Long-term variations of urban-Rural disparities in infectious disease burden of over 8.44 million children, adolescents, and youth in China from 2013 to 2021: An observational study.

BACKGROUND: An accelerated epidemiological transition, spurred by economic development and urbanization, has led to a rapid transformation of the disease spectrum. However, this transition has resulted in a divergent change in the burden of infectious diseases between urban and rural areas. The objective of our study was to evaluate the long-term urban-rural disparities in infectious diseases among children, adolescents, and youths in China, while also examining the specific diseases driving these disparities. METHODS AND FINDINGS: This observational study examined data on 43 notifiable infectious diseases from 8,442,956 cases from individuals aged 4 to 24 years, with 4,487,043 cases in urban areas and 3,955,913 in rural areas. The data from 2013 to 2021 were obtained from China's Notifiable Infectious Disease Surveillance System. The 43 infectious diseases were categorized into 7 categories: vaccine-preventable, bacterial, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. The calculation of infectious disease incidence was stratified by urban and rural areas. We used the index of incidence rate ratio (IRR), calculated by dividing the urban incidence rate by the rural incidence rate for each disease category, to assess the urban-rural disparity. During the nine-year study period, most notifiable infectious diseases in both urban and rural areas exhibited either a decreased or stable pattern. However, a significant and progressively widening urban-rural disparity in notifiable infectious diseases was observed. Children, adolescents, and youths in urban areas experienced a higher average yearly incidence compared to their rural counterparts, with rates of 439 per 100,000 compared to 211 per 100,000, respectively (IRR: 2.078, 95% CI [2.075, 2.081]; p < 0.001). From 2013 to 2021, this disparity was primarily driven by higher incidences of pertussis (IRR: 1.782, 95% CI [1.705, 1.862]; p < 0.001) and seasonal influenza (IRR: 3.213, 95% CI [3.205, 3.220]; p < 0.001) among vaccine-preventable diseases, tuberculosis (IRR: 1.011, 95% CI [1.006, 1.015]; p < 0.001), and scarlet fever (IRR: 2.942, 95% CI [2.918, 2.966]; p < 0.001) among bacterial diseases, infectious diarrhea (IRR: 1.932, 95% CI [1.924, 1.939]; p < 0.001), and hand, foot, and mouth disease (IRR: 2.501, 95% CI [2.491, 2.510]; p < 0.001) among gastrointestinal and enterovirus diseases, dengue (IRR: 11.952, 95% CI [11.313, 12.628]; p < 0.001) among vectorborne diseases, and 4 sexually transmitted and bloodborne diseases (syphilis: IRR 1.743, 95% CI [1.731, 1.755], p < 0.001; gonorrhea: IRR 2.658, 95% CI [2.635, 2.682], p < 0.001; HIV/AIDS: IRR 2.269, 95% CI [2.239, 2.299], p < 0.001; hepatitis C: IRR 1.540, 95% CI [1.506, 1.575], p < 0.001), but was partially offset by lower incidences of most zoonotic and quarantinable diseases in urban areas (for example, brucellosis among zoonotic: IRR 0.516, 95% CI [0.498, 0.534], p < 0.001; hemorrhagic fever among quarantinable: IRR 0.930, 95% CI [0.881, 0.981], p = 0.008). Additionally, the overall urban-rural disparity was particularly pronounced in the middle (IRR: 1.704, 95% CI [1.699, 1.708]; p < 0.001) and northeastern regions (IRR: 1.713, 95% CI [1.700, 1.726]; p < 0.001) of China. A primary limitation of our study is that the incidence was calculated based on annual average population data without accounting for population mobility. CONCLUSIONS: A significant urban-rural disparity in notifiable infectious diseases among children, adolescents, and youths was evident from our study. The burden in urban areas exceeded that in rural areas by more than 2-fold, and this gap appears to be widening, particularly influenced by tuberculosis, scarlet fever, infectious diarrhea, and typhus. These findings underscore the urgent need for interventions to mitigate infectious diseases and address the growing urban-rural disparity.

Endophytic Fungal Diversity of Mangrove Ferns Acrostichum speciosum and A. aureum in China.

