A Novel Ultrasound-Based Radiomics Model for the Preoperative Prediction of Lymph Node Metastasis in Cervical Cancer.

OBJECTIVE: The purpose of this retrospective study was to establish a combined model based on ultrasound (US)-radiomics and clinical factors to predict preoperative lymph node metastasis (LNM) in cervical cancer (CC) patients non-invasively. METHODS: A total of 131 CC patients who had cervical lesions found by transvaginal sonography (TVS) from the First Affiliated Hospital of Anhui Medical University (Hefei, China) were retrospectively analyzed. The clinical independent predictors were selected using univariate and multivariate logistic regression analysis. US-radiomics features were extracted from US images; after selecting the most significant features by univariate analysis, Spearman's correlation analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm; four machine-learning classification algorithms were used to build the US-radiomics model. Fivefold cross-validation was then used to test the performance of the model and compare the ability of the clinical, US-radiomics and combined models to predict LNM in CC patients. RESULTS: Red blood cell, platelet and squamous cell carcinoma-associated antigen were independent clinical predictors of LNM (+) in CC patients. eXtreme Gradient Boosting performed the best among the four machine-learning classification algorithms. Fivefold cross-validation confirmed that eXtreme Gradient Boosting indeed performs the best, with average area under the curve values in the training and validation sets of 0.897 and 0.898. In the three prediction models, both the US-radiomics model and the combined model showed good predictive efficacy, with average area under the curve values in the training and validation sets of 0.897, 0.898 and 0.912, 0.905, respectively. CONCLUSION: US-radiomics features combined with clinical factors can preoperatively predict LNM in CC patients non-invasively.

Lateral Piezoelectricity of Alzheimer's Aß Aggregates.

Alzheimer's disease (AD) is the most frequent neurodegenerative disorder in the elderly aged over 65. The extracellular accumulation of beta-amyloid (Aß) aggregates in the brain is considered as the major event worsening the AD symptoms, but its underlying reason has remained unclear. Here the piezoelectric characteristics of Aß aggregates are revealed. The vector piezoresponse force microscopy (PFM) analysis results exhibit that Aß fibrils have spiraling piezoelectric domains along the length and a lateral piezoelectric constant of 44.1 pC N-1. Also, the continuous sideband Kelvin probe force microscopy (KPFM) images display that the increment of charge-induced surface potential on a single Aß fibril is allowed to reach above +1700 mV in response to applied forces. These findings shed light on the peculiar mechano-electrical surface properties of pathological Aß fibrils that exceed those of normal body components.

Numerical thermal assessment and theoretical analysis of horizontal-hole interlock composite insulation blocks.

In this paper, the thermal performance of 54 horizontal-hole interlocking composite insulation blocks was numerically analyzed based on the steady-state heat transfer model, the regulations were found, and prediction models for the thermal parameters of the blocks were established based on the parallel network thermal resistance model. The influence of block types and block materials on the thermal performance was studied, and it was found that the thermal performance of H-shaped interlocking insulation blocks was better than that of crossed-shaped ones, and the lower the thermal conductivity of block materials, the better the thermal performance of blocks, among which the reduction of thermal conductivity of concrete materials improved the thermal performance of blocks the most. The simulated values of thermal conductivity of H-shaped interlocking insulation blocks and thermal conductivity under the parallel network thermal resistance model were highly linearly correlated with correlation coefficients as high as 0.998 and 0.999. This finding enables the prediction models of thermal parameters of H-shaped interlocking insulation blocks to be established with high accuracy and provides an effective guide for the energy-saving design of interlocking insulation blocks wall.

Intrauterine arsenic exposure induces glucose metabolism disorders in adult offspring by targeting TET2-mediated DNA hydroxymethylation reprogramming of HNF4α in developing livers, an effect alleviated by ascorbic acid.

