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Objective To investigate the effect of Nutlin-3a, a mouse double minute 2 homolog (MDM2) inhibitor, on lipid metabolism of mouse adipose. Methods High-fat diet-induced obesity (DIO) C57BL/6J mice were randomly divided into a control group injected with DMSO and an experimental group injected with Nutlin-3a. Then we conducted glucose tolerance (GTT) and insulin tolerance (ITT) tests. The epididymal white adipose tissue (eWAT), inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT) of animals were isolated and microscopy of WATs with hematoxylin-eosin (HE) staining was performed to observe the morphological changes of adipocytes. The expression of lipid metabolism related gene cell death-inducing DFF45-like effector C (CIDEC) in eWAT were detected by qPCR and Western blot. Results Compared with the control group, Nutlin-3a was found to promote the body weight (P＜0.001),but no effect on glucose tolerance and insulin sensitivity in DIO mice. Nutlin-3a treatment decreased the size of adipocytes and fat deposition in adipose tissue and downregulated the mRNA and protein levels of CIDEC in eWAT. Conclusions Nutlin-3a inhibits the formation of lipid droplets by downregulating expression of CIDEC in white adipose tissue.

Objective To investigate the role and regulatory mechanism of stress-inducing protein 1(SESN1) in liver gluconeogenesis of fasting mice. Methods RT-qPCR was used to detect mRNA expression of SESN1 in liver tissues of C57BL/6J mice and primary mouse hepatocytes treated with forskolin (Fsk) and dexamethasone(Dex). HepG2 cells were transfected with plasmids and the effects of SESN1 overexpression on mRNA expression of gluconeogenesis related genes PGC-1α, PEPCK and G6Pase was detected by RT-qPCR. The effect of SESN1 on the promoter activity of PGC-1α in HepG2 cells was studied using a dual luciferase reporter system. The effect of SESN1 on PGC-1α deacetylation was detected by overexpression of SESN1 and inhibition of SIRT1 expression.By knocking down SIRT1 expression, we detected whether it mediated the changes in mRNA levels of SESN1 induced gluconeogenesis related genes. Results The mRNA expression of SESN1 was significantly increased in liver tissues of starved C57BL/6J mice and in primary hepatocytes treated with Fsk and Dex(P＜0.001). Over-expression of SESN1 in HepG2 cells promoted mRNA expression of PGC-1α, PEPCK and G6Pase(P＜0.001) and promoter activity of PGC-1α(P＜0.001). Over-expression of SESN1 decreased the acetylation level of PGC-1α in primary hepatocytes.Sirt family inhibitors NAM and shRNA adenovirus interfered with SIRT1 expression respectively, and antagonized the deacetylation effect of SESN1 on PGC-1α. The expression of PGC-1α, PEPCK and G6Pase induced by SIRT1 was also significantly impaired(P＜0.000 1). Conclusions SESN1 regulates liver gluconeogenesis in mice with a SIRT1-dependent mechanism.

BackgroundFood and nutrition literacy (FNL) plays an important role in young adults’ dietary habits and nutrition. This study aimed to investigate FNL status and its associated factors among young adults aged 15–44 years in Shenzhen.MethodsA cross-sectional survey of 5,390 participants was conducted in June 2021. FNL was measured using the Food and Nutrition Literacy Questionnaire for Chinese Adults (FNLQ). A generalized linear model was employed to analyze the factors associated with FNL.ResultsThe median FNL score (total score = 100) was 68.00, which was below the adequate level of 80. FNL was divided into the two different domains of knowledge and skills, with significantly different scoring rate of 85.30 and 67.77%, respectively. The overall proportion of respondents with adequate FNL was 19.52%. The FNL score was significantly higher among the participants who were female (β = 2.665; 95% confidence interval [CI]: 2.031–3.299) and with higher education levels (β ranging from 5.632 [CI: 3.845–7.419] to 10.756 [CI: 8.973–12.538]), healthcare-related work experience (β = 4.197; CI: 3.557–4.837) and a higher economic status (β ranging from 0.753 [CI: 0.079–1.426] to 6.217 [CI: 5.208–7.227]). Those who were divorced or with an unknown marital status (β = −8.438; CI: −9.701, −7.175), abnormal body mass index (thin [β = −2.115; CI: −3.063, −1.166], overweight [β = −1.427; CI: −2.254, −0.600]), and suffering from chronic diseases (single disease [β = −3.483; CI: −4.485, −2.480], multimorbidity [β = −5.119; CI: −5.912, −4.327]) had significantly lower FNL scores.ConclusionGenerally, the level of FNL among young adults in Shenzhen, China, was relatively low. Thus, nutrition education programs targeted at promoting improved FNL status call for additional emphasis, especially in subgroups with lower scores.

