19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

BACKGROUND: The urban-rural disparities in overweight and obesity among children and adolescents are narrowing, and there is a need for long-term and updated data to explain this inequality, understand the underlying mechanisms, and identify priority groups for interventions. METHODS: We analyzed data from seven rounds of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted from 1985 to 2019, focusing on school-age children and adolescents aged 7-18 years. Joinpoint regression was used to identify inflection points (indicating a change in the trend) in the prevalence of overweight and obesity during the study period, stratified by urban/rural areas and sex. Annual percent change (APC), average annual percent change (AAPC), and 95% confidence interval (CI) were used to describe changes in the prevalence of overweight and obesity. Polynomial regression models were used to predict the prevalence of overweight and obesity among children and adolescents in 2025 and 2030, considering urban/rural areas, sex, and age groups. RESULTS: The prevalence of overweight and obesity in urban boys and girls showed an inflection point of 2000, with AAPC values of 10.09% (95% CI: 7.33-12.92%, t = 7.414, P <0.001) and 8.67% (95% CI: 6.10-11.30%, t = 6.809, P <0.001), respectively. The APC for urban boys decreased from 18.31% (95% CI: 4.72-33.67%, t = 5.926, P = 0.027) to 4.01% (95% CI: 1.33-6.75%, t = 6.486, P = 0.023), while the APC for urban girls decreased from 13.88% (95% CI: 1.82-27.38%, t = 4.994, P = 0.038) to 4.72% (95% CI: 1.43-8.12%, t = 6.215, P = 0.025). However, no inflection points were observed in the best-fit models for rural boys and girls during the period 1985-2019. The prevalence of overweight and obesity for both urban and rural boys is expected to converge at 35.76% by approximately 2027. A similar pattern is observed for urban and rural girls, with a prevalence of overweight and obesity reaching 20.86% in 2025. CONCLUSIONS The prevalence of overweight and obesity among Chinese children and adolescents has been steadily increasing from 1985 to 2019. A complete reversal in urban-rural prevalence is expected by 2027, with a higher prevalence of overweight and obesity in rural areas. Urgent action is needed to address health inequities and increase investments, particularly policies targeting rural children and adolescents.
Humans ; Child ; Adolescent ; Female ; Male ; Rural Population/statistics & numerical data* ; Overweight/epidemiology* ; Prevalence ; China/epidemiology* ; Pediatric Obesity/epidemiology* ; Obesity/epidemiology* ; Urban Population

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.

Objective:To describe the prevalence of psychological distress and to analyze its influencing factors among Chinese children and adolescents aged 9-18 years in 2019.Methods:Data was from the 2019 Chinese National Survey on Students' Constitution and Health, and 148 892 children and adolescents were included. Psychological distress was measured using the Kessler Psychological Distress Scale (K10): scores ≤19 were defined as no psychological distress, scores between 20-24 were defined as mild psychological distress, scores between 25-29 were defined as moderate psychological distress, and scores ≥30 were defined as severe psychological distress (moderate to severe psychological distress were defined as high psychological distress). The ANOVA, t test, and χ2 test were used to compare the differences in K10 scores and high psychological distress rates among children and adolescents with different characteristics. The ANOVA and trend χ2 test were used to analyze the trends. Modified-Poisson regression models were used to determine influencing factors of high psychological distress. Results:The K10 scores for Chinese children and adolescents aged 9-18 years in 2019 was 21.5±9.2, and their rate of high psychological distress was 31.6%. The rates of high psychological distress among children and adolescents aged 9-12, 13-15, and 16-18 years were 22.3%, 35.9%, and 38.8%. K10 scores and rates of high psychological distress showed an increasing trend as age increased (trends test all P<0.001). K10 scores and rates of high psychological distress were higher among children and adolescents who were older, female, rural, in areas with medium to low GDP per capita level, and with lower parental education (all P<0.001). Multifactorial modified-Poisson regression analysis showed that children and adolescents aged 13-15 years, 16-18 years, female, rural, and in areas with low to moderate GDP per capita level were at higher risk of high psychological distress (all P<0.05), with a OR (95% CI) of 1.55 (1.52-1.58), 1.66 (1.63-1.69), 1.07 (1.05-1.09), 1.02 (1.01-1.04), 1.10 (1.07-1.12). Children and adolescents in areas with medium to high GDP per capita level, whose father had a secondary or high school degree, whose father had a college degree or above, whose mother had a secondary or high school degree, and whose mother had a college degree or above were at lower risk of high psychological distress (all P<0.05), with a OR (95% CI) of 0.96 (0.94-0.98), 0.92 (0.90-0.93), 0.84 (0.82-0.86), 0.95 (0.93-0.97), 0.86 (0.83-0.88). Conclusions:The prevalence of psychological distress was high among Chinese children and adolescents aged 9-18 years in 2019, which is a vital problem. Mental health interventions need to be implemented among children and adolescents that were older, girls, rural, live in areas with lower economic levels, and whose parents have a lower education level.