Exposure to arsenic during gestation has lasting health-related effects on the developing fetus, including an increase in the risk of metabolic disease later in life. Epigenetics is a potential mechanism involved in this process. Ten-eleven translocation 2 (TET2) has been widely considered as a transferase of 5-hydroxymethylcytosine (5hmC). Here, mice were exposed, via drinking water, to arsenic or arsenic combined with ascorbic acid (AA) during gestation. For adult offspring, intrauterine arsenic exposure exhibited disorders of glucose metabolism, which are associated with DNA hydroxymethylation reprogramming of hepatic nuclear factor 4 alpha (HNF4α). Further molecular structure analysis, by SEC-UV-DAD, SEC-ICP-MS, verified that arsenic binds to the cysteine domain of TET2. Mechanistically, arsenic reduces the stability of TET2 by binding to it, resulting in the decrease of 5hmC levels in Hnf4α and subsequently inhibiting its expression. This leads to the disorders of expression of its downstream key glucose metabolism genes. Supplementation with AA blocked the reduction of TET2 and normalized the 5hmC levels of Hnf4α, thus alleviating the glucose metabolism disorders. Our study provides targets and methods for the prevention of offspring glucose metabolism abnormalities caused by intrauterine arsenic exposure.

Comparative Pathogenesis of Severe Acute Respiratory Syndrome Coronaviruses.

Over the last two decades the world has witnessed the global spread of two genetically related highly pathogenic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, the impact of these outbreaks differed significantly with respect to the hospitalizations and fatalities seen worldwide. While many studies have been performed recently on SARS-CoV-2, a comparative pathogenesis analysis with SARS-CoV may further provide critical insights into the mechanisms of disease that drive coronavirus-induced respiratory disease. In this review, we comprehensively describe clinical and experimental observations related to transmission and pathogenesis of SARS-CoV-2 in comparison with SARS-CoV, focusing on human, animal, and in vitro studies. By deciphering the similarities and disparities of SARS-CoV and SARS-CoV-2, in terms of transmission and pathogenesis mechanisms, we offer insights into the divergent characteristics of these two viruses. This information may also be relevant to assessing potential novel introductions of genetically related highly pathogenic coronaviruses.

Correlation analysis of electronic screen use and myopia among primary and secondary school students in six provinces and cities of China / 中国学校卫生

Objective@#To study the correlation between electronic screen use and myopia among primary and secondary school students in six provinces and cities in China, in order to provide a scientific basis for comprehensive prevention and control of myopia.@*Methods@#From November 2020 to June 2022, a total of 16 557 primary and secondary school students from six provinces and cities in China (Beijing City, Liaoning Province, Zhejiang Province, Henan Province, Shaanxi Province, Chongqing City) were selected by stratified cluster random sampling and probability smampling methods, and a questionnaire prepared by Beijing Center for Disease Control and Prevention was used to investigate their electronic screen use. According to Screening Criteria for Myopia in Children and Adolescents, 0.5% mass concentration of compound topicamide eye drops was used to paralyze the ciliary muscle and undergo slit lamp optometry. Chisquare test was used to compare the differences between groups, and binary Logistic regression was used to analyze the association between electronic screen use and myopia.@*Results@#About 58.3% of primary and secondary school students used electronic screens for more than two hours a day on average, and 63.4% of primary and secondary school students used continuously electronic products for more than 15 minutes at a time for nonstudy purposes. After adjusting for confounding factors, parents unrestricted use of electronic screen time and electronic screen time ≥2 h/d were positively correlated with myopia (OR=1.27, 1.13, P<0.05). Gender stratified analysis showed that boys who used electronic screen time ≥2 h/d had a higher risk of myopia (OR=1.15, P<0.05). The results of grade stratification analysis showed that parents unrestricted electronic screen use time and electronic screen time ≥2 h/d were positively correlated with myopia in the lower grade of primary school students (OR=1.34, 1.18, P<0.05). Among the higher grade of primary school students, continuous use of electronic screens for nonstudy purposes for more than 15 minutes at one time was positively correlated with myopia (OR=1.18, P<0.05). There was a multiplicative interaction between total screen time and one continuous screen time (OR=1.04, P<0.05).@*Conclusions@#Primary and secondary students in six provinces and cities in China reports excessive electronic screen usage which is associated with myopia. Schools and parents should jointly limit the use of electronic screen among primary and secondary students to reduce the occurrence of myopia.

SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models.

SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It is now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters cells via cathepsins, but these findings have yet to be verified in more relevant cell models. Although we could confirm efficient cathepsin-mediated entry for Omicron in a monkey kidney cell line, experiments with protease inhibitors showed that Omicron (BA.1 and XBB1.5) did not use cathepsins for entry into human airway organoids and instead utilized TTSPs. Likewise, CRISPR-edited intestinal organoids showed that entry of Omicron BA.1 relied on the expression of the serine protease TMPRSS2 but not cathepsin L or B. Together, these data force us to rethink the concept that Omicron has adapted to cathepsin-mediated entry and indicate that TTSP inhibitors should not be dismissed as prophylactic or therapeutic antiviral strategy against SARS-CoV-2. IMPORTANCE Coronavirus entry relies on host proteases that activate the viral fusion protein, spike. These proteases determine the viral entry route, tropism, host range, and can be attractive drug targets. Whereas earlier studies using cell lines suggested that the Omicron variant of SARS-CoV-2 has changed its protease usage, from cell surface type II transmembrane serine proteases (TTSPs) to endosomal cathepsins, we report that this is not the case in human airway and intestinal organoid models, suggesting that host TTSP inhibition is still a viable prophylactic or therapeutic antiviral strategy against current SARS-CoV-2 variants and highlighting the importance of relevant human in vitro cell models.

As3MT via consuming SAM is involved in arsenic-induced nonalcoholic fatty liver disease by blocking m6A-mediated miR-142-5p maturation.

Arsenic, a common environmental hazard, is a risk factor for nonalcoholic fatty liver disease (NAFLD). However, the mechanism remains unclear. Here, we found that chronic exposure to environmental-related doses of arsenic disturbed fatty acid and methionine metabolism in mice, caused liver steatosis, increased arsenic (3) methyltransferase (As3MT), sterol regulatory element binding protein 1 (SREBP1) and lipogenic gene levels, and decreased N6-methyladenosine (m6A) and S-adenosylmethionine (SAM) levels. Mechanistically, arsenic blocks m6A-mediated miR-142-5p maturation by consuming SAM via As3MT. miR-142-5p was involved in arsenic-induced cellular lipid accumulation by targeting SREBP1. SAM supplementation or As3MT deficiency blocked arsenic-induced lipid accumulation by promoting the maturation of miR-142-5p. Moreover, in mice, folic acid (FA) and vitamin B12 (VB12) supplementation blocked arsenic-induced lipid accumulation by restoring SAM levels. Arsenic-exposed heterozygous As3MT mice showed low liver lipid accumulation. Our study demonstrates that SAM consumption caused by arsenic, through As3MT, blocks m6A-mediated miR-142-5p maturation, thereby elevating the levels of SREBP1 and lipogenic genes, leading to NAFLD, which provides a new mechanism and biological insights into the therapy of NAFLD induced by environmental factors.

Vascular ring: prenatal diagnosis and prognostic management based on sequential cross-sectional scanning by ultrasound.

