H3K27 Acetylation-Activated GLDC Accelerated the Advancement of Oral Squamous Cell Carcinoma by Suppressing the p53 Signaling Pathway.

Glycine decarboxylase (GLDC) has been identified to be dysregulated and plays pivotal roles in various cancers. Besides, studies have suggested that GLDC expression is elevated in oral squamous cell carcinoma (OSCC) and associated with a worse prognosis, but the precise role and molecular mechanism of GLDC in OSCC remain unexplored. The current study first confirmed the high expression of GLDC in OSCC and its correlation with worse survival in patients with OSCC. By knocking down GLDC, it was discovered that the growth and colony formation of OSCC cells, as well as the development of xenograft tumors, were effectively suppressed. In addition, GLDC deficiency inhibited the migration and invasion of OSCC cells in vitro through regulating EMT markers and attenuated lung metastasis in vivo. Mechanistically, GLDC was found to affect the activity of the p53 signaling pathway. GLDC depletion retarded the progression of OSCC by activating the p53 signaling pathway. Moreover, p300 co-functioned with TFAP2A to induce acetylation of GLDC, which resulted in the upregulation of GLDC in OSCC. To conclude, acetylation-induced GLDC upregulation facilitated the tumorigenesis and metastasis of OSCC by its inhibition of the activity of the p53 signaling pathway.

Association between ambient temperature and cause-specific mortality: An individual-level case-crossover study in Suzhou, China.

The changing climate poses a growing challenge to the population health. The objective of this study was to assess the association between ambient temperature and cause-specific mortality in Suzhou. Based on the non-accidental mortality data collected during 2008-2022 in Suzhou, China, this study utilized an individual-level case-crossover design to evaluate the associations of temperature with cause-specific mortality. We applied a distributed lag nonlinear model with a maximum lag of 14 days to account for lag effects. Mortality risk due to extreme cold (<2.5th percentile) and extreme heat (>97.5th percentile) was analyzed. A total of 634,530 non-accidental deaths were analyzed in this study. An inverse J-shaped exposure-response relationship was observed between ambient temperature and non-accidental mortality, with the minimum mortality temperature (MMT) at 29.1℃. The relative risk (RR) of mortality associated with extreme cold (2.5th percentile) was 1.37 [95 % confidence interval (CI): 1.30, 1.44], higher than estimate of 1.09 (95 %CI: 1.07, 1.11) for extreme heat (97.5th percentile) relative to the MMT. Heat effect lasted for 2-3 days, while cold effect could persist for almost 14 days. Higher mortality risk estimates were observed for cardiorespiratory deaths compared to total deaths, with statistically significant between-group differences. Consequently, this study provides first-hand evidence on the associations between ambient temperatures and mortality risks from various causes, which could help local government and policy-makers in designing targeted strategies and public health measures against the menace of climate change.

Correlates of feeding difficulties among children of Chinese transgender parents.

Background: Ensuring proper early feeding for young children is crucial, as encountering feeding difficulties (FD) during this stage can give rise to a cascade of health problems, the repercussions of which may endure into late childhood and adolescence. Children raised by transgender parents may be at risk of encountering FD, however, there is no research conducted on Chinese transgender families. Methods: We designed a cross-sectional survey in which the rate of FD and its influencing factors were investigated among transgender parents in China. A total of 446 Chinese transgender parents (average age 30.39 years) were included in the analysis. Logistic regression models were applied to investigate the influencing factors of FD among children of transgender parents. We also established structural equation modeling (SEM) to explore the possible pathways among these factors and FD. Results: The rate of FD in children of Chinese transgender parents is 55.4%, with 34.5% having severe FD. Coming out after having a child (AOR = 2.26, 95%CI = 1.33 ∼ 3.91), family violence (AOR = 1.06, 95%CI = 1.04 ∼ 1.09), partner violence (AOR = 1.11, 95%CI = 1.08 ∼ 1.15), no feeding education (accepting feeding education: AOR = 0.43, 95%CI = 0.25 ∼ 0.74), being discriminated during seeking of childbearing health care (AOR = 1.99, 95%CI = 1.3 ∼ 3.05), and poor relationship with partner (fair: AOR = 0.09, 95%CI = 0.03 ∼ 0.22; good: AOR = 0.06, 95%CI = 0.02 ∼ 0.15) are significantly associated with higher FD. Furthermore, through the pathway analysis, the indirect effects of education level (ß=-0.151), feeding education (ß = 0.145), and relationship with partner (ß=-0.196) on FD are observed. Conclusions: Children of Chinese transgender parents showed a high FD rate. It is crucial to help build a better family and social environment for transgender families to reduce the FD and improve children's and adolescents' health.

