Gut microbial metabolism is linked to variations in circulating non-high density lipoprotein cholesterol.

BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-c) was a strong risk factor for incident cardiovascular diseases and proved to be a better target of lipid-lowering therapies. Recently, gut microbiota has been implicated in the regulation of host metabolism. However, its causal role in the variation of non-HDL-c remains unclear. METHODS: Microbial species and metabolic capacities were assessed with fecal metagenomics, and their associations with non-HDL-c were evaluated by Spearman correlation, followed by LASSO and linear regression adjusted for established cardiovascular risk factors. Moreover, integrative analysis with plasma metabolomics were performed to determine the key molecules linking microbial metabolism and variation of non-HDL-c. Furthermore, bi-directional mendelian randomization analysis was performed to determine the potential causal associations of selected species and metabolites with non-HDL-c. FINDINGS: Decreased Eubacterium rectale but increased Clostridium sp CAG_299 were causally linked to a higher level of non-HDL-c. A total of 16 microbial capacities were found to be independently associated with non-HDL-c after correcting for age, sex, demographics, lifestyles and comorbidities, with the strongest association observed for tricarboxylic acid (TCA) cycle. Furthermore, decreased 3-indolepropionic acid and N-methyltryptamine, resulting from suppressed capacities for microbial reductive TCA cycle, functioned as major microbial effectors to the elevation of circulating non-HDL-c. INTERPRETATION: Overall, our findings provided insight into the causal effects of gut microbes on non-HDL-c and uncovered a novel link between non-HDL-c and microbial metabolism, highlighting the possibility of regulating non-HDL-c by microbiota-modifying interventions. FUNDING: A full list of funding bodies can be found in the Sources of funding section.

Enhanced interactions among gut mycobiomes with the deterioration of glycemic control.

BACKGROUND: The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control. METHODS: 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their status of glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargeted liquid chromatography mass spectrometry. FINDINGS: The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic ß-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed that increased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity. CONCLUSIONS: Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM. FUNDINGS: This study was supported by MOST and NSFC of China.

Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia.

Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.

Bufotalin-loaded biomimetic Prussian blue nanoparticles for colorectal cancer chemo-photothermal ferroptosis therapy.

Purpose: We constructed biomimetic nanoparticles with biocompatible, tumor-targeting, laser-responsive properties for ferroptosis-induced colorectal cancer chemo-photothermal therapy, with the aim to realize double-hit ferroptosis treatment for colorectal cancer. Methods: The nanoparticles were prepared by first loading the chemotherapy drug bufotalin (CS-5) with Prussian blue (PB), then combining a hybridized erythrocyte-tumor membrane (M) with PB@CS-5 to produce PB@CS-5@M. The chemo-photothermal therapy efficiency of PB@CS-5@M was tested by in vitro and in vivo experiments. Results and conclusion: The combined PB and CS-5 act as promising ferroptosis inducers to enhance ferroptosis efficacy. The hyperthermia induced by laser stimulation can trigger PB to release CS-5 and iron and ferrous ions, which further promotes ferroptosis.

Ethical leadership and TMT decision-making of corporate social responsibility - a perspective of self-determination theory.

This study examines the impact of ethical leadership on top management team (TMT) decision-making regarding corporate social responsibility (CSR), considering the mediating role of TMT passion and the moderating role of performance stress. The study distinguishes between TMT harmonious and obsessive work passion and categorizes CSR as proactive and reactive. The findings reveal the following: (1) Ethical leadership positively influences proactive CSR, with TMT harmonious work passion acting as a positive mediator and TMT obsessive work passion playing a negative mediating role; (2) ethical leadership positively affects reactive CSR, with both TMT harmonious and obsessive work passion serving as positive mediators; (3) performance stress diminishes the impact of ethical leadership on TMT harmonious work passion; however, it amplifies the effect on TMT obsessive work passion. Consequently, the mediating effect of TMT harmonious work passion weakens, while the mediating effect of TMT obsessive work passion strengthens. This study emphasizes the significant role of TMT in CSR strategic decision-making and proposes a novel mediating mechanism through which ethical leadership drives CSR decision-making by considering TMT work passion. These findings reconcile the theoretical-practical conflict and have important theoretical and practical implications for enterprises in fulfilling their social responsibility.