BACKGROUND: In terms of embryonic origin, vascular ring is a congenital anomaly in which the aortic arch and its branches completely or incompletely encircle and compress the trachea or esophagus. Early and accurate diagnosis of a vascular ring is the key to treatment. Prenatal diagnosis mainly relies on fetal echocardiography, but the rate of missed diagnosis and misdiagnosis is still very high, and the prognosis has not been evaluated. The aim of this study was to investigate the accuracy of prenatal diagnosis and to evaluate the prognosis semi-quantitatively according to the shape of the ring and the distance between the vessel and the trachea. METHODS: From 2019 to 2021, 37,875 fetuses underwent prenatal ultrasound examination in our center. All fetal cardiac examinations were performed using the fetal echocardiography method proposed by the American Institute of Ultrasound in Medicine (AIUM) combined with dynamic sequential cross-sectional observation (SCS). For SCS, the standard abdominal section was taken as the initial section, and the probe was moved cephalically along the long axis of the body until the superior mediastinum had disappeared. If a vascular ring was found, the shape of the ring and the distance of the branch to the airway were observed. The distance relationship with the airway was divided into three grades: I-III; the closer the distance, the lower the grade. The vascular rings were monitored every 4 weeks before birth. All were monitored before surgery or 1 year after birth. RESULTS: A total of 418 cases of vascular rings were detected. There was no missed diagnoses or misdiagnoses by SCS. The vessels formed different shaped rings according to their origin and route. Grade I, "" and "O" rings have a poor prognosis and are associated with the highest risk of respiratory symptoms. CONCLUSIONS: SCS can accurately diagnose vascular rings before delivery, evaluate the shape and size of the rings to conduct prenatal monitoring of children until birth, which plays a guiding role in airway compression after birth.

Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles.

Infection by many (+)RNA viruses is accompanied by ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus-triggered lipophagy was critical for flaviviral assembly, and is driven by the lipid droplet associated protein Ancient ubiquitin protein 1 (Aup1). A ubiquitin conjugating protein Ube2g2 that functions as a co-factor for Aup1 was identified as a host dependency factor in our study. Here we characterized its function: Ube2g2-deficient cells displayed a dramatic reduction in virus production, which could be rescued by reconstituting the wild-type but not the catalytically deficient (C89K) mutant of Ube2g2, suggesting that its enzymatic activity is necessary. Ube2g2 deficiency did not affect entry of virus particles but resulted in a profound loss in formation of replication organelles, and production of infectious progenies. This phenomenon resulted from its dual activity in (i) triggering lipophagy in conjunction with Aup1, and (ii) degradation of ER chaperones such as Herpud1, SEL1L, Hrd1, along with Sec62 to restrict ER-phagy upon Xbp1-IRE1 triggered ER expansion. Our results therefore underscore an exquisite fine-tuning of selective autophagy by flaviviruses that drive host membrane reorganization during infection to enable biogenesis of viral replication organelles.

Problematic use of social media: The influence of social environmental forces and the mediating role of copresence.

People's dependence on technology in the digital environment has increasingly become the focus of academic and social attention. Social media, in particular, with the functions of connecting with others and maintaining interactions, has become an inseparable part of people's lives. Although the formation of problematic use of social media has been extensively discussed by scholars, it is mainly confined to the individual level and lacks a macro perspective from the external environment. This study draws on the perspective of institutional theory and introduces copresence as a mediating role, aiming to investigate the influence mechanism of social environmental forces on individuals' problematic use of social media. An online survey (N = 462) was conducted to collect data and test the research model. Our data were analyzed using the structural equation modeling (SEM) approach. Results show that social environmental forces exert an impact on problematic use of social media through the sense of copresence, and only mimetic force can directly affect behavior outcomes while the other two forces can not. Besides, social environmental forces have a relationship with people's sense of copresence while using social media. Among them, mimetic force and normative force positively correlate with copresence while coercive force is negatively related to copresence. Furthermore, copresence is found to influence problematic use of social media positively. Practical and theoretical implications are discussed.

Artificial Light-at-Night Exposure and Overweight and Obesity across GDP Levels among Chinese Children and Adolescents.