Microbial communities are an important component of mangrove ecosystems. In order to reveal the diversity of endophytic fungi in the mangrove ferns Acrostichum speciosum and A. aureum in China, the internal transcribed spacer (ITS) regions of endophytic fungi in four plant tissues (leaves, petioles, roots, and rhizomes) from three locations (Zhanjiang, Haikou, and Wenchang) were sequenced. The richness, species composition, and community similarity were analyzed. The main results are as follows: the dominant fungi in A. speciosum and A. aureum belonged to the phyla Ascomycota and Basidiomycota, accounting for more than 75% of the total identified fungi; in terms of species composition at the operational taxonomic unit (OTU) level, the endophytic fungi in A. aureum were more diverse than those in A. speciosum, and the endophytic fungi in rhizomes were more diverse than in other tissues. In Zhanjiang, both A. speciosum and A. aureum showed the richest diversity of endophytic fungi, both at the OTU classification level and in terms of species composition. Conversely, the richness of endophytic fungi in the samples of A. speciosum from Wenchang and Haikou is extremely low. The regional differences in dominant fungi increase with the degrading of taxonomic levels, and there were also significant differences in the number of unique fungi among different origins, with Zhanjiang samples having a larger number of unique fungi than the other locations. There were significant differences in the dominant fungi among different tissues, with Xylariales being the dominant fungi in rhizomes of A. speciosum and Hypocreales being the dominant fungi in the petioles, roots, and rhizomes of A. aureum. Overall, the community similarity of endophytic fungi among locations is moderately dissimilar (26-50%), while the similarity between tissues is moderately similar (51-75%). The low diversity of endophytic fungi could be one of the main reasons for the endangerment of A. speciosum. The protection of the diversity of endophytic fungi in the underground parts of A. speciosum is essential for the conservation of this critically endangered mangrove fern.

Discovery of Pyrido[2,3-d]pyrimidin-7-one Derivatives as Highly Potent and Efficacious Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Inhibitors for Cancer Treatment.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an extracellular enzyme responsible for hydrolyzing cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), the endogenous agonist for the stimulator of interferon genes (STING) pathway. Inhibition of ENPP1 can trigger STING and promote antitumor immunity, offering an attractive therapeutic target for cancer immunotherapy. Despite progress in the discovery of ENPP1 inhibitors, the diversity in chemical structures and the efficacy of the agents are far from desirable, emphasizing the demand for novel inhibitors. Herein, we describe the design, synthesis, and biological evaluation of a series of ENPP1 inhibitors based on the pyrido[2,3-d]pyrimidin-7-one scaffold. Optimization efforts led to compound 31 with significant potency in both ENPP1 inhibition and STING pathway stimulation in vitro. Notably, 31 demonstrated in vivo efficacy in a syngeneic 4T1 mouse triple negative breast cancer model. These findings provide a promising lead compound with a novel scaffold for further drug development in cancer immunotherapy.

Effects of continuous low-speed biogas agitation on anaerobic digestion of high-solids pig manure: Performance and microbial community.

This study aimed to investigate effects of continuous low-speed biogas agitation on the anaerobic digestion (AD) performance and microbial community of high-solids pig manure (total solids content of 10%). Our results reveal that at a biogas agitation intensity of 1.10 L/g feed VS/d, CH4 production increased by 16.67% compared to the non-agitated condition, the removal efficiency of H2S reached 63.18%, and the abundance of Methanosarcina was the highest. The presence of Hungateiclostridiaceae was associated with H2S concentrations. An increasing biogas agitation intensity led to an elevated pH and a decreased oxidation-reduction potential (ORP). Acetate concentrations, pH, and ORP values indicated changes in H2S concentrations. Sedimentibacter demonstrates the potential to indicate biogas agitation intensity and pH. We demonstrate that continuous low-speed biogas agitation effectively increases CH4 production and reduces H2S concentrations in AD of high-solids pig manure, offering a potential technical pathway for developing AD processes for high-solids pig manure, it also demonstrates that AD process can reduce the risk of pathogen and parasite transmission.

A novel fully human anti-NT-ANGPTL3 antibody from phage display library exhibits potent ApoB, TG, and LDL-C lowering activities in hyperlipidemia mice.