The mediating effect of personality on mental workload and perceived professional benefits of nurses in East China.

BACKGROUND: Nursing work is a work with high-stress load, and nurses with different personality may have different subjective feelings about their workload. Therefore, it is particularly necessary to comprehend the perceived professional benefits of nurses engaged in nursing work under high-pressure background, especially during the epidemic period. This study explored the relationship between mental workload, personality, and perceived professional benefits of nurses, and offer advices for the intervention of nurses with different personality to improve their perceived professional benefits. MATERIALS AND METHODS: In this study, we used a cross-sectional study with a convenient sampling. 473 in-service nurses in Class A tertiary hospitals of Zhejiang Province were recruited by using the NASA Mission Load Index scale of nurses, the brief version of China's Big Five Personality Questionnaire, and the Nurses' perceived professional benefits questionnaire from July 2020 to March 2021. Sample size is 54.91%, and the response rate is 100%. Cronbach's alpha method was used to evaluate the reliability of the instruments. Descriptive statistical analysis was used to describe the socio-demographic data of the subject, and scores for research variables. The Mann-Whitney U-test, and Kruskal-Wallis H rank-sum test were used to compare the scores of perceived professional benefits with different demographic characteristics. Correlation analysis results were presented as the Spearman correlation coefficient. The plug-in v2.16.3 provided by SPSS software was used for linear regression analysis, and the deviation-corrected percentile Bootstrap method was used to examine the mediating role of personality (neuroticism, conscientiousness, agreeableness, openness and extroversion). RESULTS: Age, length of service in nursing, and record of formal schooling can affect nurses' perceived professional benefits. Mental workload, and perceived professional benefits were all above the median value. The mental workload was negatively correlated with perceived professional benefits (r= -0.129, P < 0.01), positively correlated with neuroticism (r = 0.242, P < 0.01), negatively correlated with agreeableness, openness, extroversion (r=-0.229~-0.221, P < 0.01), and negatively correlated with conscientiousness, but the differences were not significant. Nurses' perceived professional benefits were negatively correlated neuroticism (r=-0.109, P < 0.05), but positively associated with conscientiousness, agreeableness, openness, and extroversion (r = 0.098 ~ 0.326, P < 0.05). The mental workload can directly affect the perceived professional benefits in the direct effects, and can also affect the it through the mediating effect of agreeableness, extroversion, neuroticism, and openness. CONCLUSIONS: Age, length of service in nursing, and record of formal schooling could affect nurses' perceived professional benefits, and personality played a partial mediating role in the influence of mental workload on the perceived professional benefits. The results of this study can provide strategies for nurses' human resource management. According to different demographic factors, and personality, various measures should be taken to guide nurses to evaluate the mental workload correctly, reduce their emotional pressure, increase job resources, and improve their perceived professional benefits.

Daily stress, and mental health of professional degree graduate students in Chinese traditional medicine universities: the mediating role of learning career adaptation.