The impact of the COVID-19 pandemic on dietary behaviors among school-age children, adolescents, and young adults: a systematic review and meta-analysis.

CONTEXT: The COVID-19 pandemic has had a global impact on food security and nutrition, both in the short and long term. The influence on school-age children, adolescents, and young adults may be particularly significant and long-lasting. OBJECTIVE: This systematic review and meta-analysis aimed to quantify the impact of the COVID-19 pandemic on dietary habits among school-age children, adolescents, and young adults worldwide. DATA SOURCES: PubMed, Web of Science, and Embase were searched from inception to October 5, 2023. DATA EXTRACTION: We included observational studies published in English that reported dietary quality scores and dietary intake quantities during and before the COVID-19 pandemic among school-age children, adolescents, and young adults. We included a total of 22 cohort studies and 20 cross-sectional studies of high or moderate quality. DATA ANALYSIS: We conducted a meta-analysis, expressing dietary quality scores and dietary intake quantities as standardized mean differences (SMD) with 95% confidence intervals (CIs). For studies with low heterogeneity, we used a fixed-effects model; otherwise, we applied a random-effects model. The Newcastle-Ottawa Scale was employed by 2 reviewers independently to evaluate methodological quality. The analysis indicated that, overall, juice intake increased (SMD = 0.12, 95% CI: 0.04 to 0.20), while alcohol consumption reduced during the COVID-19 pandemic (SMD = -0.28, 95% CI: -0.47 to -0.08). However, the age-stratified results varied. Among school-age children, intake of fruit, dairy products, sugar, and juice increased. Adolescents showed an increase in meal frequency and vegetable intake. Young adults showed reduced carbohydrate and alcohol intakes, while protein and dairy product intakes increased, based on limited included studies. CONCLUSION: Dietary changes in school-age children from before to during the pandemic were mixed, while dietary behavior changes in adolescents and young adults tended to be more positive. Considering the lasting effects of negative dietary behaviors, attention should be given to addressing the increased sugar and juice intakes. It is also crucial that caregivers and researchers monitor whether positive dietary behaviors will rebound after returning to normal study and life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023420923.

Upregulation of LY6K induced by FTO-mediated demethylation promotes the tumorigenesis and metastasis of oral squamous cell carcinoma via CAV-1-mediated ERK1/2 signaling activation.

Lymphocyte antigen 6 complex locus K (LY6K) has been demonstrated to play a significant role in cancers and identified as a therapeutic biomarker for head and neck squamous cell carcinoma. However, the role of LY6K in oral squamous cell carcinoma (OSCC) has not been explored. The current study discovered that LY6K was aberrantly upregulated in OSCC cell lines and tissues and that high LY6K expression significantly correlated with poorer survival of OSCC patients. Through stable knockdown of LY6K, we found that the growth, colony formation, migration, and invasion of OSCC cells were substantially suppressed. In addition, tumor growth and lung metastasis in vivo were effectively inhibited by LY6K depletion. Mechanically, LY6K binds with CAV-1 and activates CAV-1-mediated MAPK/ERK signaling to exert its oncogenic effects on OSCC. In addition, LY6K expression in OSCC was discovered to be regulated by FTO-mediated RNA N6-methyladenosine (m6A) modification in an IGF2BP1-dependent manner. Generally, LY6K expression was upregulated by FTO-mediated demethylation in OSCC, which promoted the tumorigenesis and metastasis of OSCC via activating the CAV-1-mediated ERK1/2 signaling pathway.

Sarcopenic obesity is part of obesity paradox in dementia development: evidence from a population-based cohort study.