Dyslipidemia is characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and TG-rich lipoprotein (TGRLs) in circulation, and is closely associated with the incidence and development of cardiovascular disease. Angiopoietin-like protein 3 (ANGPTL3) deficiency has been identified as a cause of familial combined hypolipidemia in humans, which allows it to be an important therapeutic target for reducing plasma lipids. Here, we report the discovery and characterization of a novel fully human antibody F1519-D95aA against N-terminal ANGPTL3 (NT-ANGPTL3), which potently inhibits NT-ANGPTL3 with a KD as low as 9.21 nM. In hyperlipidemic mice, F1519-D95aA shows higher apolipoprotein B (ApoB) and TG-lowering, and similar LDL-C reducing activity as compared to positive control Evinacumab (56.50% vs 26.01% decrease in serum ApoB levels, 30.84% vs 25.28% decrease in serum TG levels, 23.32% vs 22.52% decrease in serum LDLC levels, relative to vehicle group). Molecular docking and binding energy calculations reveal that the F1519-D95aA-ANGPTL3 complex (10 hydrogen bonds, -65.51 kcal/mol) is more stable than the Evinacumab-ANGPTL3 complex (4 hydrogen bonds, -63.76 kcal/mol). Importantly, F1519-D95aA binds to ANGPTL3 with different residues in ANGPTL3 from Evinacumab, suggesting that F1519-D95aA may be useful for the treatment of patients resistant to Evinacumab. In conclusion, F1519-D95aA is a novel fully human anti-NT-ANGPTL3 antibody with potent plasma ApoB, TG, and LDL-C lowering activities, which can potentially serve as a therapeutic agent for hyperlipidemia and relevant cardiovascular diseases.

Second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP): the cell autonomous and non-autonomous roles in cancer progression.

Cytosolic double-stranded DNA (dsDNA) is frequently accumulated in cancer cells due to chromosomal instability or exogenous stimulation. Cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, which is activated upon binding to dsDNA to synthesize the crucial second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP) that in turn triggers stimulator of interferon genes (STING) signaling. The canonical role of cGAS-cGAMP-STING pathway is essential for innate immunity and viral defense. Recent emerging evidence indicates that 2'3'-cGAMP plays an important role in cancer progression via cell autonomous and non-autonomous mechanisms. Beyond its role as an intracellular messenger to activate STING signaling in tumor cells, 2'3'-cGAMP also serves as an immunotransmitter produced by cancer cells to modulate the functions of non-tumor cells especially immune cells in the tumor microenvironment by activating STING signaling. In this review, we summarize the synthesis, transmission, and degradation of 2'3'-cGAMP as well as the dual functions of 2'3'-cGAMP in a STING-dependent manner. Additionally, we discuss the potential therapeutic strategies that harness the cGAMP-mediated antitumor response for cancer therapy.

Associations of school physical activity environment with comorbid obesity and myopia in children and adolescents: Findings from a Chinese national follow-up study.

BACKGROUND: Overweight and obesity (OWOB) and myopia have become two of the most important issues affecting the health of children and adolescents worldwide. Despite the recognition that the school physical activity (PA) environment is a critical factor for preventing and controlling overweight, obesity (OWOB), and myopia in children and adolescents, research on OWOB and myopia as a comorbidity remains unexplored, with evidence for effective strategies still being inconclusive. Hence, this study aimed to assess the prevalence and progression of comorbid OWOB/myopia and each condition alone, and to explore the association with school PA environment. METHODS: A total of 9814 children and adolescents aged 6-18 years were included from the Chinese National Survey on Students' Constitution and Health follow-up survey conducted from November 2019 to November 2020 in China. Anthropometric measurements, unaided distance vision acuity and non-cycloplegic refraction data were collected to assess OWOB and myopia, while eight indicators from questionnaires for children and adolescents aged 9-18 years were investigated to assess school PA environment. We calculated the one-year incidence and progression rates of comorbid OWOB/myopia, OWOB alone, and myopia alone. Mixed effect logistic regression was evaluated the association between school PA environment and incidence and progression of comorbid OWOB/myopia, OWOB, and myopia. RESULTS: The prevalence of comorbid OWOB/myopia increased from 11.1% in 2019 to 17.9% in 2020, and the incidence of comorbid OWOB/myopia was 10.9%. Children and adolescents experiencing an unfavorable school PA environment had a higher risk of the incidence of comorbid OWOB/myopia compared to a favorable school environment (OR = 1.85, 95% CI: 1.42-2.42). Similar findings were seen in the incidence of obesity (OR = 1.86, 95% CI: 1.26-2.75). Children and adolescents in an unfavorable school PA environment had a higher risk of myopia progression (OR = 1.29, 95% CI: 1.01-1.65). CONCLUSIONS: Obesity and myopia and their comorbidity have been serious among children and adolescents in China. A favorable school PA environment might mitigate the risk of comorbid OWOB/myopia, OWOB, and myopia progression.

