The joint associations of high birth weight and not having siblings with metabolic obesity phenotype among school-aged children and adolescents: A National Survey in China.

OBJECTIVE: Birth weight (BW) and sibling's status are two important indicators of early intrauterine environment and subsequent living environment, but no evidence has emerged on their joint associations on metabolic obesity phenotype. To determine the joint associations between BW and single-child status with childhood metabolic obesity phenotype was our purpose. METHODS: A cross-sectional assessment of children and adolescents aged 7-18 years was performed in Chinese seven provinces in 2013. We obtained anthropometric, blood pressure and biochemical measurements, and distributed questionnaires covering demographic, neonatal and lifestyle characteristics. The metabolic obesity phenotype was defined by 2018 consensus-based criteria. Logistic regression and restricted cubic spline models were applied to evaluate the associations of BW and metabolic obesity phenotype, and estimate the multiplicative interactions and the combined associations of BW and single-child status with metabolic obesity phenotype. RESULTS: Of enrolled 12 346 children and adolescents, the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) was 1.96% and 3.03%. There were 8.95% and 4.03% children with high BW or low BW, and 67.55% did not have siblings. High BW was positively associated with MHO (OR = 1.94, 95%CI = 1.28-2.94). Single-child also had increased odds of MHO and MUO (p < 0.05), and it had joint associations with high BW showing 0.85- to 2.58-fold higher odds of MUO and MHO. CONCLUSIONS: High BW and single-child status have joint positive associations with the subsequent odds of MHO and MUO, which should be jointly prevented through earlier screening and subsequent preventive strategies.

Filial piety, love or money? Foundation of old-age support in urban China.

This article explores the intertwining issues of filial obligation, material interest and emotional intimacy in driving adult children's provision of old-age support in family settings. Drawing upon multi-generational life history interviews with urban Chinese families, this article reveals how the configuration of these multiple forces is governed by the socio-economic and demographic context of a particular time. The findings dispute a lineal modernization model of transition and generational change (from past family relations structured by filial obligation to the present emotion-laden nuclear family). Instead the multi-generational analysis reveals a tightening association of multiple forces around the younger generation, intensified by the one-child demographic structure, post-Mao commercialization of urban housing and establishment of the market economy. Finally, this article highlights the role of performance in carrying out old-age support. "Surface work" is enacted in situations where tensions between conformity to public morality and private intents (emotional or material) cannot be reconciled.

LINP1 represses unfolded protein response by directly inhibiting eIF2α phosphorylation to promote cutaneous squamous cell carcinoma.

BACKGROUND: Endoplasmic reticulum stress (ER stress) may destroy endoplasmic reticulum homeostasis (ER homeostasis) and leads to programmable cell death. Unfolded protein response (UPR) originally stimulated by ER stress is critical for the survival of tumor cells through trying to re-establish ER homeostasis as an adaption to harsh microenvironment. However, mechanisms involving key regulators in modulating UPR remain underexplored. METHODS: The expression of LINP1 in cutaneous squamous cell carcinoma (cSCC) tissues and cell lines was assessed. Subsequently, LINP1 was knocked out, knocked down or overexpressed in cSCC cells. CCK-8 assays, colony forming assays, transwell migration assays and invasiveness measurement by matrigel-coated transwell were performed to examine the role of LINP1 in cSCC development through gain-of-function and loss-of-function experiments. Transcriptomic sequencing (RNA-Seq) was conducted and indicated the key downstream signaling events regulated by LINP1 including UPR and apoptosis signaling. Furthermore, the direct interaction between LINP1 and eIF2α to modulate UPR and apoptosis was confirmed by RNA pulldown, RNA immunoprecipitation (RIP), ChIP-qPCR and in vitro phosphorylation assays. RESULTS: In this study, LncRNA in non-homologous end joining pathway 1 (LINP1) was identified to be one of the top ten highest-expressed LncRNAs in cSCC, the second most common cancer in the world. Functional studies using in vitro and in vivo models revealed that LINP1 functions as an oncogene to promote cell proliferation, colony formation, migration and invasiveness while inhibiting cell apoptosis in cSCC. Transcriptomic sequencing after knockdown of LINP1 indicated LINP1 negatively regulates UPR-related pathways involving key effectors for activating UPR and the apoptosis following the prolonged UPR. Mechanistic study showed LINP1 physically interacts with eIF2α to inhibit its phosphorylation for avoiding unmitigated UPR. Loss of LINP1 followed by enhanced eIF2α phosphorylation led to overactivated UPR and induced DDIT3 expression, contributing to ER stress-induced apoptosis and suppression of cSCC development. CONCLUSIONS: Our findings demonstrate a novel regulatory hierarchy of UPR by demonstrating LINP1 as a critical modulator for eIF2α phosphorylation and a suppressor of UPR-mediated apoptosis, which suggests a novel therapeutic target for cSCC treatment.