BACKGROUND: Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset. METHODS: We included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined. RESULTS: Obese women with high PRS had a decreased risk (HR = 0.855 [0.761-0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045-1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HRwomen = 1.323 [1.064-1.644]; HRmen = 2.144 [1.753-2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HRwomen = 1.679 [1.355-2.081]; HRmen = 2.069 [1.656-2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HRwomen = 1.424 [1.227-1.653]; HRmen = 1.989 [1.702-2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases. CONCLUSIONS: Sarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background.

Distributed genotyping and clustering of Neisseria strains reveal continual emergence of epidemic meningococcus over a century.

Core genome multilocus sequence typing (cgMLST) is commonly used to classify bacterial strains into different types, for taxonomical and epidemiological applications. However, cgMLST schemes require central databases for the nomenclature of new alleles and sequence types, which must be synchronized worldwide and involve increasingly intensive calculation and storage demands. Here, we describe a distributed cgMLST (dcgMLST) scheme that does not require a central database of allelic sequences and apply it to study evolutionary patterns of epidemic and endemic strains of the genus Neisseria. We classify 69,994 worldwide Neisseria strains into multi-level clusters that assign species, lineages, and local disease outbreaks. We divide Neisseria meningitidis into 168 endemic lineages and three epidemic lineages responsible for at least 9 epidemics in the past century. According to our analyses, the epidemic and endemic lineages experienced very different population dynamics in the past 100 years. Epidemic lineages repetitively emerged from endemic lineages, disseminated worldwide, and apparently disappeared rapidly afterward. We propose a stepwise model for the evolutionary trajectory of epidemic lineages in Neisseria, and expect that the development of similar dcgMLST schemes will facilitate epidemiological studies of other bacterial pathogens.

Functional proteins in breast milk and their correlation with the development of the infant gut microbiota: a study of mother-infant pairs.

Introduction: Proteins in breast milk play an important role in the growth and development of infants. This study aims to explore the correlation between functional proteins in breast milk and the infant gut microbiota. Methods: Twenty-three mothers and their infants were enrolled and breast milk samples and infant fecal samples were collected. Breast milk protein content was determined by UPLC-MS/MS, and 16S rRNA sequencing was employed to analyze the gut microbiota of infant. Results: The results indicated that the secretory immunoglobulin A (sIgA) content in breast milk was positively correlated with the abundance of Veillonella parvula. The κ-casein content was positively correlated with the abundance of Clostridium butyricum. The osteopontin (OPN) and lactalbumin contents were positively correlated with the abundance of Parabacteroides distasonis at 42 days. Functional pathway analysis showed that the OPN and κ-casein contents in breast milk were significantly correlated with amino acid, pyruvate, propionic acid, linoleic acid, and alpha-linolenic acid metabolic pathways in early life. Discussion: The results of this study suggest that specific proteins in breast milk can influence the abundance of certain gut microbes in infants, playing an important role in early immune and metabolic development.

Effect and mechanism of HMG-CoA reductase inhibitor on the improvement of elderly essential hypertension-induced vascular endothelial function impairment based on the JAK/STAT pathway.

OBJECTIVE: Our research was designed to figure out the influence and mechanism of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on the improvement of elderly essential hypertension-induced vascular endothelial function impairment based on the JAK/STAT pathway. METHODS: Eighty-six elderly patients with essential hypertension were randomized into a control group (oral Amlodipine Besylate Tablets) and an observation group (oral Amlodipine Besylate Tablets + HMG-CoA reductase inhibitor atorvastatin calcium). Patients in both groups were treated with the drug for 12 weeks. Blood pressure, serum levels of inflammatory factors, and vascular endothelial function indicators, and levels of blood lipids were measured. The modeled rats were treated with atorvastatin calcium and a JAK/STAT pathway inhibitor (AG490), and the levels of cardiac function-related indices, left ventricular mass index, lipid levels, serum inflammatory factors and vascular endothelial function-related indices were detected in each group. RESULTS: HMG-CoA reductase inhibitor improved blood pressure levels, lipid levels, serum inflammatory factor levels and cardiac function in elderly patients with essential hypertension. Both HMG-CoA reductase inhibitor and AG490 improved blood pressure levels, lipid levels, serum inflammatory factor levels and cardiac function in SHR rats. Both HMG-CoA reductase inhibitor and AG490 decreased p-JAK2/JAK2 and p-STAT3/STAT3 expression levels. CONCLUSION: Our study demonstrates that HMG-CoA reductase inhibitor improves elderly essential hypertension-induced vascular endothelial function impairment by blocking the JAK/STAT pathway.