Lean body mass positively associate with blood pressure in Chinese adults: the roles of ages and body fat distribution.

BACKGROUND: The relationship between lean body mass (LBM) and blood pressure (BP) is controversial and limited. This study investigated the associations between LBM indexes and BP in adults of different ages and with varying body fat distribution. METHODS: The data for the present analysis was obtained from a cross-sectional survey of 1,465 adults (50.7% males) aged 18-70 years conducted in Beijing, China. Regional LBM and fat distribution, including fat mass (FM) and android to gynoid fat ratio (AOI), were assessed using a dual-energy X-ray bone densitometer. Generalized Liner Model (GLM) was employed. Confounders, including age, sex, height, weight, smoking, and alcohol use, were evaluated through questionnaires and physical examinations. RESULTS: Males had higher rates of hypertension (11.19% vs. 4.92%) and prehypertension (21.57% vs. 14.59%) than females. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 122.04 mmHg and 76.68 mmHg. There were no significant associations between LBM and DBP (p > 0.05). However, arms LBM (ß = 1.86, 95% CI: 0.77, 2.94) and trunk LBM (ß = 0.37, 95% CI: 0.01, 0.73) were significantly associated with SBP. The association of LBM on DBP was stronger with increasing ages, and stronger in females than in males (p < 0.001). The association between adults' arms LBM and SBP was stronger in the high level FM group (ß = 2.74 vs. ß = 1.30) and high level AOI group (ß = 1.80 vs. ß = 2.08). CONCLUSION: The influence of LBM on SBP increases with age, particularly after the age twenty years in females. For adults with high FM or high AOI, LBM in the arms, showed a stronger positive predictive association with SBP. This suggests that, in addition to controlling fat content, future efforts to improve cardiovascular health in adults should include the management of LBM (especially in the upper body).

Long-term exposure to exogenous phthalate, masculinity and femininity trait, and gender identity in children: a Chinese 3-year longitudinal cohort study.

BACKGROUND: Phthalate esters (PAEs) are known to have hormone-like properties, and there is a growing trend of children expressing a gender identity different from assigned sex. However, there has been limited research in the potential links between PAEs exposure and gender identity. METHODS: A total of 571 children (278 boys) completed the follow-up from Oct 2017 to Oct 2020 in Childhood Blood Pressure and Environmental Factors (CBPEF) cohort in Xiamen, China. Urinary PAE metabolites were measured at three time of visits using ultraperformance liquid chromatography-tandem mass spectrometry. The Children's Sex Role Inventory scale was used to assess gender identity (masculinity, femininity, androgyny and undifferentiated), and Tanner definition was used to define puberty timing. Generalized linear models and log-binomial regression were used to assess the relationships between PAEs exposure, gender trait scores and gender identity. RESULTS: Overall, the concentration of most PAEs in more than 90% of participants was above the limit of detection values. In visit 1, there were 10.1% boys with femininity and 11.3% girls with masculinity; while these figures increased to 10.8% and 12.3% during follow-up, respectively. Early puberty onset accounted for 24.8% and 25.6% among boys and girls. Long-term exposure to mono-2-ethylhexyl phthalate (MEHP) (ß = 1.20, 95%CI = 0.13, 2.28), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (ß = 1.25, 95%CI = 0.22, 2.28) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 1.40, 95%CI = 0.24, 2.56) was associated with the increased differences of femininity trait scores in boys who enter puberty earlier, prolonged exposure to di(2-ethylhexyl) phthalate (DEHP) might also have such a positive impact (ß = 1.38, 95%CI = 0.36, 2.41). For gender identity, persistent exposure to low molecular weight phthalates (LMWP) was negatively associated with undifferentiated type among boys entering puberty earlier (RR = 0.18, 95%CI = 0.05, 0.75, P < 0.05), and most of the PAE metabolites exposures showed risk ratios > 1 for their femininity. CONCLUSION: Long-term exposure to PAEs increase the femininity trait scores in boys with early onset of puberty. Although the mechanisms remain to be determined, environmental pollution might have subtle, yet measurable effects on childhood gender identity. Reducing these chemicals exposure has important public implications on gender development.