Background There are few studies on the relationship between sleep time and falls at present, and the research results are inconsistent. Objective To explore the relationship between sleeping time and falls in middle-aged and elderly residents in China, and to provide reference for preventing falls in this population. Methods The study based on the data from China Health and Retirement Longitudinal Survey (CHARLS) data in 2015. 18 181 subjects aged ≥45 years with complete key data were included. Collect the indicators of the middle-aged and old people in the past two years, such as falls and medical treatment, sleep time, demographic characteristics, behavior and lifestyle, health status, self-life satisfaction and self-rated health. The subjects were divided into 5 groups according to the sleep time per night:

BackgroundHypertension and diabetes have been included in the list of China's essential public health services since 2009. During these years, the use and associated factors of community health management services in community-living hypertensive and diabetic patients are not very clear and need to be further studied.ObjectiveTo investigate the use and potential associated factors of community health management services in Shenzhen community-living hypertensive and diabetic residents.MethodsData stemmed from the results of Shenzhen Epidemiological Survey on Chronic Non-communicable Diseases and Risk Factors conducted between September and November 2018. The chi-square test and multinomial Logistic regression were used to examine the association of sex, age, place of hukou registration (Shenzhen or not) , marital status, monthly household income per capita, occupation type, years of living in Shenzhen, prevalence of medical insurance enrollment, and the level of medical institutions making a definite diagnosis with the use of community health management services.ResultsAltogether, 10 042 participants were finally enrolled, including 1 132 with self-reported hypertension, and 402 with self-reported diabetes. Among the hypertensive participants, 530 (46.82%) indicated that they received follow-up management of hypertension from the community health center. Specifically, 436 (82.31%) received blood pressure measurement by the doctor, and 399 (75.25%) received medication guidance from the doctor. Of the diabetic patients, 194 (48.26%) indicated that they received follow-up management of diabetes from the community health center. Specifically, 173 (89.37%) of the 193 cases (one case was excluded due to missed information) received blood glucose measurement by the doctor, and 154 (79.62%) received medication guidance from the doctor. The prevalence of hypertensive participants receiving guidance on smoking cessation or smoking less from the doctor was relatively low (lower than 40%) , and so was that of diabetic participants. The prevalence of hypertensive participants receiving guidance on drinking cessation or drinking less from the doctor was relatively low (lower than 40%) , and so was that of diabetic participants. Multinomial Logistic regression analysis revealed that sex, age, monthly household income per capita, years of living in Shenzhen, and prevalence of medical insurance enrollment were associated with the utilization of community health management services in hypertensive patients (P

Myxomycetes are an important component of terrestrial ecosystems, and in order to understand their diversity and phylogenetic relationships, taxonomic issues need to be addressed. In our 1985–2021 biodiversity investigations in Shaanxi Province, Jilin Province, the Inner Mongolia Autonomous Region, Hubei Province, and Henan Province, China, Diderma samples were observed on rotten leaves, rotten branches, and dead wood. The samples were studied, based on morphological features coupled with multigene phylogenetic analyses of nSSU, EF-1α, and COI sequence data, which revealed two new species (Diderma shaanxiense sp. nov. and D. clavatocolumellum sp. nov.) and two known species (D. radiatum and D. globosum). In addition, D. radiatum and D. globosum were newly recorded in Henan Province and the Inner Mongolia Autonomous Region, respectively. The paper includes comprehensive descriptions, detailed micrographs, and the outcomes of phylogenetic analyses for both the newly discovered and known species. Additionally, it offers morpho-logical comparisons between the new species and similar ones. [ABSTRACT FROM AUTHOR]

We used the Rule Space Model, a cognitive diagnostic model, to measure the learning progression for thermochemistry for senior high school students. We extracted five attributes and proposed their hierarchical relationships to model the construct of thermochemistry at four levels using a hypothesized learning progression. For this study, we developed 24 test items addressing the attributes of exothermic and endothermic reactions, chemical bonds and heat quantity change, reaction heat and enthalpy, thermochemical equations, and Hess's law. The test was administered to a sample base of 694 senior high school students taught in 3 schools across 2 cities. Results based on the Rule Space Model analysis indicated that (1) the test items developed by the Rule Space Model were of high psychometric quality for good analysis of difficulties, discriminations, reliabilities, and validities; (2) the Rule Space Model analysis classified the students into seven different attribute mastery patterns; and (3) the initial hypothesized learning progression was modified by the attribute mastery patterns and the learning paths to be more precise and detailed.