Objective:To analyze the association between the occurrence of spermarche and menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years.Methods:Data were drawn from the 2019 Chinese National Survey on Students' Constitution and Health, and a total of 54 438 boys aged 11 to 18 years and 76 376 girls aged 9 to 18 years with psychological distress, spermarche/menarche records were included in the final analysis. The occurrence of spermarche/menarche was recorded by physicians, and psychological distress was classified according to the Kessler Psychological Distress Scale scores. The chi-square test was used to compare the difference between groups in the occurrence of spermarche/menarche, and the multinomial logistic regression model and stratification analysis was established to analyze the association between psychological distress and spermarche/menarche.Results:The incidence of spermarche/menarche in 2019 ranged from 6.3% to 96.5% for eight age groups of Chinese boys and 2.8% to 99.0% for ten age groups of girls. The rates of high psychological distress among boys and girls were 32.5% and 32.7%. Among boys aged 11 to 18 years, the rate of high psychological distress increased with age, with a trend test P<0.001, and the difference in the rate of high psychological distress between those who had and had not had their spermarche was not statistically significant in all age groups. Among girls aged 9 to 18 years, the rate of high psychological distress increased with age, with a trend P<0.001; the rate of high psychological distress was higher in the group with menarche at age 10 and 12 than in the group without menarche (all P<0.05). High psychological distress was positively correlated with spermarche among boys aged 13-15 years living in urban areas and hight level economic development areas ( OR=1.11, 95% CI: 1.02-1.21; OR=1.18, 95% CI: 1.06-1.32). Overall, high psychological distress was positively correlated with menarche in girls aged 9-12 and 13-15 years ( OR=1.33, 95% CI: 1.25-1.42; OR=1.22, 95% CI: 1.07-1.39). High psychological distress was positively correlated with menarche among girls aged 9-12 years living in different regions except for the Northeast region, in areas with different levels of economic development, and in urban and rural areas, in girls aged 13-15 years living in urban, central, and western regions, and in girls aged 16-18 years residing in the central region. Conclusions:This study found an association between the occurrence of spermarche/menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years in 2019, which was particularly significant among girls aged 9 to 12 years and boys aged 13 to 15 years living in areas with higher levels of socioeconomic development.

Objective:To describe the status of physical fitness of children and adolescents aged 13-18 years in China in 2019 and analyze its association with psychological distress.Methods:Data were drawn from the 2019 Chinese National Survey on Students' Constitution and Health, and 90 633 Han children and adolescents aged 13-18 years were included. Physical fitness was evaluated by "National Students Constitutional Health Standards" (2014 revised edition). Psychological distress was classified according to the scores of the Kessler Psychological Distress Scale: ≤19, 20-24, 25-29, and ≥30 scores indicated no, mild, moderate, and severe psychological distress, respectively, with moderate and severe psychological distress collectively referred to as high psychological distress. The χ2 test was used to compare the distribution differences between boys and girls, the Cochran-Armitage test was used to analyze the trend, and the multinomial logistic regression in the mixed effect model was established to analyze the association between physical fitness and psychological distress. Results:In 2019, the unqualified rate of physical fitness among children and adolescents aged 13-18 years in China was 17.2%, and the prevalence of excellent and good physical fitness was 18.2%, which was lower among boys (15.9%) than girls (20.5%) with a statistically significant difference ( P<0.05). The excellent and good physical fitness rate showed a significantly decreasing trend with age (trend test P<0.05). The rate of high psychological distress among children and adolescents aged 13-18 years in China in 2019 was 39.3%, with boys (37.0%) having a lower prevalence than girls (41.6%), supported by a statistically significant difference ( P<0.05), and a decreasing trend with the degree of physical fitness was observed both in boys and girls (trend test P<0.05). The multinomial logistic regression model showed that the prevalence of moderate ( OR=0.83, 95% CI: 0.79-0.88, P<0.001) and severe ( OR=0.81, 95% CI: 0.77-0.86, P<0.001) psychological distress were both lower in children and adolescents with excellent and good physical fitness. Conclusion:The status of physical fitness and psychological distress of Chinese children and adolescents aged 13-18 in 2019 was not optimistic, with physical fitness showing a significantly negative association with psychological distress.