Disparity in spectrum of infectious diseases between in-school and out-of-school children, adolescents, and youths in China: findings from a successive national surveillance from 2013 to 2021.

Background: An accelerated epidemiological transition, economic development and urbanization have brought rapid reductions but a potential disparity in infectious diseases burdens in-school and out-of-school children, adolescents, and youths in China. This paper assesses the disparity in spectrum of infectious diseases between two groups, and described disparity's variation by age, year and province, and determined the priority diseases. Methods: A total of 7,912,274 new incident cases (6,159,021 in school and 1,753,253 out of school) aged 6-21 years across 43 notifiable infectious diseases have been collected based on China's Notifiable Infectious Disease Surveillance System from 2013 to 2021. All infectious diseases are categorized into seven categories: vaccine preventable, bacteria, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. We used the index of incidence rate ratio (IRR) of by specific disease, category, year, and age to assess the disparity between those out-of-school and in-school, and determine their separate priority diseases. Findings: From 2013 to 2021, a small disparity of notifiable infectious diseases existed with higher average yearly incidence for out-of-school children, adolescents, and youth than that in-school (327.601 v.s. 319.677 per 100,000, IRR = 1.025, 95%CI: 1.023-1.027, standardized IRR = 1.169, 95%CI: 1.155-1.183), and it gradually narrowed by surveillance years with IRR from 1.351 in 2013 to 1.015 in 2021 due to large decreased disparity in compulsory education stage group. Such disparity was mainly driven by sexually transmitted and bloodborne diseases, bacteria diseases, vectorborne diseases, quarantinable diseases and zoonotic diseases. However, vaccine preventable diseases, gastrointestinal and enterovirus diseases showed higher incidence of infectious diseases for those in-school than that out-of-school, particularly for seasonal influenza, mumps and hand-foot-and-mouth disease. Meanwhile, such disparity is obvious in most of ages and in eastern and coastal regions of China, and the narrowing trend is attributed to six categories diseases, except for sexually transmitted and bloodborne diseases with gradually widened disparity between two groups with surveillance years with IRR from 22.939 in 2013 to 23.291 in 2021 due to large disparity for those who have completed compulsory education. Interpretation: A huge achievement has been achieved in reducing the burden and disparity of infectious diseases between out-of-school and in-school children, adolescents, and youths in China, particularly for the compulsory education stage population. The priorities for the coming decades will be to extend successful strategies to a broad scope and promote education, particularly for the investment of social health resources and the improvement of personal health literacy in the non-compulsory education stage. This should involve extending the years of compulsory school, improving sex health education, strengthening monitoring, expanding immunization programs coverage and prioritizing the prevention and control of sexually transmitted diseases and tuberculosis among out-of-school population. Funding: National Natural Science Foundation of China and Beijing Natural Science Foundation.

A bifunctional anti-PCSK9 scFv/Exendin-4 fusion protein exhibits enhanced lipid-lowering effects via targeting multiple signaling pathways in HFD-fed mice.

Fusion protein which encompasses more than one functional component, has become one of the most important representatives of macromolecular drugs for disease treatment since that monotherapy itself might not be effective enough to eradicate the disease. In this study, we sought to construct a bifunctional antibody fusion protein by fusing anti-PCSK9 scFv with Exendin-4 for simultaneously lowering both LDL-C and TG. Firstly, three Ex4-anti-PCSK9 scFv fusion proteins were constructed by genetically connecting the C-terminal of Exendin-4 to the N-terminal of anti-PCSK9 scFv through various flexible linker peptides (G4S)n (n = 2, 3, 4). After soluble expression in E. coli, the most potent Ex4-(G4S)4-anti-PCSK9 scFv fusion protein was selected based on in vitro activity assays. Then, we investigated the in vivo therapeutic effects of Ex4-(G4S)4-anti-PCSK9 scFv on the serum lipid profile and bodyweight changes as well as underlying molecular mechanism in HFD-fed C57BL/6 mice. The data showed that Ex4-(G4S)4-anti-PCSK9 scFv exhibits enhanced effects of lowering both LDL-C and TG in serum, reducing food intake and body weight via blocking PCSK9/LDLR, activating AMPK/SREBP-1 pathways, and up-regulating sirt6. Conclusively, Ex4-(G4S)4-anti-PCSK9 has the potential to serve as a promising therapeutic agent for effectively treating dyslipidemia with high levels of both LDL-C and TG.