Refined assessment and decomposition analysis of carbon emissions in high-energy intensive industrial sectors in China.

Carbon emissions from high-energy intensive industrial sectors are the focus of this study due to the huge energy consumption of these sectors. A refined carbon emission inventory of Chinese high-energy intensive industrial sectors in 2020 was first developed at the point source level. The results showed that coal-fired power plants (CFPPs) were the leading contributors to carbon emissions, followed by iron and steel smelting (ISS) and cement production (CMP). Provinces with high carbon emission intensity were mainly concentrated in the north and northeast coasts, while exhibiting a developed economic level and a concentration of heavy industries. Additionally, the growth in China's industrial carbon emissions from 1995 to 2020 can be divided into three phases. The largest decrease in emission intensity was observed in Central, Southwest, North, and East China. Furthermore, the economic structure remained the dominant driver of carbon emissions from the 10th to 13th Five-Year Plan (FYP), playing a positive promotional role. The contribution of economic structure, energy intensity, and energy structure to carbon emissions varied substantially by region and period. With the proposal of sustainable development and energy conservation in China, the influence of economic structure on the carbon emissions of industrial sectors has gradually weakened since the 11th FYP. The reduction in industrial carbon emissions in China under three scenarios could reach up to 46.6 % from 2030 to 2050. The results indicate that industrial carbon emission control in China needs to be integrated into the refined control pathway for conventional air pollutants, considering the spatial variability of industrial carbon emissions in China.

Application of loofah and insects in a bio-trickling filter to relieve clogging.

Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. The BTF was started up within 17 d and restarted within 3 d after starvation for 12-16 d. Its average removal efficiency was >90% at steady state. The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. The introduction of holometabolous insects (Clogmia albipunctata) rapidly removed the biofilm and accelerated the degradation of the loofah, which alleviated clogging. Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. Insect introduction and loofah migration had little effect on the evolution of microflora. This study provides a promising approach to operating BTFs with less clogging.

Distribution, chemical fractionation, and potential environmental risks of Hg, Cr, Cd, Pb, and As in wastes from ultra-low emission coal-fired industrial boilers in China.

This study conducted a comprehensive investigation of the distribution, chemical fractionation, and potential environmental risks of Hg, Cd, Cr, Pb, and As in waste based on new data from five ultra-low emission (ULE) coal-fired industrial boilers (CFIBs). The results showed that fly ash was enriched with Cd, Pb, As, and Hg, while its Cr contents were not invariably higher than those of slag. Fly ash was the predominant output flow for Hg, Cd, Cr, Pb, and As in the tested ULE boilers, with higher proportions of HTEs in the fly ash and lower proportions of HTEs in the flue gas than in the non-ULE boilers. The average proportions of residual Hg, Cd, Cr, Pb, and As in wastes revealed the following order: slag > fly ash > flue gas desulfurization (FGD) by-products. The potential environmental risks of Hg, Cd, Cr, Pb, and As in the fly ash, slag, and FGD by-products of CFIBs at the county level in the Beijing-Tianjin-Hebei Air Pollution Transmission Channel Cities ("2 +26 cities") region showed spatial heterogeneity. It is predicted that the potential release of Pb, Cr, and Cd in the fly ash would increase and that of the FGD by-products would decrease after the implementation of the ULE retrofitting of all CFIBs.

The heteroaggregation behavior of nanoplastics on goethite: Effects of surface functionalization and solution chemistry.