Background: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. Methods: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. Results: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35–1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44–2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83–2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. Interpretation: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term. [ABSTRACT FROM AUTHOR]

Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while using prophylactic aspirin for preeclampsia prevention as the best course of treatment. The objective of this study is to investigate the risk factors with the highest risk of developing preeclampsia among pregnant individuals already using aspirin from high-risk obstetrical centers across five countries. This is a secondary analysis of pregnant individuals from the Folic Acid Clinical Trial (FACT) who were using prophylactic aspirin before 16 weeks gestation. The FACT randomized control trial took place in 70 high risk obstetrical centers in Canada, United Kingdom, Australia, Jamaica, and Argentina between 2011–2015. Participants were included if they had any of the risk factors for preeclampsia: diabetes, chronic hypertension, twin pregnancy, history of preeclampsia, and/or obesity (Body Mass Index ≥35). The outcomes of interest were preeclampsia and preterm preeclampsia (<37 weeks). Log binomial regressions assessed factors significantly associated with any preeclampsia or preterm-preeclampsia (<37 weeks) using adjusted risk ratios (ARR) and 95% confidence intervals (CI). There were 2296 pregnant individuals with complete information on aspirin included in this study. At baseline, all patients were at high risk of preeclampsia and were eligible for aspirin prophylaxis, however, only 660 (28.7%) were taking aspirin. Among the 660 pregnant individuals taking aspirin, 132 (20%) developed preeclampsia and 60 (9.09%) preterm preeclampsia. Among pregnant individuals using aspirin, the risks of preeclampsia were highest for twins (ARR:2.62, 95% CI: 1.68–4.11), history of preeclampsia (ARR: 2.42, 95% CI: 1.74–3.38), and hypertension (ARR:1.92, 95% CI: 1.37–2.69). Similar trends were found for preterm-preeclampsia for twins (ARR:4.10, 95% CI:2.15–7.82), history of preeclampsia (ARR:2.75, 95% CI:1.62–4.67), and hypertension (ARR:2.18, 95% CI:1.28–3.72). No significant differences were found for obesity or diabetes. These findings suggest that individuals with twin pregnancies, a history of preeclampsia, or hypertension may not benefit from aspirin to the same extent as those with other complications such as obesity or diabetes. Careful clinical monitoring for these risks factors is recommended and future research into the effectiveness in these populations would increase our understanding of the current best practice of prophylactic aspirin use to prevent preeclampsia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159 [ABSTRACT FROM AUTHOR]

Background: The ubiquitin‐proteasome system (UPS) is a highly conserved way of regulating intracellular protein balance. UPS mediates proteolysis and disruption of variation or misfolding, while finely regulating proteins involved in differentiation and other biological processes. Aims: The aim of this review is to systematically introduce UPS as a key regulator of melanin metabolism. Methods: Systematic search and retrospective review were performed on the published data. Results: Melanocyte‐inducing transcription factor (MITF) is a substrate of the ubiquitin ligase VCHL1 and acts as a transcription factor to regulate the expression of key enzymes in melanin synthesis such as tyrosinase (TYR). The rate‐limiting enzyme TYR is modified by the ubiquitin ligase Hrd1 during melanosynthesis. Melanin itself is also regulated by multiple ubiquitin ligases including Fbp1 and Vhl. By regulating the ubiquitination modification to target each link of melanin synthesis, it plays an important role in correcting the disorder of melanin metabolism. A number of chemical agents have been proven to inhibit the activity of ubiquitin ligase. Conclusions: Drugs targeting E3 ligase and deubiquitinating enzymes have great potential in the treatment of melanin metabolism disorders. [ABSTRACT FROM AUTHOR]

Introduction: Racial differences in adverse maternal and birth outcomes have been studied in other countries, however, there are few studies specific to the Canadian population. In this study, we sought to examine the inequities in adverse perinatal outcomes between Black and White pregnant people in Ontario, Canada. Methods: We conducted a population-based retrospective cohort study that included all Black and White pregnant people who attended prenatal screening and had a singleton birth in any Ontario hospital (April 1st, 2012-March 31st, 2019). Poisson regression with robust error variance models were used to estimate the adjusted relative risks of adverse perinatal outcomes for Black people compared with White people while adjusting for covariates. Results: Among 412,120 eligible pregnant people, 10.1% were Black people and 89.9% were White people. Black people were at an increased risk of gestational diabetes mellitus, preeclampsia, placental abruption, preterm birth (<37, <34, <32 weeks), spontaneous preterm birth, all caesarean sections, emergency caesarean section, low birth weight (<2500g, <1500g), small-for-gestational-age (<10th percentile, <3rd percentile) neonates, 5-minute Apgar score <4 and <7, neonatal intensive care unit admission, and hyperbilirubinemia requiring treatment but had lower risks of elective caesarean section, assisted vaginal delivery, episiotomy, 3rd and 4th degree perineal tears, macrosomia, large-for-gestational-age neonates, and arterial cord pH≤7.1, as compared with White people. No difference in risks of gestational hypertension and placenta previa were observed between Black and White people. Conclusion: There are differences in several adverse perinatal outcomes between Black and White people within the Ontario health care system. Findings might have potential clinical and health policy implications, although more studies are needed to further understand the mechanisms. [ABSTRACT FROM AUTHOR]