BACKGROUND: Evidence in adults suggests that exposure to artificial light-at-night (ALAN) leads to obesity. However, little is known about whether this effect exists in children and adolescents. We aimed to investigate whether ALAN exposure was associated with overweight and obesity in school-aged children and adolescents and whether this association varied with socioeconomic status. METHODS: Data on the height and weight of 129,500 children and adolescents aged 10-18 years from 72 cities were extracted from the 2014 Chinese National Survey on Students' Constitution and Health (CNSSCH). The ALAN area percentage and average ALAN intensity were calculated using the Visible/Infrared Imager/Radiometer Suite. The subjects were separated into three categories based on the cities' gross domestic product per capita (GDPPC). A mixed-effect logistic regression model and generalized additive model (GAM) were utilized to evaluate the association between ALAN exposure and overweight and obesity in children and adolescents stratified by municipal GDPPC. RESULTS: Both ALAN area (OR = 1.194, 95% CI: 1.175-1.212) and ALAN intensity (OR = 1.019, 95% CI: 1.017-1.020) were positively associated with overweight and obesity in children and adolescents, and the associations remained robust after adjusting for covariates. ORs for overweight and obesity and ALAN area decreased as GDPPC level increased (first tertile: OR = 1.457, 95% CI: 1.335-1.590; second tertile: OR = 1.350, 95% CI: 1.245-1.464; third tertile: OR = 1.100, 95% CI: 1.081-1.119). Similar results were observed for ALAN intensity. In the GAM models, thresholds existed in almost all these spline trends, indicating that ALAN might have a nonlinear association with overweight and obesity. CONCLUSIONS: ALAN contributed to the development of overweight and obesity in children and adolescents and this effect differed with GDPPC. Future longitudinal studies should confirm the causal relationship between ALAN and obesity. Moreover, reducing unnecessary exposure to artificial light at night may have beneficial implications for controlling childhood and adolescent obesity, particularly in low-income areas.

SIRT1/PGC-1α is involved in arsenic-induced male reproductive damage through mitochondrial dysfunction, which is blocked by the antioxidative effect of zinc.

Exposure to arsenic poses threats to male reproductive system, including impairing the testes and sperm quality. Although an association regarding arsenic exposure and male reproductive damage has been reported, the undergoing molecular mechanisms and interventions for prevention remain unclear. For the present work, male mice were exposed to 0, 2.5, 5, or 10 ppm sodium arsenite (NaAsO2) for 8 months. The results showed that arsenic-exposed mice had reduced fertility with abnormalities in the testes, epididymides, and sperm. Exposure of mice to arsenic caused a redox imbalance, decreased SIRT1 and PGC-1α levels, and affected mitochondrial biogenesis and proteins related to mitochondrial dynamics. For immortalized spermatogenic (GC-2) cells, arsenic caused apoptosis and oxidative stress, reduced SIRT1/PGC-1α levels and ATP production, inhibited mitochondrial respiration, and changed the mitochondrial membrane potential (MMP). Mitochondrial biogenesis and dynamics were also impaired. However, by reducing mitochondrial damage in GC-2 cells, upregulation of SIRT1 or zinc (Zn) supplementation reversed the apoptosis induced by arsenic. For mice, Zn supplementation blocked arsenic-induced oxidative stress, the decreases of SIRT1 and PGC-1α levels, and the impairment of mitochondrial function, and it reversed the damage to testes, low sperm quality, and low litter size. Collectively, these results suggest that arsenic causes excessive production of ROS, inhibits the SIRT1/PGC-1α pathway, and causing mitochondrial dysfunction by mediating impairment of mitochondrial biogenesis and dynamics, which results in germ cells apoptosis and male reproductive damage, processes that are blocked by Zn via an antioxidative effect. Our study contributes to understanding of the mechanisms for arsenic-induced male reproductive damage and points to the therapeutic significance of Zn.