Persistent high exposure to exogenous phthalates and endogenous sex hormones associated with early pubertal onset among children: A 3.5-year longitudinal cohort study in China.

BACKGROUND: Early onset of puberty could have significant impacts on childhood health, but the extent to which it was affected by phthalate esters (PAEs) and sex hormone disruption was not understood. The aim of this study is to investigate the associations between exposure to PAEs and sex hormone disruption and early onset of puberty in children. METHODS: A longitudinal cohort study was conducted in China from May 2017 to Oct 2020, involving 740 children during consecutive visits. The onset of puberty was evaluated using Tanner definition, and early puberty was defined as an onset age less than the first 25 %, with cut-offs of 10.33 and 8.97 years for boys and girls, respectively. Serum testosterone (TT), estradiol (E2) and urinary PAE metabolites were measured during three visits. Generalized linear models were used to explore the associations between PAE and sex hormones with the age of puberty onset, while log-binomial regressions were applied to assess the associations of persistent exposure to PAEs and sex hormones with early pubertal onset. RESULTS: Approximately 86.0 % of boys and 90.2 % of girls completed puberty onset from pre-puberty, and more than 95 % of participants had PAE concentrations higher than the limit of detection. Boys showed higher exposure to PAE pollutants and higher TT levels. Persistent exposure to PAEs was positively associated with early pubertal onset in girls (ARR = 1.97, 95 %CI = 1.12, 3.46). Moreover, persistent exposure to PAEs and E2 had synergistic associations with early pubertal onset in both boys (ARR = 4.77, 95 %CI = 1.06, 21.54) and girls (ARR = 7.07, 95 %CI = 1.51, 33.10). However, PAEs and TT had antagonistic associations only in boys (ARR = 0.44, 95 %CI = 0.07, 2.58). CONCLUSION: Long-term exposure to PAEs might increase the risk of early pubertal onset, and it appears to work in synergy with E2, while in antagonism with TT in boys' early pubertal onset. Reducing PAEs exposure might promote pubertal health.

Association of SO2/CO exposure and greenness with high blood pressure in children and adolescents: A longitudinal study in China.

Introduction: We aimed to investigate the association between greenness around schools, long-term gaseous air pollution exposure (SO2 and CO), and blood pressure in children and adolescents. Methods: From 2006 to 2018, a total of 219,956 Chinese children and adolescents aged 7-17 years in Beijing and Zhongshan were included in this longitudinal study. Annual average concentrations of SO2 and CO and the mean values of normalized difference vegetation index around schools were calculated. We used the generalized estimation equation model, restricted cubic spline model, and Cox model to analyze the health effects. Results: Among all the subjects, 52,515 had the first onset of HBP. During the follow-up, HBP's cumulative incidence and incidence density were 23.88% and 7.72 per 100 person-year respectively. Exposures to SO2 and CO were significantly associated with SBP [ß = 1.30, 95% CI: (1.26, 1.34) and 0.78 (0.75, 0.81)], DBP [ß = 0.81 (0.79, 0.84) and 0.46 (0.44, 0.48)] and HBP [HR = 1.58 (1.57, 1.60) and 1.42 (1.41, 1.43)]. The risks of HBP attributed to SO2 and CO pollution would be higher in school-aged children in the low greenness group: the attributable fractions (AFs) were 26.31% and 20.04%, but only 13.90% and 17.81% in the higher greenness group. The AFs were also higher for normal-BMI children and adolescents in the low greenness group (AFs = 30.90% and 22.64%, but 14.41% and 18.65% in the high greenness group), while the AFs were not as high as expected for obese children in the low greenness group (AFs = 10.64% and 8.61%), nor was it significantly lower in the high greenness group (AFs = 9.60% and 10.72%). Discussion: Greenness could alleviate the damage effects of SO2/CO exposure on the risks of HBP among children and adolescents, and the benefit is BMI sensitivity. It might offer insights for policymakers in making effective official interventions to prevent and control the prevalence of childhood HBP and the future disease burden caused by air pollution.

Enhancing the effectiveness of infectious disease health education for children and adolescents in China: a national multicenter school-based trial.

