph nodes (DLNs), and spleens were analyzed. Isolated T cells were used for proliferation, differentiation, and function assays in vitro. Selective inhibitors and pathway agonists were used to study signaling pathways. The effect of APOA1 on peripheral blood mononuclear cells (PBMCs) from uveitis patients was also examined. Results: Administration of APOA1 ameliorated EAU. APOA1 suppressed pathogenic CD4+ T cell expansion in DLNs and spleen, and decreased the infiltration of effector T (Teff) cells into retina. APOA1 also inhibited T cell proliferation and T helper 1 cell differentiation in vitro and promoted regulatory T (Treg) cell differentiation. APOA1 restricted inflammatory cytokine production from lipopolysaccharide-stimulated PBMCs. Mechanistic studies revealed that the effect of APOA1 was mediated by scavenger receptor class B type I (SR-BI) and downstream signals including phosphatidylinositol 3-kinase/Protein kinase B (PKB, or Akt), p38 mitogen-activated protein kinase, and nuclear factor-κB. Conclusions: APOA1 ameliorates EAU by regulating the Teff/Treg partially through SR-BI. Our results suggest that APOA1 can be a therapeutic alternative for autoimmune uveitis.

Cohort Profile Update: the China Metal-Exposed workers Cohort Study (Jinchang Cohort).

The Jinchang Cohort was an ongoing 20-year ambispective cohort with unique metal exposures to an occupational population. From January 2014 to December 2019, the Jinchang Cohort has completed three phases of follow-up. The baseline cohort was completed from June 2011 to December 2013, and a total of 48 001 people were included. Three phases of follow-ups included 46 713, 41 888, and 40 530 participants, respectively. The death data were collected from 2001 to 2020. The epidemiological, physical examination, physiological, and biochemical data of the cohort were collected at baseline and during follow-up. Biological specimens were collected on the baseline to establish a biological specimen bank. The concentrations of metals in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The new areas of research aim to study the all-cases mortality, the burden of diseases, heavy metals and diseases, and the course of the chain from disease to high-risk outcomes using a combination of macro and micro means, which provided a scientific basis to explore the pathogenesis of multi-etiology and multi-disease and to evaluate the effects of the intervention measures in the population.

Hydroxychloroquine Alleviates EAU by Inhibiting Uveitogenic T Cells and Ameliorating Retinal Vascular Endothelial Cells Dysfunction.

Purpose: Inflammation triggers the activation of CD4+T cells and the breakdown of blood-retinal barrier, thus contributing to the pathology of experimental autoimmune uveitis (EAU). We explored the anti-inflammatory effect of hydroxychloroquine (HCQ) on EAU and the potential mechanisms active in T cells and retinal vascular endothelial cells (RVECs). Methods: C57BL/6J mice were immunized with interphotoreceptor retinoid binding protein 1-20 (IRBP1-20) to induce EAU and then treated with the vehicle or HCQ (100 mg/kg/day). On day 7, 14, 21, 30 and 60 after immunization, clinical scores were evaluated. On day 14, histopathological scores were assessed, and retinas, spleens, and lymph nodes were collected for quantitative polymerase chain reaction or flow cytometry analysis. RVEC dysfunction was induced by tumor necrosis factor α (TNF-α) stimulation. The expression of cytokines, chemokines, adhesion molecules, and lectin-like oxidized LDL receptor-1 (LOX-1)/nuclear factor κB (NF-κB) was measured in RVECs with or without HCQ. Results: HCQ treatment protected mice from uveitis, evidenced by reduced expression of inflammatory factors, chemokines, and adhesion molecules in the retina. In systemic immune response, HCQ inhibited the activation of naïve CD4+T cells and frequencies of T effector cells, and promoted T regulatory cells. HCQ decreased IRBP1-20-specific T cell responses and proliferation of CD4+T cells in vitro. Further studies established that TNF-α induced RVECs to express inflammatory cytokines, chemokines, and adhesion molecules, whereas HCQ alleviated the alterations via the LOX-1/NF-κB pathways. Conclusions: HCQ alleviates EAU by regulating the Teff/Treg balance and ameliorating RVECs dysfunction via the LOX-1/NF-κB axis. HCQ may be a promising therapeutic candidate for uveitis.

Comparing the Diagnostic Criteria of MAFLD and NAFLD in the Chinese Population: A Population-based Prospective Cohort Study.

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new concept, proposed in 2020; however, its applicability in Asia populations has yet to be evaluated. Therefore, we aimed to compare the difference in epidemiological and clinical characteristics between MAFLD and non-alcoholic fatty liver disease (NAFLD) among Asian populations. METHODS: Based on the Jinchang cohort, 30,633 participants were collected. The prevalence and incidence of MAFLD and NAFLD were used to analyze the epidemic characteristics and its overlapping effects. In addition, the corresponding clinical characteristics of the two diagnostic criteria populations were compared. RESULTS: The prevalence rates of MAFLD and NAFLD were 21.03% and 18.83%, respectively. After an average 2.28-year follow-up, the incidence densities of MAFLD and NAFLD were 41.58 per 1,000 person-years and 37.69 per 1,000 person-years, respectively. With the increase of baseline age, body mass index (BMI), and waist circumference (WC) levels, the prevalence and incidence of MAFLD and NAFLD were on the rise (all p trend<0.05). Among the total patients diagnosed at baseline or follow-up, most patients had both MAFLD and NAFLD, accounting for 78.84% and 82.88%, respectively. Compared with NAFLD, MAFLD patients had greater proportions of males and metabolic diseases (diabetes, dyslipidemia), and had higher BMI, WC, liver enzymes, blood glucose, and lipid levels in the baseline diagnosis patients (p<0.05). Additionally, lean MAFLD patients had higher metabolic disorders than lean NAFLD patients (p<0.05). CONCLUSIONS: Compared with NAFLD, the newly proposed definition of MAFLD is more practical and accurate, and it can help identify more fatty liver patients with high-risk diseases.