BACKGROUND: With the expansion of professional degree graduate students' enrollment in China education, the mental health of these professional degree graduate students in medical-related majors who are under pressure of study, scientific research, clinical practice, and employment should not be ignored. What is the mental health level of these graduate students under the effect of learning career adaptation (internal resources) in the face of daily stress (external factors)? The purpose of this study is to discuss the relationship between these variables, and the mediating role of learning career adaptation of professional degree graduate students in traditional Chinese medicine colleges, and universities, to provide a theoretical basis for improving the learning career adaptation of students, and improving the level of mental health. METHODS: A cross-sectional survey was conducted among 1593 professional degree graduate students majoring in clinical medicine, traditional Chinese medicine, and nursing in five traditional Chinese medicine universities. Finally, 660 questionnaires were returned, with a recovery rate of 41.43%. The scores of daily stress, learning career adaptation, and mental health were measured by Daily Stressors Scale for graduate students, graduate-students learning career adaptation scale, and General Mental Health Questionnaire (GHQ-20). Descriptive statistics were used to analyze the status quo of daily stress, learning career adaptation, and mental health. Pearson correlation analysis were used to analyze the relationship between them. we undertake analyses using structural equation modeling to construct the latent variable path model of daily stress, learning career adaptation on mental health. The significance level of the mediating effect was tested by the non-parametric percentile bootstrap method. RESULTS: The scores of mental health, daily stress, and learning career adaptation were 50.56 ± 10.80, 35.12 ± 19.55, and 67.13 ± 7.48 respectively. Daily stress was negatively correlated with the three dimensions of learning career adaptation: career confidence, focus on his career, and career control (P < 0.01). Daily stress was positively correlated with depression and anxiety (P < 0.01). Self-affirmation, depression, and anxiety were negatively correlated with career confidence, focus on his career, and career control (P < 0.05). Learning career adaptation plays a partial mediating role between daily stress, and mental health (p < 0.001), with an intermediate effect value of 0.127, representing 28.54% of the total effect. CONCLUSIONS: Mental health, learning career adaption of medical-related professional degree graduate students in traditional Chinese medical universities were at a moderate degree, and an upper-middle level respectively, while daily stress is to a lesser extent. Learning career adaptation mediates the relationship between daily stress, and mental health partially. To some extent, it can buffer the impact of daily stress on mental health, especially anxiety. The educational administrator could take various measures to improve the mental health of professional degree graduate students. It can also enhance their learning career adaptation from the perspective of individuals, and organizations to improve their mental health.

Cardiometabolic benefits of Lacticaseibacillus paracasei 8700:2: A randomized double-blind placebo-controlled trial.

BACKGROUND & AIMS: Modulating microbial metabolism via probiotic supplementation has been proposed as an attractive strategy for the prevention of cardiometabolic diseases. Recently, Lacticaseibacillus paracasei (L. paracasei) was reported to alleviate metabolic disorders in murine models, however, its beneficial effects in humans remain to be determined. This study evaluated whether L. paracasei supplementation could improve endothelial function and cardiometabolic health in subjects with metabolic syndrome (MetS). METHODS: In this randomized, double-blind and placebo-controlled trial among 130 participants with MetS, subjects were randomly assigned to placebo or L. paracasei 8700: 2 (10 billion CFU) daily for 12 weeks. Endothelial function was measured by flow-mediated slowing, and cardiometabolic health was determined by both components and severity of MetS. Ideal compliance was defined as consumption no less than 70% of the capsules. RESULTS: 130 individuals (mean [SD] age, 45.97 [7.11] years; 95 men [73.1%]) were enrolled and randomized to L. paracasei (n = 66) or placebo control (n = 64). Compared to placebo, L. paracasei supplementation led to a greater reduction in remnant cholesterol (-0.16 mmol/L, 95%CI: -0.29 mmol/L to -0.02 mmol/L; P = 0.024). Such a reduction in remnant cholesterol was significantly associated with improvement in endothelial function (r = -0.23, P = 0.027). In subjects with an ideal compliance with trial protocol, L. paracasei treatment additionally lowered triglycerides, alleviated MetS severity and delayed weight gain. On the contrary, no obvious effect on insulin sensitivity or pancreatic beta-cell function was observed after L. paracasei intervention. Moreover, regarding safety and tolerability, no significant between-group difference in protocol-specified adverse events of interest was observed. CONCLUSIONS: L. paracasei supplementation enhanced endothelial function potentially through downregulating remnant cholesterol levels. Our study provides a feasible and safe strategy for the prevention of cardiometabolic diseases in subjects with severe dyslipidemia and endothelial dysfunction. REGISTERED: Under ClinicalTrails.gov identifier NCT05005754.

Instrumental activities of daily living trajectories and risk of mild cognitive impairment among Chinese older adults: results of the Chinese longitudinal healthy longevity survey, 2002-2018.