Prevalence of myopia of primary and middle school students in Beijing from 2018 to 2021 / 中国学校卫生

Objective@#To understand the vision status of primary and secondary school students in Beijing, in order to provide scientific reference for myopia prevention and control.@*Methods@#From 2018 to 2021, a stratified cluster sampling method was used to monitor myopia among 191 293 primary and secondary school students selected from 6 urban areas and 10 suburban areas in Beijing. Myopic screening was in accordance with the "standards for children and adolescents myopic screening", and was measured by an automatic desktop computer optometer under non-cycloplegic conditions. Statistical analysis was used by Chi-square test.@*Results@#The total myopia rate of primary and middle school students in Beijing from 2018 to 2021 were 60.7%, 57.6%, 59.2% and 59.7%, respectively. In 2018, the myopia rates of primary school students, middle school students, regular high school students and vocational high school students were 38.3%, 77.3%, 88.3% and 73.2% respectively. In 2019, they were 34.7%, 76.4%, 87.7% and 72.0%, respectively; in 2020, they were 37.5%, 76.8%, 86.8%, 74.9%; in 2021, they were 38.7%, 77.4%, 86.5% and 74.9 % respectively. Significant differences in educational stage were observed ( χ 2=7 386.07, 11 104.28, 9 850.08, 9 714.59, P <0.01). From 2018 to 2021, the overall myopia rate of girls (62.1%) was higher than that of boys (56.5%)( χ 2=613.75, P <0.01). The myopia rate of girls were higher than that of boys in each year, and significant differences in educational stage were observed, respectively( χ 2=120.47, 163.47, 168.01, 162.24, P <0.01). The overall myopia rate of urban students(63.0%) was higher than that of suburban students (56.0%)( χ 2=978.82, P <0.01). The myopia rate of urban students were higher than that of suburban students every year, and significant differences in educational stage were observed, respectively ( χ 2=86.71, 240.96, 302.56, 409.30 , P < 0.01 ).@*Conclusion@#The detection rate of myopia rate of primary and middle school students in Beijing is still high. It is necessary to strengthen the publicity and intervention of poor visual acuity in primary and middle school students, especially among urban area students, with the aim of effectively control and reduction in the myopia rate, and the improvement of student visual health.

A multilevel model analysis of the association between reading and writing posture with myopia in primary and secondary school students / 中国学校卫生

Objective@#To explore the association between reading and writing posture with the occurrence of myopia in Chinese children and adolescents, so as to provide a reference for reducing its prevalence among primary and secondary school students.@*Methods@#Using data from the 2020 survey on the current status of hyperopia reserve in primary and secondary school students from six provinces/cities, namely Beijing, Zhejiang, Chongqing, Shaanxi, Liaoning, and Henan selected by multi stage stratified cluster probability sampling method during November 2020 to June 2022. A total 16 782 students who completed the optometry examination of cycloplegia according to the Children and Adolescents Myopia Screening Standard and questionnaire survey were included for analyzing analyze the association between reading and writing posture with myopia.@*Results@#The overall detection rate of myopia among primary and secondary school students was 45.7%, of which 35.0% were primary school students, 84.1% junior high school students, and 90.4% senior high school students. Poor reading and writing posture was found in 73.6% of primary and secondary school students. Adjusting for confounding factors such as gender, school period, region, outdoor time every day, and whether parents were myopic, the results of the multilevel Logistic regression showed that the following factors were positively correlated with myopia:poor reading and writing posture ( OR=1.17, 95%CI =1.07-1.28), never/occasionally reading and writing with a reading distance which was more than one foot away between the eyes and book ( OR=1.28, 95%CI=1.08-1.53, OR=1.23, 95%CI = 1.08- 1.40), teachers occasionally reminding the child of their reading and writing posture ( OR=1.13, 95%CI =1.01-1.25), and often/always reading and writing while lying down or with the face on the arm ( OR=1.15, 95%CI=1.01-1.32, OR=1.46, 95% CI = 1.17-1.82), always reading and writing with the head in the hand ( OR=1.56, 95%CI =1.20-2.01). Further, a negative correlation was detected between myopia and parents occasionally reminding their children of their reading and writing posture ( OR= 0.85 , 95%CI =0.76-0.96) ( P <0.05).@*Conclusion@#Poor reading and writing posture is a risk factor for the development of myopia in primary and secondary school students, and interventions for reading and writing posture need to be strengthened to reduce the occurrence of myopia among primary and secondary school students.