BACKGROUND: Infectious diseases pose a significant risk to the health and well-being of children and adolescents, and can even be life-threatening. Thus, our study aimed to explore the effectiveness of health education based on the social-ecological model in improving the knowledge of infectious diseases among this vulnerable population. METHODS: This study was a school-based intervention conducted in seven Chinese provinces in 2013, involving a total of 26,591 children and adolescents in the intervention group and 24,327 in the control group. The intervention group received a comprehensive health intervention based on the social-ecological model (SEM) over six months, which included a supportive environment, health education on infectious diseases, guidance on self-monitoring infectious disease-related behaviors, and other measures. Data on infectious disease-related knowledge and other characteristics were collected through questionnaires. The main outcome measure will be the difference in the effectiveness of health education regarding infectious diseases in children and adolescents between baseline and post-intervention. A mixed-effects regression model was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the impact of infectious disease-related interventions on the participants. RESULTS: We utilized a socioecological model as the foundation for a six-month health education program on infectious diseases targeting children and adolescents in the intervention group. At the individual and community levels, the correct rate of health behavior related to infectious diseases in the intervention group was higher than that in the control group (P < 0.05), the ORs (95% CI) were 0.94 (0.90-0.99) and 0.94 (0.89-0.99), respectively. But the intervention effect was not significant at the interpersonal level. The intervention effect at the organizational level was obvious, with an increase in opportunities for children and adolescents to acquire knowledge of infectious diseases from courses and lectures, teachers, and doctors, (all P < 0.05), with the ORs (95% CI) of 0.92 (0.87-0.97) and 0.86 (0.83-0.94), respectively. However, there was no significant difference between the intervention group and the control group in school infectious disease health education policy. CONCLUSION: Enhancing health education regarding infectious diseases is crucial in promoting comprehensive prevention and control measures among children and adolescents. Nevertheless, it remains imperative to reinforce health education on infectious diseases at the interpersonal and policy levels. This holds significant reference value for mitigating childhood infectious diseases in the post-COVID-19 era.

Sleep time and quality associated with depression and social anxiety among children and adolescents aged 6-18 years, stratified by body composition.

BACKGROUND: Sleep has been suggested as risk factors for depression and social anxiety in children and adolescents, but little is known about the role of individual body composition on these association. METHOD: We conducted a cross-sectional survey of children and adolescents aged 6-18 years in Beijing, China, in 2020, and assessed body composition by using iDXA dual-energy X-ray bone densitometer. Generalized liner model (GLM) and restricted cubic spline (RCS) were employed to analyze the associations between sleep and depression and social anxiety with different body composition. The attributable fraction (AFs) to assess the benefits of improvements of sleep in reducing depression and social anxiety odds. RESULTS: Depression and social anxiety accounted for 13.1 % and 30.3 % of the study population. Sleep time was significantly associated with depression (HR = 2.35[1.58, 3.50]), and social anxiety (HR = 1.65[1.24, 2.20]); and sleep quality was significantly associated with depression (HR = 7.27[4.87, 10.84]), and social anxiety (HR = 2.54 [1.99, 3.25]) among children and adolescents. The exposure to both insufficient sleep time and poor sleep quality were associated with a higher odd of depression and social anxiety, but lower BF%, higher muscle rate and FFM/FM alleviated the adverse effects of sleep quality on depression and social anxiety. LIMITATIONS: Conclusions about causality remain speculative because of the cross-sectional design. CONCLUSION: Insufficient sleep time, poor sleep quality, high BF%, low muscle rate and FFM/FM can jointly associate with anxiety and depression. This study provides new evidence support for accurate prevention and control of mental diseases in children and adolescents with different body types.

Weight self-misperception and obesity-related knowledge, attitudes, lifestyle behaviours and cardio-metabolic markers among Chinese school-aged children and adolescents.