Background: The association between the instrumental activities of daily living (IADL) score and the risk of initial cognitive function impairment is inconclusive. We aimed to identify distinctive IADL trajectories and examine their relationship with the onset of mild cognitive impairment (MCI) among Chinese older people. Methods: The study used six-wave longitudinal data from the Chinese Longitudinal Healthy Longevity Survey conducted between 2002 and 2018. It included a total of 11,044 Chinese people aged 65 years or older. A group-based trajectory model was used to identify distinctive trajectories of the IADL score, and the Cox proportional hazards model was used to explore the hazard ratio of various trajectories at the onset of MCI. Interaction analysis was used to analyze individual modification between the IADL trajectories and the onset of MCI. Finally, we adopted four types of sensitivity analysis to verify the robustness of the results. Results: During a median follow-up of 16 years, the incidence of MCI was 6.29 cases per 1,000 person-years (95% confidence interval [CI] 5.92-6.68). Three distinct IADL trajectory groups were identified: a low-risk IADL group (41.4%), an IADL group with increasing risk (28.5%), and a high-risk IADL group (30.4%). Using the Cox proportional hazards model after adjusting for covariates, we found that compared with the low risk IADL group, the hazard ratio of the IADL group with increasing risk was 4.49 (95% CI = 3.82-5.28), whereas that of the high-risk IADL group was 2.52 (95% CI 2.08-3.05). Treating the IADL group with increasing risk as the reference, the hazard ratio for the high-risk IADL group was 0.56 (95% CI 0.48-0.66). Interaction analyses showed that age and residence were significant moderators (P for interaction <0.05). Conclusion: A group-based trajectory model was developed to classify older people into three distinct trajectory groups of the IADL score. The IADL group with increasing risk had a greater risk of MCI than the high-risk IADL group. In the IADL group with increasing risk, city residents of ≥80 years were the most likely to develop MCI.

Construction of immune cell infiltration score model to assess prognostic ability of tumor immune environment in lung adenocarcinoma.

OBJECTIVES: The immune cell infiltration (ICI) in the tumor microenvironment (TME) can provide a reference for prognosis after immunotherapy. We aim to establish an ICI scoring model and evaluate its predictive ability for the immunotherapy efficacy and the prognosis in lung adenocarcinoma (LUAD) patients. METHODS: We developed and analyzed the landscape of infiltrative immune cells based on the CIBERSORT and ESTIMATE algorithms. Then, three clusters of LUAD patients were discerned from TCGA-LUAD and GSE11969 data. Furthermore, two gene clusters were classified based on the PCA. RESULTS: LUAD patients with better prognoses tend to have higher immune checkpoint expression and immune/stromal scores. There is a correlation between TMB and ICI, and their relationship deserves further exploration. Moreover, the early-stage and male patients with high ICI scores have more prolonged survival. CONCLUSIONS: The feasibility of the ICI score model in evaluating prognosis after immune checkpoint therapy for LUAD patients was verified, specifically reflected in the screening of sensitive immune checkpoints as a treatment reference. The scoring system can accurately predict the overall survival of LUAD patients, which has clinical value to monitor disease and evaluate prognosis.

Construction of an in vivo NIR fluorescent probe for revealing the correlation between inflammation and mitochondrial hydrogen sulfide and viscosity.

As an indispensable part of immune response, inflammation plays a critical role in the occurring and advancing of many diseases. It is reported that the emergence of inflammation can be indicated by the change of intracellular viscosity and overexpression of the hydrogen sulfide (H2S) in mitochondria. So far, elucidating the relationship between inflammation and the above parameters remains a challenge due to the lack of validated analytical tools. Herein, a novel dual-function NIR fluorescent probe CMQT with excellent biological compatibility and mitochondrial targeting ability is designed and synthesized by using 7-diethylaminocoumarin and 4-ethylphenolate quinoline acetate through twistable vinyl bonds. With the functional probe, enhanced fluorescent signals at 570 nm and 721 nm are produced in the presence of H2S and changes of viscosity. The CMQT can be applied in living cells and zebrafish, which reveals the increases of mitochondrial H2S and viscosity generated by inflammatory response through dual-channel fluorescence imaging mode. The in vivo dual-functional probe serves as an efficient tool for imaging analysis of H2S and viscosity, and has profound implications for the early diagnosis of inflammatory diseases.

Study on the metabolism profile of flavanomarein in Coreopsis tinctoria Nutt.