Rates of breastfeeding or chestfeeding and influencing factors among transgender and gender-diverse parents: a cross sectional study.

Background: Breastfeeding is essential for the growth and development of all infants. Despite the large transgender and gender-diverse population size, there is no comprehensive research of breastfeeding or chestfeeding practices in this group. This study was designed aimed to investigate the status of breastfeeding or chestfeeding practices in transgender and gender-diverse parents and to explore the possible influencing factors. Methods: A cross-sectional study was conducted between January 27 2022 and February 15 2022 online in China. A representative sample of 647 transgender and gender-diverse parents was enrolled. Validated questionnaires were used to investigate breastfeeding or chestfeeding practices and its associated factors, including physical factors, psychological factors and socio-environmental factors. Findings: The exclusive breastfeeding or chestfeeding rate was 33.5% (214) and only 41.3% (244) of infants could be continuously fed until 6 months. Accepting hormonotherapy after having this child (adjusted odds ratio (AOR) = 1.664, 95% confidential interval (CI) = 1.014∼2.738) and receiving feeding education (AOR = 2.161, 95% CI = 1.363∼3.508) were associated with a higher exclusive breastfeeding or chestfeeding rate, while higher gender dysphoria scores (37-47: AOR = 0.549, 95% CI = 0.364∼0.827; >47: AOR = 0.474, 95% CI = 0.286∼0.778), experiencing family violence (15-35: AOR = 0.388, 95% CI = 0.257∼0.583; >35: AOR = 0.335; 95% CI = 0.203∼0.545), experiencing partner violence (≥30: AOR = 0.541, 95% CI = 0.334∼0.867), using artificial insemination (AOR = 0.269, 95% CI = 0.12∼0.541), or surrogacy (AOR = 0.406, 95% CI = 0.199∼0.776) and being discriminated against during seeking of childbearing health care (AOR = 0.402, 95% CI = 0.28∼0.576), are significantly associated with a lower exclusive breastfeeding or chestfeeding rate. Participants who had feeding education were more likely to feed their child with human milk as the first food intake (AOR = 1.644, 95% CI = 1.015∼2.632), while those who had suffered from family violence (>35: AOR = 0.47; 95% CI = 0.259∼0.84), discrimination (AOR = 0.457, 95% CI = 0.284∼0.721) and chose artificial insemination (AOR = 0.304, 95% CI = 0.168∼0.56) or surrogacy (AOR = 0.264, 95% CI = 0.144∼0.489), were less likely to give their child human milk as first food intake. Besides, discrimination is also related to a shorter breastfeeding or chestfeeding duration (AOR = 0.535, 95% CI = 0.375∼0.761). Interpretation: Breastfeeding or chestfeeding are neglected health problems in the transgender and gender-diverse population and many socio-demographic factors, transgender and gender-diverse-related factors, and family environment are correlated with it. Better social and family support is necessary to improve breastfeeding or chestfeeding practices. Funding: There are no funding sources to declare.

The Association between Sugar-Sweetened Beverages and Male Pattern Hair Loss in Young Men.

We performed this study to investigate the association between sugar-sweetened beverage (SSB) consumption and male pattern hair loss (MPHL) in young men. We conducted this cross-sectional study from January to April 2022 in mainland China. Young people aged 18-45 years (n = 1951) were recruited from 31 provinces in China. We used a self-reported online survey for data collection. We explored the associations between the amount/frequency of SSB consumption and MPHL by using a binary logistic regression model, with adjustments for sociodemographic, hair status, dietary intake, lifestyle, and psychological factors. Among the 1028 participants (27.8 ± 7.2 years) in the final analysis, we found that high SSB consumption is associated with a higher risk of MPHL. We recommend more support to decrease SSB consumption among young people to minimize negative health outcomes.

Selenium Supplementation Protects Against Arsenic-Trioxide-Induced Cardiotoxicity Via Reducing Oxidative Stress and Inflammation Through Increasing NAD+ Pool.