Selenium and vitamin B6 cosupplementation improves dyslipidemia and fatty liver syndrome by SIRT1/SREBP-1c pathway in hyperlipidemic Sprague-Dawley rats induced by high-fat diet.

Previously, our group found that the dietary trace mineral element selenium and vitamin B6 (VitB6) alone was involved in lipid metabolism. However, the effects of selenium combined with VitB6 on hyperlipidemia and lipid metabolism have not been reported until now. We hypothesized that selenium and VitB6 cosupplementation would alleviate the hyperlipidemic and hepatic dysfunction and with minimum side effects in a Sprague-Dawley rat model of hyperlipidemia induced by a high-fat diet. Our results showed that selenium combined with VitB6 could improve dyslipidemia and displayed better in vivo hypocholesterolemic abilities at early intervention. Moreover, cosupplementation reduced atherogenic indexes (atherogenic index and atherogenic index of plasm) and the ratio of ApoB/ApoA1. The liver function index aspartate aminotransferase in serum was reduced, as was and total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol in liver. The intervention also increased the levels of ApoA1 in serum and high-density lipoprotein cholesterol of liver. In addition, the combination of selenium and VitB6 decreased liver lipid deposition and alleviated steatosis, reduced adipocyte size of white adipose tissue, increased the activities of hepatic lipase and total lipase and the hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) level, decreased the hepatic mRNA transcription of lipogenic and regulatory genes including Srebf1 and downstream fat synthesis-related enzymes (Acc and Fasn) and cholesterol synthesis speed limiting enzyme Hmgr, increased the mRNA abundance of Lcat and Cyp7a1, increased the protein expression of SIRT1 and PPARα, and up-regulated the protein expression of sterol regulatory element-binding protein 1c in the livers of hyperlipidemia rats. We first demonstrated that oral selenium and VitB6 cosupplementation exerted synergism in lowering blood and liver lipid profiles and antiatherosclerotic effects in hyperlipidemic rats by reducing endogenous cholesterol and lipid synthesis, enhancing the transport of cholesterol to hepatocytes and promoting fatty acid beta oxidation.

Global trends and regional differences in non-transport unintentional injuries mortality among children and adolescents, 1990 to 2019: results from the Global Burden of Disease 2019 study.

BACKGROUND: Non-transport unintentional injuries (NTUIs) are major public concerns, especially among children and adolescents in low- and middle-income countries. With environmental and cognitive changes, a recent systematic description of global trends and regional differences concerning NTUIs is urgently needed for the global agenda of relevant policy-making and intervention target findings. METHODS: We used mortality, population, and socio-demographic-index (SDI) data from Global Burden of Disease 2019 to analyze the trends of NTUIs mortality. We applied the slope index of inequality (SII) and relative index of inequality (RII) to measure the absolute and relative inequality between countries and territories. The concentration curve and concentration index (CI) were also used to measure the inequality. We conducted a sensitivity analysis to make our findings credible. RESULTS: In 2019, there were 205,000 deaths due to NTUIs among children and adolescents aged 5 to 24 years, which decreased from 375,000 in 1990. In 2019, the age-standardized mortality rate (ASMR) was 8.13 per 100,000, ranging from the lowest in the Netherlands (0.90 per 100,000) to the highest in the Solomon Islands (29.34 per 100,000). The low-middle SDI group had the highest ASMR of NTUIs, while the low SDI group had the slowest decrease. After excluding the death caused by "exposure to forces of nature" and "other unintentional injuries", drowning accounted for the most deaths in almost every SDI group, gender, and age group, but the major causes of death varied in different subgroups. For example, animal contact was a major cause in low and low-middle SDI groups but less in high SDI groups, while high and high-middle SDI groups had a higher proportion of deaths for foreign body and poisonings. The SII showed a declining trend, but the RII and CI did not, which might indicate that inequality was persistent. Similar results were found in the sensitivity analysis. CONCLUSIONS: Despite the declining trend of the mortality rate and the narrowing gap between countries, there were still a large number of children and adolescents dying from NTUIs, and those experiencing social-economic disadvantages remained at high mortality. Embedding the prevention of NTUIs into sustainable development goals might contribute to the progress of reducing death and inequalities, which ensures that no one is left behind.