Nanoplastics have attracted extensive attention in recent years. However, little is known about the heteroaggregation behavior of nanoplastics on goethite (FeOOH), especially the contribution of surface functional groups. In this study, the heteroaggregation behavior between polystyrene nanoplastics (PSNPs) and FeOOH was systematically investigated under different reaction conditions. Moreover, the effect of different functional groups (-NH2, -COOH, and bare) of PSNPs and solution chemistry was evaluated. The results showed that PSNPs could heteroaggregate with FeOOH, and the heteroaggregation rate of PSNPs with surface functionalization was significantly faster. The removal of suspended PSNPs was enhanced with increasing NaCl or CaCl2 concentration. However, heteroaggregation was significantly inhibited with the increase of solution pH. The zeta potentials analysis, time-resolved dynamic light scattering (DLS) and heteroaggregation experiments suggested that the electrostatic force affected the heteroaggregation process significantly. Fourier transform infrared (FTIR) spectra proved that the adsorption affinity between PSNPs and FeOOH was stronger after surface functionalization, especially for CH, O-C=O, and -CH2- groups, indicating that chemical bonding also made a contribution during the heteroaggregation process. This work is expected to provide a theoretical basis for predicting the environmental behavior between PSNPs and FeOOH.

Association of fast-food restaurants with overweight and obesity in school-aged children and adolescents: A systematic review and meta-analysis.

We aimed to explore associations between the accessibility of fast-food restaurants (FFRs) and weight-related outcomes in children and adolescents through a systematic review and meta-analysis of studies. We searched three databases for studies published before October 21, 2022. Study quality was assessed using the National Institutes of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Meta-analysis was performed, and the leave-one-out method was used for sensitivity analysis. A total of 60 studies were included. According to our analysis, FFRs within a smaller buffer radius from residences or that provide unhealthy foods may have a more significant influence on children's and adolescents' weight. Children of younger ages and girls may have a higher possibility of being overweight due to FFRs. Though we could hardly avoid bias, the estimates in low-and middle-income countries (only six studies) are much higher than those in high-income countries (54 studies). More research analyses based on microscope data and individual economic levels are needed. This study yields quantitative results, provides policymakers and urban planners with a theoretical support for building resilient and sustainable human settlements, and promotes the translation of research findings from public health to environmental planning.

Analysis and study of the migration pattern of microplastic particles in saturated porous media pavement.

This work aims to establish an analytical and comparative model of pavement stormwater runoff and determine how to solve water pollution in saturated porous media pavements. Heavy metal element particles in the stormwater runoff due to the rainfall will cause inevitable environmental pollution. First, the pavement runoff and materials of saturated porous media are analyzed. Besides, particle migration laws and separation effects of different materials are compared. Based on this, microplastics are selected as the primary material for pavement filling. Then, the adsorption effect of microplastics and the parameters of rainwater infiltration rate and infiltration ratio are analyzed to propose a multi-level ecological integrated treatment system for pavement runoff. Specifically, the environmental resource pollution and saturated porous media materials are analyzed. In addition, the adsorption effect of microplastic particles is analyzed to establish a model to study the selection process of the optimal adsorption material. The main contribution of the research is to analyze the migration process of metal particles in the soil in combination with the internal particle migration rules of plastic granular materials. The research results demonstrate that the rain runoff coefficient gradually increases with the expansion of the permeable area of the pavement. The rain runoff coefficient reaches the maximum value under the pavement of 120 square meters. In addition, a comparative analysis of three street pavements is conducted on the residential street pavement (RSP), commercial street pavement (CSP), and active street pavement (ASP). When comparing the two sets of data, the overall average permeability of the RSP is better than CSP and ASP. The research materials are compared under isothermal conditions. The particle adsorption effect of the same material at 50 °C is significantly better than that at 30 °C. Therefore, it is feasible to resolve the pavement runoff water pollution through technical schemes.

Resveratrol rescues cutaneous radiation-induced DNA damage via a novel AMPK/SIRT7/HMGB1 regulatory axis.