Objective: To analyze physical fitness and health status and gender differences of middle school students among 5 minorities (Mongolian, Hui, Uyghur, Zhuang and Korean), and to provide the theoretical basis for the strategy formulation. Methods: The present data came from 3 waves of Chinese National Survey on Students Constitution and Health (2010, 2014, and 2019). According to National Standards for Students Physical Health (2014 Revision), excellent, and excellent good physical fitness and health status were defined. Cochran Armitage test was used to examine the trends of physical fitness and health status. Chi square test and Logistic regression were used to analyze the difference of physical fitness and health status by sex and survey year. Results: From 2010 to 2019, the excellent physical fitness and health status rate of Mongolian, Hui, Uyghur, Zhuang and Korean students increased from 1.8%, 0.7%, 0.3%, 0.5% and 1.3% to 4.3%, 2.8%, 1.2%, 1.3% and 3.5%, respectively. The excellent good physical fitness and health status rate of Mongolian, Hui, Uyghur and Zhuang students increased from 12.9%, 8.0%, 7.2 % and 8.4% to 24.7%, 20.1%, 12.6% and 19.8%( Z =6.15，6.71，4.12，3.06，5.26；11.88，13.42，6.70，11.08， P <0.05), respectively. In 2019, students aged 13 to 15 years showed higher proportion of excellent/excellent good physical fitness and health status than that of students aged 16 to 18. Boys were more likely to be in excellent/excellent good physical fitness and health status than girls from 2010 to 2019. The sex difference in excellent/excellent good physical fitness and health status narrowed during 2010 and 2019. Conclusion Physical fitness and health status of minority students improved while sex difference narrowed during last decade, but there is still a long way to reach the goal proposed by China. Targeted intervention should be proposed to promote physical fitness and health status in accordance with the developmental characteristics, especially for girls and students aged 16 to 18 years.

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

Objective: To analyze the long-term trend of the age of spermarche among Chinese Han boys aged 11 to 18 from 2010 to 2019 and its association with nutritional status. Methods: The data from Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019 were used. The age, residence and spermarche of the participants were collected by questionnaire, and their height and weight were measured. A total of 184 633 Han boys aged 11‒18 years with complete data on spermarche, height, and weight were included in this study. The probability regression method was used to calculate the median age (95%CI) at spermarche in different areas, and the trend of age at spermarche in different groups was compared. The multivariate logistic regression model was used to analyze the association between nutritional status and spermarche of Chinese Han boys aged 11‒18 years. Results: The median age of spermarche (95%CI) was 13.85 (13.45-14.22) years old among Chinese Han boys aged 11‒18 years in 2019, with 0.18 years earlier than that in 2010. The median age at spermarche in urban and rural boys was 13.89 and 13.81 years, respectively. Compared with that in 2010, the age at spermarche in urban and rural boys was 0.08 and 0.27 years earlier, respectively. After adjusting for age, province and urban/rural areas, compared with normal weight, spermarche was negatively associated with wasting and positively associated with overweight and obesity, with OR (95%CI) about 0.73 (0.67-0.80), 1.09 (1.02-1.17) and 1.09 (1.01-1.18), respectively. Conclusion: The age of spermarche generally shows an advanced trend among Chinese Han boys and is associated with nutritional status.