As3MT-mediated SAM consumption, which inhibits the methylation of histones and LINE1, is involved in arsenic-induced male reproductive damage.

Studies have demonstrated that arsenic (As) induces male reproductive injury, however, the mechanism remains unknown. The high levels of arsenic (3) methyltransferase (As3MT) promote As-induced male reproductive toxicity. For As-exposed mice, the germ cells in seminiferous tubules and sperm quality were reduced. Exposure to As caused lower S-adenosylmethionine (SAM) and 5-methylcytosine (5 mC) levels, histone and DNA hypomethylation, upregulation of long interspersed element class 1 (LINE1, or L1), defective repair of double-strand breaks (DSBs), and the arrest of meiosis, resulting in apoptosis of germ cells and lower litter size. For GC-2spd (GC-2) cells, As induced apoptosis, which was prevented by adding SAM or by reducing the expression of As3MT. The levels of LINE1, affected by SAM content, were involved in As-induced apoptosis. Furthermore, folic acid (FA) and vitamin B12 (VB12) supplements restored SAM, 5 mC, and LINE1 levels and blocked impairment of spermatogenesis and testes and lower litter size. Exposed to As, mice with As3MT knockdown showed less impairment of spermatogenesis and testes and greater litter size compared to As-exposed wild-type (WT) mice. Thus, the high As3MT levels induced by As consume SAM and block histone and LINE1 DNA methylation, elevating LINE1 expression and evoking impairment of spermatogenesis, which causes male reproductive damage. Overall, we have found a mechanism for As-induced male reproductive damage, which provides biological insights into the alleviation of reproductive injury induced by environmental factors.

Epicoccanes A-D, Four Oxidative Dimers of Pyrogallol Analogues from Epicoccum nigrum.

Epicoccanes A-D (1-4) are four novel metabolites of an endophytic fungus Epicoccum nigrum. Their distinct unprecedented structures are hypothesized as oxidative dimers of pyrogallol analogues. Compounds 1 and 2 possess a novel spirobicyclo[3.2.1]octane-6,1'-cyclopentane or -cyclohexane core skeleton. Compound 3 is of a unique cage-like pentacyclic system, which unusually contained three continuous spiro-carbons. Compound 4 is a highly rearranged dimer with five contiguous chiral centers. The absolute structures of 1 and 2 were deduced by electronic circular dichroism (ECD) calculations, and those of 3 and 4 were determined by X-ray crystallography. Compounds 1 and 4 showed potential antiliver fibrosis activity.

Association between household incense burning and executive function in Chinese children.

Incense burning is common in Asia including China. Research investigating the association between household incense burning and children's neurodevelopment is scarce. We aimed to examine this association in Chinese children. In 2019, we randomly enrolled 8293 children aged 6-12 years from 5 elementary schools in Guangzhou, southern China. Information on duration and frequency of household incense burning was collected using a questionnaire. Children's executive function was evaluated using the parental report of the Behavioral Rating Inventory of Executive Function. A general linear model was used to assess the associations between incense burning and executive function. Children who occasionally and frequently exposed to incense burning exhibited worse performance on executive function. For example, frequent incense burning was associated with increases in behavioral regulation index (BRI) of 1.77 (95%CI: 0.97, 2.58) points and metacognition index (MI) of 1.40 (95%CI: 0.60, 2.20) points, compared to never incense burning group. Parental smoking and household income were significant modifiers of the associations, with the stronger associations were observed in children having smoking parent(s) and poorer household income. The findings suggest that household incense burning was associated with poorer executive function, especially in children whose parent(s) were smokers and in those with low household income.