Cutaneous radiation injury (CRI) interrupts the scheduled process of radiotherapy and even compromises the life quality of patients. However, the current clinical options for alleviating CRI are relatively limited. Resveratrol (RSV) has been shown to be a promising protective agent against CRI; yet the mechanisms of RSV enhancing radioresistance were not fully elucidated and limited its clinical application. In this study, we demonstrate RSV promotes cutaneous radioresistance mainly through SIRT7. During ionizing radiation (IR) treatment, RSV indirectly phosphorylates and activates SIRT7 through AMPK, which is critical for maintaining the genome stability of keratinocytes. Immunoprecipitation and mass spectrometry identified HMGB1 to be the key interacting partner of SIRT7 to mediate the radioprotective function of RSV. Mechanistic study elucidated that SIRT7 interacts with and deacetylates HMGB1 to redistribute it into nucleus and "switch on" its function for DNA damage repair. Our findings establish a novel AMPK/SIRT7/HMGB1 regulatory axis that mediates the radioprotective function of RSV to alleviate IR-induced cutaneous DNA injury, providing an efficiently-curative option for patients with CRI during radiotherapy.

The Cumulative Effect of Multilevel Factors on Myopia Prevalence, Incidence, and Progression Among Children and Adolescents in China During the COVID-19 Pandemic.

Purpose: To estimate the effects of school closures and associated lifestyle changes on myopia in Chinese children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Two cross-sectional surveys recruited 14,296 Chinese students aged 7 to 18 years in November 2019 and June 2020 from which an open cohort study (nested queue design) was derived and used to assess myopia prevalence, incidence, and progression rates (defined as students with progression in myopia severity at the second survey wave among those with myopia at baseline). The severity of myopia was determined by measurements of visual acuity (<5.0) and noncycloplegic refraction (spherical equivalent <-0.50 diopters). Twenty-three myopia-influencing factors were divided into three categories: eye-use habits, lifestyle, and family and subjective factors. Responses to each of these 23 factors were labeled as either positive or negative options and then combined to generate a comprehensive score. Results: Boys and girls were equally represented (50%) and had the same average age (11.5 years) at each wave. The myopia prevalence increased from 48.2% to 60.0%, with 27.1% myopia incidence and 13.2% myopia progression rates for Chinese children and adolescents. Each of the 23 factors was associated with myopia prevalence but had no significant effect on myopia incidence or progression. However, these 23 factors had a cumulative effect on myopia risks; higher scores were associated with more positive factors and lower risk ratios of myopia and vice versa. Except for the progression rate, the myopia prevalence and incidence and risk ratios decreased with higher comprehensive scores. Conclusions: School closures during the COVID-19 pandemic increased the risk of myopia in Chinese children and adolescents due to the accumulation of poor eyesight habits, unhealthy lifestyles, and excessive screen time. Translational Relevance: Rather than focusing on single risk factors for myopia, future myopia prevention strategies should focus on integrating multiple comprehensive approaches across schools, families, and communities.

Alternations of vitamin D and cognitive function in first-diagnosed and drug-naïve BD patients: Physical activity as a moderator.

BACKGROUND: The pathophysiological mechanism of cognitive impairments of bipolar disorder (BD) has not yet been completely revealed. It is well known that Vitamin D and physical activity (PA) are associated with BD. However, specific links between Vitamin D and cognitive deficits in BD are still unclear. METHOD: The serum levels of vitamin D were measured. The cognitive performances of 102 first-diagnosed and drug-naïve BD patients were evaluated for analysis. The repeatable battery for the assessment of neuropsychological status (RBANS) and the Stroop Color-Word test was used in this study. PA was collected by international physical activity questionnaire. RESULT: Patients with BD had high levels of serum vitamin D. Furthermore, immediate and delayed memory was negatively associated with vitamin D levels in patients' group. The serum levels of vitamin D in patients with low PA were positively associated with memory. However, increased PA attenuated the protective effect of vitamin D on executive cognition. CONCLUSION: It is concluded that the increased levels of vitamin D were observed in the serum of patients with BD. Thus, it is found that more PA is less beneficial to cognition of patients with BD than longer resting.

Influence of Parental and Offspring Dietary Behaviors on the Association of Overweight and Obesity between Two Generations: Results from a Cross-Sectional Analysis of Parent-Offspring Trios in China.