Coreopsis tinctoria Nutt. (family Asteraceae) is a popular medicine-food plant, which improves chronic diseases such as hyperlipemia, hypertension, and diabetes. Flavanomarein is the main active component of Coreopsis tinctoria Nutt, in which the blood concentration of volunteers is low and bioavailability is poor. Thus, the understanding of flavanomarein metabolites and metabolic pathways is significant to clarify its effectiveness. This study systematically studied the metabolites of flavanomarein by oral and injection. The biological samples (feces, urine, and plasma) were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry in negative ion mode. The metabolic law of flavanomarein in the liver was further verified by a liver microsomal incubation experiment in vitro. A total of 12 metabolites were identified by oral administration while 15 metabolites were detected by injection. It was shown that metabolic pathways include acetylation, hydroxylation, glucuronidation, methylation, dehydrogenation, and so forth. The liver extraction rate of flavanomarein was 0.08, which means the metabolic stability of flavanomarein is well in rats' liver microsomes. It is a systematic study on the metabolism of flavanomarein and provides a metabolic rationale for further in-depth in vivo biotransformation.

Sleep Factors in Relation to Metabolic Dysfunction-Associated Fatty Liver Disease in Middle-Aged and Elderly Chinese.

CONTEXT: Accumulating evidence implies that sleep disturbance is involved in metabolic disorders. OBJECTIVE: We comprehensively evaluated the association between various dimensions of sleep behaviors and the risk for metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: In this cross-sectional study of 5011 participants with self-reported sleep behaviors and radiologically diagnosed MAFLD, a comprehensive healthy sleep score was generated to evaluate the associations between sleep behaviors and MAFLD risk using multivariate logistic regression adjusting for demographics, lifestyles, medication, and metabolic comorbidities. Furthermore, mediation analysis was utilized to assess the extent to which obesity explains the effect of sleep quality on MAFLD risk. RESULTS: Late bedtime, snoring, and daytime napping for over 30 minutes significantly associated with an increased risk of MAFLD, with odds ratios (OR) of 1.37 (95% CI 1.10, 1.70), 1.59 (95% CI 1.33, 1.91), and 1.17 (95% CI 1.02, 1.35), respectively, after full adjustments including obesity. Participants with disturbance in nighttime sleep and prolonged daytime napping showed the highest risk for MAFLD (OR 2.38, 95% CI 1.73, 3.27). Each additional increase of healthy sleep score was associated with a 16% reduction in MAFLD risk. Further stratified analysis revealed that people with a sedentary lifestyle and central obesity experienced more prominent adverse effects from poor sleep quality than others. Moreover, obesity accounted for only 20.77% of the total effect of sleep quality on MAFLD risk. CONCLUSIONS: Sleep behaviors, both cumulatively and individually, are associated with MAFLD risk. Public health awareness and strategies should be encouraged to curb MAFLD.

Non-linear Associations Between Visceral Adiposity Index and Cardiovascular and Cerebrovascular Diseases: Results From the NHANES (1999-2018).

Objective: To investigate associations between visceral adiposity index (VAI) and cardiovascular and cerebrovascular diseases (CCDs) in the American population from 1999 to 2018. Methods: Data from the National Health and Nutrition Examination Survey (1998-2018) were analyzed in this study. Specifically, VAI scores were calculated using sex-specific equations that incorporate body mass index, waist circumference (WC), high-density lipoprotein (HDL), triglycerides (TG), and cholesterol. Weighted logistic regression analysis was conducted to assess the relationship between VAI tertile and increased risk of CCDs. Restricted cubic splines were used to evaluate the non-linear relationship between VAI and CCDs, such as heart failure, angina, heart attack, stroke, hypertension, and coronary heart disease. Sensitivity analysis was conducted, using VAI quartiles as independent variables. Results: A total of 22,622 subjects aged over 20 years were included. In the fully adjusted model after controlling for covariates, the third VAI tertile was more strongly associated with CCDs than the first VAI tertile, with odds ratio (OR) and 95% confidence interval (95% CI) values for angina of 2.86, 1.68-4.85; heart attack, 1.75, 1.14-2.69; stroke, 2.01, 1.23-3.26; hypertension, 2.28, 1.86-2.78; and coronary heart disease, 1.78, 1.32-2.41; but there was no significant association with heart failure (p > 0.05). Restricted cubic splines revealed parabolic relationships between VAI score and angina (p for non-linear = 0.03), coronary heart disease (p for non-linear = 0.01), and hypertension (p for non-linear < 0.001). Sensitivity analysis indicated that the fourth VAI quartile was more strongly associated with an increased risk of angina (OR = 2.92, 95% CI, 1.49-5.69), hypertension (OR = 2.37, 95% CI, 1.90-2.97), heart attack (OR = 1.77, 95% CI, 1.09-2.88), and coronary heart disease (OR = 1.89, 95% CI, 1.24-2.86) than the first VAI quartile. VAI had superior predictive power for prevalent CCDs than other independent indicators (p < 0.05). Conclusion: Visceral adiposity index score is positively correlated with angina, heart attack, stroke, hypertension, and coronary heart disease, but not heart failure, and the relationships between VAI score and angina, hypertension, and coronary heart disease are non-linear.