Arsenic is an environmental contaminant, and accumulating evidence has indicated that exposure to arsenic can cause various diseases, especially cardiotoxicity. Selenium (Se) exerts a vital role in the regulation of multiple physiological activities. Recently, several studies highlighted that Se treatment can effectively antagonize the toxic effects induced by arsenic. However, the exact underlying effect and mechanism of Se on Arsenic-induced cardiotoxicity has not been explored. In the current study, the arsenic trioxide (ATO)-triggered heart damage mice model was used to explore whether Se exerts protective roles in ATO-related cardiotoxicity and its potential mechanism. Our data showed that Se treatment significantly alleviated ATO-mediated cardiotoxicity evidenced by increased weight, decreased myocardial damage markers, and improved heart functions in mice. Furthermore, we demonstrated that Se remarkably inhibited ATO-mediated oxidative stress and inflammatory responses in heart tissues. Mechanistically, we showed that Se upregulated the levels of NAD+ in cardiomyocytes of the mice challenged by ATO, and this effect involved in the activation of the NAD+ biosynthesis through the salvage pathway. Collectively, our findings demonstrated that Se protected against ATO-mediated cardiotoxicity by antioxidant and anti-inflammatory effects via increasing the NAD+ pool in mice.

Pediatric body mass index trajectories and the risk of hypertension among adolescents in China: a retrospective cohort study.

BACKGROUND: The impact of pediatric body mass index (BMI) trajectories on the risk of adolescent hypertension (HTN) determined by three separate visits remains unclear. This longitudinal study aims to identify potential pediatric sex-specific BMI trajectories and to assess their associations with HTN and HTN subtypes. METHODS: Based on the Health Promotion Program for Children and Adolescents (HPPCA) in Suzhou, China, a total of 24,426 participants who had initial normal blood pressure (BP) and had at least four BMI measurements during 2012-2020 were included. HTN was defined as simultaneously having three separate visits of elevated BP in 2020. Latent class growth models were used to explore sex-specific BMI trajectories, whose associations with HTN and HTN subtypes were further examined by logistic regression. RESULTS: The incidence of HTN determined through three separate visits was 3.34%. Four trajectories were identified for both sexes: low BMI increasing, medium BMI increasing, high BMI increasing, and highest BMI increasing. Compared to the medium BMI increasing group, the odds ratio (95% confidential interval) for developing adolescent HTN of the low, high, and highest BMI increasing groups among boys were 0.54 (0.39, 0.75), 1.90 (1.44, 2.51), and 2.89 (1.90, 4.39), respectively; and the corresponding values for girls were 0.66 (0.48, 0.90), 2.30 (1.72, 3.09), and 4.71 (3.06, 7.26). Similar gradually elevated associations between different trajectories with isolated systolic hypertension, systolic and diastolic hypertension were observed. CONCLUSION: Current results emphasized the adverse effects of stable high BMI on HTN and the benefits of maintaining normal weight throughout childhood.

Comparisons of tri-ponderal mass index and body mass index in discriminating hypertension at three separate visits in adolescents: A retrospective cohort study.

Objective: To estimate whether the new obesity indicator tri-ponderal mass index (TMI) has a better capacity to predict adolescent hypertension (HTN) and HTN subtypes at three separate blood pressure (BP) visits than the conventionally used body mass index (BMI). Methods: A total of 36,950 adolescents who had initial normal BP from 2012 to 2019 were included in Suzhou, China. HTN was defined as having three separate visits of elevated BP in 2020. The area under the receiver-operating characteristic curve (AUC), false-positive rate, false-negative rate, total misclassification rates, net reclassification improvement (NRI), and integrated discrimination improvement were calculated to compare the discriminative ability of HTN between BMI and TMI. Results: TMI had better predictive abilities than BMI among all of the participants when predicting HTN (difference in AUC = 0.019, 95% CI = 0.007-0.031; NRI = 0.067, 95% CI = 0.008-0.127) and isolated systolic hypertension (difference in AUC = 0.021, 95% CI = 0.005-0.036; NRI = 0.106, 95% CI = 0.029-0.183). The difference in prediction abilities between BMI and TMI was more obvious in the subgroup of age ≥16. Also, TMI outperformed BMI in predicting adolescent HTN in girls but not in boys. Conclusion: Compared with BMI, TMI may have a better predictive capacity for HTN, particularly in girls and older adolescents. TMI has the potential to be used as an effective predictor for HTN in clinic practice. Further studies are needed to verify the utility of TMI.