Limited evidence exists on the influence of dietary behaviors on the association of overweight/obesity between parents and offspring. This study aimed to investigate the influence of dietary behaviors on the association of overweight/obesity between two generations, and puts forward strategies for preventing childhood obesity. Data were obtained from a cross-sectional survey conducted in China; a total of 40,197 parent-offspring pairs were included. Overweight/obesity was defined based on the body mass index and waist circumstance; the association of overweight/obesity between two generations was evaluated by multivariate and binary logistic regression and stratified analyses. Compared with the offspring who were free of parental overweight/obesity, the ORs of offspring with both parental overweight/obesity reached 2.66, 1.72 and 4.04 for general, simple abdominal and compound obesity. The offset effect of dietary behaviors was observed on the association between parental obesity and the offspring's general or simple abdominal obesity, with non-significant ORs when parents or/and offspring had healthy dietary behaviors. It was difficult for a healthy diet alone to offset the high heritability and intergenerational transmission of childhood obesity caused by parental obesity. Multifaceted improvement of lifestyle behaviors, and a combination of individual and family engagement, could be targeted measures to control childhood obesity.

The influence of three-dimensional structure on naïve T cell homeostasis and aging.

A breakdown in cellular homeostasis is thought to drive naïve T cell aging, however the link between naïve T cell homeostasis and aging in humans is poorly understood. To better address this, we developed a lymphoid organoid system that maintains resting naïve T cells for more than 2 weeks, in conjunction with high CD45RA expression. Deep phenotypic characterization of naïve T cells across age identified reduced CD45RA density as a hallmark of aging. A conversion from CD45RAhigh naive cells to a CD45RAlow phenotype was reproduced within our organoid system by structural breakdown, but not by stromal cell aging or reduced lymphocyte density, and mediated by alternative CD45 splicing. Together, these data suggest that external influences within the lymph node microenvironment may cause phenotypic conversion of naïve T cells in older adults.

Exploring the associations between behavioral health risk factors, abnormal eating attitudes and socio-demographic factors among Chinese youth: Survey of 7,984 vocational high school students in Hunan in 2020.

Background: This study investigated the associations between behavioral health risk factors (anxiety, depression, stress, insomnia, drinking, smoking) and abnormal eating attitudes among Chinese vocational high school students (CVHSS). Potential moderating relationships were also explored with relevant socio-demographic factors of the student's age, sex, rural or urban community, household income, family type and educational level of the father and mother. Methods: A total of 7,984 students from three vocational high schools in Hunan, China completed a questionnaire about their socio-demographic characteristics, alcohol use, smoking, and symptoms of depression, anxiety, stress (21-item version of the Depression Anxiety Stress Scale), insomnia (8-item Athens Insomnia Scale), and abnormal eating attitudes (19-item Chinese version of Eating Attitudes Test). Results: The prevalence rates for behavioral health problems among these students ranged widely depending on the risk factor: 42.5% insomnia, 41.3% anxiety, 26.2% depression, 14.4% stress, 13.7% drinking, and 8.3% smoking. Additionally, 61.7% of students were at-risk for at least one of these six behavioral health disorders. Abnormal eating attitudes were associated with depression (r = 0.422), anxiety (r = 0.490), stress (r = 0.490), and insomnia (r = 0.375), with all of these relationships being significant (p < 0.01) and large size statistical effects. However, other analyzes found that none of the socio-demographic background factors had meaningful associations with the behavioral health risk factors (0 of 28 tests) and very few background factors were associated with the abnormal eating attitude measures (only 3 of 35 tests). Females had higher levels than males on dieting and bulimia but not on the other two eating attitude components. Conclusions: This study determined that behavioral health risk factors (sleep problems and anxiety in particular) were common among high school students in China and that mental health and sleep disorder risks also tended to co-occur in some students with abnormal eating attitudes. Therefore, prevention and early identification programs for behavioral risk factors are needed for this population. It is important to pay more attention to students with abnormal eating attitude-related symptoms, who may have also underlying mental health problems and need further evaluation.

Effectiveness of national multicentric school-based health lifestyles intervention among chinese children and adolescents on knowledge, belief, and practice toward obesity at individual, family and schools' levels.