Identification of Novel Key Molecular Signatures in the Pathogenesis of Experimental Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a long-term major microvascular complication of uncontrolled hyperglycemia and one of the leading causes of end-stage renal disease (ESDR). The pathogenesis of DKD has not been fully elucidated, and effective therapy to completely halt DKD progression to ESDR is lacking. This study aimed to identify critical molecular signatures and develop novel therapeutic targets for DKD. This study enrolled 10 datasets consisting of 93 renal samples from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). Networkanalyst, Enrichr, STRING, and Cytoscape were used to conduct the differentially expressed genes (DEGs) analysis, pathway enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene screening. The shared DEGs of type 1 diabetic kidney disease (T1DKD) and type 2 diabetic kidney disease (T2DKD) datasets were performed to identify the shared vital pathways and hub genes. Strepotozocin-induced Type 1 diabetes mellitus (T1DM) rat model was prepared, followed by hematoxylin & eosin (HE) staining, and Oil Red O staining to observe the lipid-related morphological changes. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to validate the key DEGs of interest from a meta-analysis in the T1DKD rat. Using meta-analysis, 305 shared DEGs were obtained. Among the top 5 shared DEGs, Tmem43, Mpv17l, and Slco1a1, have not been reported relevant to DKD. Ketone body metabolism ranked in the top 1 in the KEGG enrichment analysis. Coasy, Idi1, Fads2, Acsl3, Oxct1, and Bdh1, as the top 10 down-regulated hub genes, were first identified to be involved in DKD. The qRT-PCR verification results of the novel hub genes were mostly consistent with the meta-analysis. The positive Oil Red O staining showed that the steatosis appeared in tubuloepithelial cells at 6 w after DM onset. Taken together, abnormal ketone body metabolism may be the key factor in the progression of DKD. Targeting metabolic abnormalities of ketone bodies may represent a novel therapeutic strategy for DKD. These identified novel molecular signatures in DKD merit further clinical investigation.

Causal Association Between Tea Consumption and Kidney Function: A Mendelian Randomization Study.

Background: Causal research concerning the consumption of tea and the risk of chronic kidney disease (CKD) is limited. This study identified the potential causal effects of tea intake on CKD, the estimated glomerular filtration rate (eGFR), and albuminuria. Methods: Genome-wide association studies (GWASs) from UK Biobank were able to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea each day. The summary statistics for the kidney function from the CKDGen consortium include 11,765 participants (12,385 cases of CKD) and 54,116 participants for the urinary albumin-to-creatinine ratio who were mostly of European descent. A two-sample Mendelian randomization (MR) analysis was performed to test the relationship between the selected SNPs and the risk of CKD. Results: A total of 2,672 SNPs associated with tea consumption (p < 5 × 10-8) were found, 45 of which were independent and usable in CKDGen. Drinking more cups of tea per day indicates a protective effect for CKD G3-G5 [odds ratio (OR) = 0.803; p = 0.004] and increases eGFR (ß = 0.019 log ml/min/1.73 m2 per cup per day; p = 2.21 × 10-5). Excluding two SNPs responsible for directional heterogeneity (Cochran Q p = 0.02), a high consumption of tea was also negatively correlated with a lower risk of albuminuria (OR = 0.758; p = 0.002). Conclusion: From the perspective of genes, causal relationships exist between daily extra cup of tea and the reduced risk of CKD and albuminuria and increased eGFR.