Prevalence of hypertension and related risk factors among children and adolescents at three separate visits: A large school-based study in China.

Objective: We aimed to demonstrate characteristics of hypertension at three separate visits and its risk factors among children and adolescents based on a large school-based study in China. Materials and methods: Based on a large-scale ongoing monitoring program conducted in Suzhou, China, 59,679 children and adolescents aged 7-17 years from 60 public schools were enrolled during 2020 to 2021. Height, weight, and blood pressure (BP) were measured. Additional BP would be measured for hypertensive students at least 2 weeks later. Confirmed hypertension was defined as simultaneously BP meeting above or equal to 95th percentile for age, sex, and height at three separate visits. Odds ratio (ORs), and 95% CIs were calculated by logistic regression to identify risk factors for hypertension. Results: Prevalence of hypertension at three separate visits were 20.4, 6.3, and 3.1%, respectively. Prevalence of confirmed isolated systolic hypertension, isolated diastolic hypertension, and systolic and diastolic hypertension were 1.9, 0.3, and 0.9%, respectively. Hypertension prevalence for stages 1 and 2 were 2.6 and 0.6%. Different hypertension prevalence were found among various age and gender groups. Boys [OR, 1.137 (95% CI, 1.033-1.251)], high age [OR, 3.326 (95% CI, 2.950-3.751)], urban residents [OR, 1.579 (95% CI, 1.417-1.760)], high-socioeconomic status [OR, 1.156 (95% CI, 1.039-1.286)] and body mass index category including overweight [1.883 (95% CI, 1.665-2.129)], obesity [4.049 (95% CI, 3.625-4.523)], and thinness [OR, 0.457 (95% CI, 0.306-0.683)] were associated with confirmed hypertension. Conclusion: A single BP measurement would overestimate hypertension prevalence, about 3% Chinese children were hypertensive, early, and effective intervention around risk factors for hypertension should be taken.

Association between dairy consumption and the risk of diabetes: A prospective cohort study from the China Health and Nutrition Survey.

Diet is closely related to the risk of diabetes; yet the relationship between dairy consumption and the risk of diabetes is unclear with conflicting evidence from previous studies. This study used data from the Chinese Health and Nutrition Survey to investigate the association between dairy consumption and diabetes. A total of 15,512 adults were included; dairy consumption at each survey was assessed by the 3-day 24-h recall and weighed food record methods, and diabetes occurrence was derived from self-reported information. The association between dairy consumption and diabetes was explored using Cox regression and further stratified with BMI and energy intake. Results indicated that 12,368 (79.7%) participants had no dairy consumption, while 2,179 (14.0%) and 947 (6.1%) consumed dairy at 0.1-100 and >100 g/day, respectively. After adjusting for potential confounders, dairy consumption of 0.1-100 g/day was associated with lower risk of diabetes in all participants (HR 0.53, 95% CI:0.38 -0.74; P < 0.001) and males (HR 0.50, 95% CI: 0.31-0.80; P = 0.004). According to the restricted cubic splines (RCS), the protective effect on diabetes was significant in the total population with dairy consumption ranging from 25 to 65 g/day (HR <1, P = 0.025). In the stratified analysis, consuming 30-80 g/day was associated with reduced diabetes risk among the ≤ 2,000 kcal/day energy intake group (HR <1, P = 0.023). In conclusion, dairy consumption was inversely associated with a reduced diabetes risk in Chinese population. Further studies are required to examine the optimal level of dairy consumption for preventing diabetes in the Chinese population.

Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission.

ABSTRACT: Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H2S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H2S ameliorates transforming growth factor-ß1 (TGF-ß1)-induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H2S treatment dramatically suppressed TGF-ß1-induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H2S reversed TGF-ß1-induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1-dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H2S attenuates TGF-ß1-induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1-dependent fashion.

Selenium Attenuates Doxorubicin-Induced Cardiotoxicity Through Nrf2-NLRP3 Pathway.