Background: This study aims to evaluate the effectiveness of the trial of national multicentric school-based health lifestyles intervention toward childhood obesity on the KBP at individual, family and schools' levels. Methods: The national trial was a multi-centered, cluster-controlled trial, which was conducted in seven provinces from September 2013 to February 2014, aiming at preventing childhood overweight and obesity. Integrated intervention strategies focused on changing specific practice related to energy intake and expenditure, such as decreasing the consumption of sweetened fizzy drinks, increasing the consumption of vegetables, ensuring proper protein intake, reducing sedentary practice including screen time, and maintaining at least 1 h of moderate to vigorous physical activity. A total of 27,477 children and adolescents in the control group and 30,997 in the intervention group were recruited with a mean follow-up period of 6.7 months. The binomial response mixed-effects model was used for assessing the effects of the national school-based health lifestyles intervention on obesity-related KBP at students individual, parents' and schools' levels. Results: Children and adolescents in the intervention group mastered better obesity-related knowledge, and they had higher correct response rates to all questions about obesity-related knowledge compared to the control group (P < 0.05). In terms of obesity-related belief, individuals in the intervention group was more motivated than the control group, participants in the intervention group had higher correctness of 71.18, 52.94, and 56.60% than the control group of 68.61, 49.86, and 54.43%, (P < 0.05). In addition, healthier habits of eating breakfast and drinking milk every day were observed in the intervention group. For the beliefs toward obesity, parents of the intervention group had higher correctness than the control group. At the same time except for the fruit consumption, other obesity-related practice in the intervention group were healthier than the control group (P < 0.05). Except for some beliefs and practice, the intervention effect at the parent level was not significant in other aspects. Conclusion: The obesity-related knowledge and beliefs of children and adolescents got improved significantly. However, the effects on the knowledge, beliefs and certain practices of their parents and school administrators failed to reach significance.

Prevalence and associated factors of metabolic body size phenotype in children and adolescents: A national cross-sectional analysis in China.

Background: Metabolically healthy obesity (MHO) is a group of subjects with overweight/obesity who present a metabolically healthy profile; however, associated factors are complex and are far from completely understood. The aim of the current study was to estimate the prevalence of different metabolic body size phenotypes and investigate the associated factors in Chinese children and adolescents. Methods: A cross-sectional survey was conducted of 12,346 children and adolescents aged 7-18 years from seven provinces in China in 2013. Anthropometric, blood pressure, and biochemical measurements were obtained. A multi-component questionnaire covering demographic, neonatal, and lifestyle characteristics was administered. The classification of metabolic body size phenotype based on three definitions was compared. With metabolically healthy with normal weight (MHNW) as a reference group, logistic regression analyses were used to estimate the potential effects of associated risk factors, with adjustment for age, sex, single-child status, and residence area. Results: The prevalence of MHNW, MHO, metabolically unhealthy with normal weight (MUNW), and metabolically unhealthy overweight/obesity (MUO) phenotype was 68.6%, 2.0%, 26.4%, and 3.0%, respectively. There were 39.3% MHO and 60.7% MUO among obese participants and 72.2% MHNW and 27.8% MUNW among those with normal weight. Compared to cardiometabolic risk factor (CMRF) criteria and metabolic syndrome (MetS) component definition, the application of the 2018 consensus-based definition may identify more children with abnormal cardiovascular risks, independent of weight status. Compared to younger children, older-aged adolescents were positively associated with higher risks of MUNW (odds ratio (OR) = 1.38, 95% CI = 1.27-1.50) and MUO (OR = 1.29, 95% CI = 1.04-1.60), while factors positively associated with MHO were younger age, single-child status, urban residence, high birth weight, prolonged breastfeeding duration, parental overweight/obesity status, long screen time, and less physical activity. Conclusion: There were still a high proportion of children and adolescents at high cardiometabolic risk in China. Our findings reinforce the need for cardiometabolic risk prevention in children and adolescents irrespective of their weight statuses, such as parental educational programs and healthy lifestyle interventions.

Eucommia ulmoides bark extract reduces blood pressure and inflammation by regulating the gut microbiota and enriching the Parabacteroides strain in high-salt diet and N(omega)-nitro-L-arginine methyl ester induced mice.