Prevalence and risk factors of metabolic associated fatty liver disease in the contemporary South China population.

BACKGROUND: As a newly proposed diagnosis, data on the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rare. We aimed to assess the prevalence and risk factors of MAFLD using new definition in the contemporary South China population. METHODS: In this population based, cross sectional study, a total of 5377 participants aged 30-79 years old were recruited from the South China between 2018 and 2019. MAFLD was diagnosed in subjects who have both hepatic steatosis and metabolic disorders according to the newly international expert consensus. The total prevalence of MAFLD and prevalence by sex and age was estimated. Demographic characteristics, history of disease, and lifestyle were recorded by participants on a questionnaire. Abdominal ultrasonography was performed and evaluated by experienced sonographers. Multivariable logistic regression was used to calculate the odds ratios (ORs) of MAFLD. RESULTS: Overall prevalence of MAFLD was 29.2% (95% confidence interval [CI] 28.0% to 30.5%). Prevalence was higher in women (31.7%) than in men (25.5%; p < 0.001 for sex difference) and in subjects aged 50 years or older (30.7%) than in those aged 30-49 years (19.8%; p < 0.001 for age difference). In participants diagnosed with MAFLD, the prevalence of overweight/obesity was up to 90.5%, type 2 diabetes (T2DM) and metabolic dysregulation were 25.0% and 62.2%, respectively. Risk factors for MAFLD included overweight/obesity (OR = 4.67; 95% CI, 3.76-5.83), T2DM (OR = 2.41, 95% CI, 1.68-3.47), hypertriglyceridemia (OR = 2.42, 95% CI, 2.03-2.87), high school education (OR = 1.50, 95% CI, 1.23-1.82), high income (OR = 1.22, 95% CI, 1.05-1.42). A lower risk of MAFLD was associated with high physical activity equivalent (OR = 0.71, 95% CI, 0.60-0.85). A U-shaped association of frequency of soups and ORs of MAFLD was found, the adjusted ORs (95% CI) of lower and higher frequency of soups were 1.58 (1.32-1.89) and 1.36 (1.13-1.63), respectively. CONCLUSIONS: Our results showed a high prevalence of MAFLD in the general adult population in South China. Obesity has the greatest impact on MAFLD, physical activity and moderate consumption of soups might be the potential protective factors of MAFLD.

Association Between Drinking Water Sources and Osteoarthritis Incidence in Chinese Elderly Population: National Population-Based Cohort Study.

BACKGROUND: The elderly is a vulnerable group susceptible to toxic environmental factors; however, the association between unsafe water and osteoarthritis (OA) incident among this population is poorly investigated. This study aimed to examine the effects of drinking water sources on OA risk in the Chinese elderly population. METHODS: Data were obtained from the China Longitudinal Healthy Longevity Survey to perform a 16-year longitudinal study. All participants aged ≥65 years at baseline were potentially eligible. Information on drinking water sources was recorded via a structured questionnaire. The water source was classified as well, surface, spring, or tap. OA was selected as the health outcome. Cox proportional hazard models, adjusted socio-demographics, lifestyle, and chronic disease were used to estimate the hazard ratio (HR) for OA. Subgroup analyses were performed to assess the potential interactive effect. RESULTS: A total of 12,543 participants were included. With restriction to the longest follow-up time, the mean survival time of follow-up was 14.56 years. Among the cohort members, 1,585 members suffered from OA. In the full model, drinking from well water and spring water was associated with a higher risk of OA compared with drinking from tap water (HR: 1.37, 95% CI: 1.22-1.54; HR: 1.34, 95% CI: 1.03-1.74). Except for age, the effects of modifications from socioeconomic status, lifestyles, and health conditions were non-significant (p for interaction <0.05). After multiple imputations for missing data and excluding deaths in the first year of follow-up and participants with a history of the disease and using the Shared-frailty Cox model, sensitivity analysis indicated a robust association between the drinking water source and OA incidence. CONCLUSION: Drinking tap water was associated with a low risk of OA among older adults in China. The use of clean water sources as a marker of decreased OA and arthritis risks must be revisited in low- and middle-income countries.