Selenium (Se), an essential nutrient for humans, has been reported to possess cardioprotective effect. However, the protective effects of Se against doxorubicin (DOX)-induced cardiotoxicity and the underlying mechanism are rarely reported. In this study, we sought to explore whether Se protected against DOX-induced cardiotoxicity by inhibiting Nrf2-NLRP3 pathway. We found that Se treatment effectively alleviated DOX-induced myocardial dysfunctions, decreasing plasma markers associated with myocardial injury. Moreover, Se treatment significantly inhibited DOX-induced oxidative damages and pro-inflammatory cytokine expression in heart tissues. Furthermore, Se treatment markedly promoted the expression of Nrf2 and prevented the activation of NLRP3 inflammasome. Importantly, suppression of Nrf2 abolished the cardioprotective effects of Se and diminished the inhibition of Se on NLRP3 inflammasome. Collectively, our study demonstrated that Se might protect against DOX-induced cardiotoxicity via regulating Nrf2-NLRP3 pathway. Se supplementation may be a potential therapeutic strategy to protect against DOX-induced cardiac injury.

Comparison of China Reference with Different National and International References: The Prevalence of High Blood Pressure in 695,302 Children and Adolescents in a Metropolis of Yangtze River Delta, China.

OBJECTIVES: This study aimed to compare performances of China reference and different national references on high blood pressure (HBP). METHODS: A cross-sectional study including 695,302 children and adolescents aged 7 to 17 years in Suzhou, China, was conducted to determine the prevalence of HBP based on U.S., international, Europe, and China references in 2016. RESULTS: Different percentiles of height and blood pressure were found among four references. Referring to U.S. reference, the prevalence of HBP was the highest with 26.0%, followed by International reference with 20.0%, Europe reference with 19.5%, and China reference with 19.2%. McNemar tests indicated statistically significant differences between HBP prevalence comparing China reference with the other 3 references (P < 0.001). The area under the curve was 0.947, 0.851, and 0.949 for U.S., international, and Europe reference, respectively. U.S. reference showed the highest sensitivity (98.2%), but the lowest specificity (91.2%), and Europe reference showed the highest kappa value (0.893). CONCLUSIONS: The prevalence of HBP varied among these four references, and the appropriate choice of reference would be important to recognize high-risk children and judge the trends of HBP prevalence in the targeted population.

[Effects of extracellular matrix PDMS stiffness on proliferation and osteogenic differentiation of dental pulp stem cells].

PURPOSE: To investigate the effects of extracellular matrix stiffness on proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) in polydimethylsiloxane (PDMS)-based cell culture substrate model. METHODS: The premolars removed during orthodontic treatment in Changzhou NO.2 People's Hospital were collected for DPSCs culture. PDMS matrix membranes were prepared, and divided into three groups according to the different stiffness degrees, group A (binder/hardener: 10∶1; 135 kPa), group B (binder/hardener: 20∶1; 54 kPa), and group C (binder/hardener: 30∶1; 16 kPa). Group free from PDMS was set as control group. Thereafter, DPSCs cells were cultured on PDMS matrix, and various indexes were detected. The proliferation rate of DPSCs was detected by CCK-8, the osteogenic differentiation of DPSCs was detected by alizarin red staining, and the protein expression levels of osteocalcin(OCN), RUNX2, Wnt1 and ß-catenin were detected by Western blot. The data were processed with SPSS 22.0 software package. RESULTS: Alizarin red staining showed that DPSCs cells in group A had obvious morphological changes, and the cell arrangement showed obvious orientation, its morphology gradually changed from polygon and spindle shape to square shape, and calcified nodules were also observed. The number of calcified nodules among four groups were the most in the group A, followed by group B and group C, which was the lowest in control group, with significant difference (P<0.05). The cell proliferation rate and the expression of OCN, RUNX2, Wnt1 and ß-catenin were the highest in group A, followed by group B and group C, which was the lowest in control group, with significant difference(P<0.05). CONCLUSIONS: The extracellular matrix with high stiffness may promote the proliferation and osteogenic differentiation of DPSCs by activating Wnt/ß-catenin signaling pathway, which may provide a theoretical basis for periodontal tissue engineering.