Hypertension is a major threat to human health. Eucommia ulmoides Oliv. (EU) is a small tree and EU extract is widely used to improve hypertension in East Asia. However, its major constituents have poor absorption and stay in the gut for a long time. The role of the gut microbiota in the anti-hypertensive effects of EU is unclear. Here, we examined the anti-hypertensive effects of EU in high-salt diet and N(omega)-nitro-L-arginine methyl ester (L-NAME) induced mice. After receiving EU for 6 weeks, the blood pressure was significantly reduced and the kidney injury was improved. Additionally, EU restored the levels of inflammatory cytokines, such as serum interleukin (IL)-6 and IL-17A, and renal IL-17A. The diversity and composition of the gut microbiota were influenced by administration of EU; 40 significantly upregulated and 107 significantly downregulated amplicon sequence variants (ASVs) were identified after administration of EU. ASV403 (Parabacteroides) was selected as a potential anti-hypertensive ASV. Its closest strain XGB65 was isolated. Furthermore, animal studies confirmed that Parabacteroides strain XGB65 exerted anti-hypertensive effects, possibly by reducing levels of inflammatory cytokines, such as renal IL-17A. Our study is the first to report that EU reduces blood pressure by regulating the gut microbiota, and it enriches the Parabacteroides strain, which exerts anti-hypertensive effects. These findings provide directions for developing novel anti-hypertensive treatments by combining probiotics and prebiotics.

Habitual dairy consumption is inversely associated with depressive and social anxiety symptoms among children and adolescents aged 7-17 years: Findings from a cross-sectional study in Beijing, China.

BACKGROUND: Knowledge remains limited about dairy consumption and childhood depression and social anxiety, which is our purpose. METHODS: A cross-sectional study including children and adolescents aged 7-17 years was conducted in 2020 in Beijing. Depression and social anxiety were assessed using the Children's Depression Inventory and the social anxiety scale for children. Habitual dairy consumption was defined as ≥6 days/week. Multivariate linear and logistic regression models were employed to analyze the associations between dairy consumption and depression and social anxiety. Subgroup analyses were conducted to test the robustness of the main results. RESULTS: A total of 1353 participants were included, with a mean age of 12.06 (SD = 3.10) years old. There were 53.58 % habitual dairy consumers and nearly 11.01 % consumed of ≤1 day/week. The prevalence of depression and social anxiety was 14.04 % and 29.64 %. Compared to participants with less dairy intake, the scores of depression and social anxiety in habitual dairy consumers decreased by 1.725 (95 % CI: -2.939, -0.512) and 1.083 (95 % CI: -1.821, -0.345). Correspondingly, habitual dairy consumption was inversely correlated with depression (OR = 0.602, 95%CI: 0.369-0.982) and social anxiety (OR = 0.622, 95%CI: 0.418-0.923). Such inverse associations were more pronounced in younger participants, those without siblings, with higher parental education and higher consumption of fruits or vegetables. LIMITATIONS: Conclusions about causality remain speculative due to the cross-sectional design. CONCLUSIONS: Habitual dairy consumption is inversely associated with childhood depression and social anxiety. A potential attempt could be implemented when recommending dairy products as an adjuvant therapy for childhood mental disorders.

Design, synthesis, and biological evaluation of Wee1 kinase degraders.

Proteolysis targeting chimera (PROTAC) technology has received widespread attention in recent years as a promising strategy for drug development. Herein, we report a series of novel Wee1 degraders, which were designed and synthesized based on PROTAC technology by linking AZD1775 with CRBN ligands through linkers of different lengths and types. All degraders could effectively and completely degrade cellular Wee1 protein in MV-4-11 cell line at IC50 concentrations. Preliminary assessments identified 42a as the most active degrader, which possessed potent antiproliferative activity and induced CRBN- and proteasome-dependent degradation of Wee1. Moreover, 42a also exhibited a time- and concentration-dependent depletion manner and inducing cell cycle arrest in G0/G1 phase and cancer cell apoptosis. More importantly, 42a showed acceptable in vitro and in vivo pharmacokinetic properties and displayed rapid and sustained Wee1 degradation ability in vivo. Taken together, these findings contribute to understanding the development of PROTACs and demonstrate that our Wee1-targeting PROTAC strategy has potential novel applications in cancer therapy.