OBJECTIVE: The relationships between childhood weight self-misperception and obesity-related factors particularly health markers have not been extensively discussed. This study aims to examine the associations between weight self-misperception and obesity-related knowledge, attitudes, lifestyles and cardio-metabolic markers among Chinese paediatric population. DESIGN: Cross-sectional study. SETTING: Data sourced from a national survey in Chinese seven provinces in 2013. PARTICIPANTS: Children and adolescents aged 5-19 years. RESULTS: Of the total 14 079 participants, there were 14·5 % and 2·2 % participants over-estimated and under-perceived their weight, respectively. Multi-variable logistic regression was applied to calculate OR and 95 % CI (95 % Cl) of obesity-related behaviours and cardio-metabolic markers by actual and perceived weight status. Individuals who perceived themselves as overweight/obese were more likely to have prolonged screen time, insufficient dairy intake and over sugar-sweetened beverages consumption (all P < 0·05), regardless of their weight. Furthermore, actual overweight/obese individuals had higher odds of abnormal cardio-metabolic markers, but a smaller magnitude of association was found among weight under-estimators. Among non-overweight/obese individuals, weight over-estimation was positively associated with abdominal obesity (OR: 10·49, 95 % CI: 7·45, 14·76), elevated blood pressure (OR: 1·30, 95 % CI: 1·12, 1·51) and dyslipidemia (OR: 1·43, 95 % CI: 1·29, 1·58). CONCLUSIONS: Weight over-perception was more prevalent than under-estimation, particularly in girls. Weight over-estimators tended to master better knowledge but behave more unhealthily; both weight over-perception and actual overweight/obesity status were associated with poorer cardio-metabolic markers. Future obesity intervention programmes should additionally pay attention to the population with inaccurate estimation of weight who were easily overlooked.

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.

Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation.

Xanthine dehydrogenase (XDH) is the rate-limiting enzyme in purine catabolism by converting hypoxanthine to xanthine and xanthine to uric acid. The altered expression and activity of XDH are associated with the development and prognosis of multiple types of cancer, while its role in lung adenocarcinoma (LUAD) remains unknown. Herein, we demonstrated that XDH was highly expressed in LUAD and was significantly correlated with poor prognosis. Though inhibition of XDH displayed moderate effect on the viability of LUAD cells cultured in the complete medium, it significantly attenuated the survival of starved cells. Similar results were obtained in XDH-knockout cells. Nucleosides supplementation rescued the survival of starved LUAD cells upon XDH inhibition, while inhibition of purine nucleoside phosphorylase abrogated the process, indicating that nucleoside degradation is required for the XDH-mediated survival of LUAD cells. Accordingly, metabolic flux revealed that ribose derived from nucleoside fueled key carbon metabolic pathways to sustain the survival of starved LUAD cells. Mechanistically, down-regulation of XDH suppressed unfolded protein response (UPR) and autophagic flux in starved LUAD cells. Inhibition of XDH decreased the level of amino acids produced by autophagic degradation, which was accompanied with down-regulation of mTORC1 signaling. Supplementation of amino acids including glutamine or glutamate rescued the survival of starved LUAD cells upon knockout or inhibition of XDH. Finally, XDH inhibitors potentiated the anti-cancer activity of 2-deoxy-D-glucose that induced UPR and/or autophagy in vitro and in vivo. In summary, XDH plays a crucial role in the survival of starved LUAD cells and targeting XDH may improve the efficacy of drugs that induce UPR and autophagy in the therapy of LUAD.

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.

Association between time spent on digital devices and body weight overestimation in children and adolescents / 中国学校卫生

Objective@#To explore the association between digital devices usage and body weight overestimation in children and adolescents aged 7-18, in order to provide a scientific basis for body weight overestimation prevention in children and adolescents.@*Methods@#Based on the data of the Research Special Project for Public Welfare Industry of Health using stratified cluster sampling method in 2012, a tatal of 40 073 children and adolescents from 7 provinces with complete information were chosen. Ordinal multivariable Logistic regression model estimated the association between digital devices usage and body weight overestimation.@*Results@#A total of 4 276(11.8%) students with overestimation of body weight were detected, who spent >300 min/d time in digital devices(5.12%) than others (3.84%)( χ 2=19.14, P <0.01). Univariate analysis showed that students with time spent on digital devices >300 min/d had a higher risk in overestimation of body weight ( OR=1.36,95%CI=1.18-1.57,P <0.01) compared with students who spent on digital devices≤120 min/d. There was still a significant association after confounder adjustment ( OR=1.28, 95%CI= 1.10-1.48,P <0.05). Stratified analysis showed that the association between digital devices usage and overestimation of body weight were only observed in girls, 11-18 years old and non single child( P <0.05).@*Conclusion@#The time usage of digital devices is associated with overestimation of body weight in children and adolescents. It may helpful for children and adolescents to prevent overestimation of body weight by reducing time spent on digital devices.