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The study aimed to analyze the independent and joint associations of physical activity (PA) and sedentary behavior (SB) with self-rated health (SRH) among Chinese children and adolescents. Cross-sectional data on moderate-to-vigorous physical activity (MVPA), school-based PA, extracurricular physical activity (EPA), screen time (ST), homework time, and SRH were assessed through a self-report questionnaire in the sample of 4227 Chinese children and adolescents aged 13.04 ± 2.62 years. Binary logistic regression was used to compare gender differences in PA, SB, and SRH among children and adolescents, and analyses were adjusted for age and ethnicity. In independent associations, boys and girls engaging in ≥60 min/day of MVPA and >1 hour/day of EPA reported optimal SRH. Only boys who participated in >1 hour/day of school-based PA were significantly more likely to have optimal SRH (OR = 1.49, 95%CI = 1.19-1.86). Only girls who had ≤2 hours/day of ST were significantly associated with optimal SRH (weekdays: OR = 1.38, 95%CI = 1.10-1.74; weekends: OR = 1.40, 95%CI = 1.14-1.71; whole week: OR = 1.42, 95%CI = 1.16-1.73). In joint associations, regardless of SB recommendation, meeting PA recommendation was significantly associated with optimal SRH in both boys (meet PA and SB recommendations, OR = 1.61, 95%CI = 1.03-2.50; meet PA but not SB recommendations, OR = 2.40, 95%CI = 1.57-3.65) and girls (meet PA and SB recommendations, OR = 3.72, 95%CI = 2.08-6.65; meet PA but not SB recommendation, OR = 4.27, 95%CI = 2.09-8.75). Increased PA and reduced SB were positively associated with optimal SRH in Chinese children and adolescents. Notably, lower ST positively influenced only girls' SRH. Meeting PA recommendation is more impactful than meeting SB recommendation for improving SRH in Chinese children and adolescents. Future studies could explore these associations using objective measures of PA and SB in China.

Socioeconomic status (SES) is an important determinant of screen time (ST) in children and adolescents, however, the association between SES and ST is not fully understood in China. This study aimed to investigate the association between SES and ST (operationalized as meeting the ST guidelines; no more than 2 hours per day) in Chinese children and adolescents. Cross-sectional data of 2,955 Chinese children and adolescents aged 8 to 17(53.4% girls) were used. SES was measured using indicators of parental education and perceived family wealth. ST was assessed with detailed items from the Health Behaviour School-aged Children survey questionnaires. Descriptive statistics and a Chi-square test were used to report the sample characteristics and analyse ST differences across different sociodemographic groups. A binary logistic regression was then applied to analyse the association of SES indicators with ST in children and adolescents. Overall, 25.3% of children and adolescents met the ST guidelines. Children and adolescents with higher parental education levels were 1.84 [95% CI 1.31-2.57; father] and 1.42 [95% CI 1.02-1.98; mother] times more likely to meet the ST guidelines than those with lower parental education levels. Associations between SES and ST varied across sex and grade groups. Moreover, the associations of SES with ST on weekdays and weekends were different. This study demonstrated the association between SES and ST in children and adolescents, highlighting the importance of targeting children and adolescents with low SES levels as an intervention priority. Based on our findings, specific interventions can be tailored to effectively reduce ST. Future studies are encouraged to use longitudinal or interventional designs to further determine the association between SES and ST.

Background Globally, the majority of kindergarten-aged children face obesity issues and insufficient physical activity (PA) engagement. Regular PA participation can provide various health benefits, including obesity reduction, for kindergarten-aged children. However, limited studies have investigated the factors influencing kindergarten-aged children’s PA engagement from the perspective of their teachers. This qualitative study aimed to identify factors that could help promote PA among kindergarten-aged children from teachers’ perspectives, including facilitators, barriers, and teachers’ recommendations. Methods Fifteen kindergarten teachers (age range: 28–50 years; mean age: 38.53 years) with teaching experience ranging from 2 to 31 years (mean: 16.27 years) were recruited from Shanghai municipality, Henan, and Jiangsu provinces in China. One-on-one semi-structured interviews were conducted via face-to-face ( n  = 7) or telephone ( n  = 8) to gather insights into factors influencing PA promotion among kindergarten-aged children. The interviews were audio-recorded, transcribed, and analyzed using a constant comparison approach based on grounded theory, which involved open, axial, and selective coding processes. Results The study revealed mutual theoretical support between themes and the social-ecological model (SEM), as factors identified in the study are distributed at various levels of the SEM. Twelve factors were identified at four levels of the SEM: (1) intrapersonal level (children’s personality and skills), (2) interpersonal level (family, peers, and teachers influence), (3) organizational level (school environment and resources, opportunities for kindergarten teachers’ training and children’s PA, design and organization of PA, and PA that children need), (4) community level (family-school partnerships). Conclusion Various factors at different levels can influence kindergarten-aged children’s PA. The study’s findings revealed that these factors are distributed across the first four levels of SEM, with the majority being at the organizational level. These multilevel findings are expected to assist in developing and implementing more effective PA interventions for kindergarten-aged children. Future research is warranted to identify strategies for promoting PA among kindergarten-aged children at the policy level of the SEM.

Background Self-rated health (SRH) is one of the common measures to evaluate individuals’ overall health. Many studies have explored the associations between different types of physical activity (PA), sedentary behavior (SB), and SRH in children and adolescents. These studies report inconsistent findings and sometimes highlight gender differences. This systematic review aims to synthesize findings to provide a comprehensive evaluation of these associations. Methods English-language articles published between January 2010 and September 2024 were systematically searched through Web of Science, PubMed, and EBSCOhost databases. Following PRISMA guidelines, we included 47 studies in this review that meet eligibility criteria. Study quality was assessed using the National Institutes of Health's study quality assessment tool for observational cohort and cross-sectional studies. Results The majority of study findings show that ≥ 60 min/day of moderate-to-vigorous PA (≥ 4 days/week), vigorous PA (≥ 3 days/week or ≥ 4 times/week), out-of-school PA (≥ 2 days/week), and sports participation are significantly positive associated with SRH. Additionally, evidence suggests that SB (e.g., watching TV and doing homework) generally shows no significant association with SRH. More study findings support that PA is positively associated with boys' SRH than that of girls. Conclusions Findings show significant positive associations between PA and SRH, particularly those of vigorous and moderate-to-vigorous intensity, while the association between SB and SRH requires further investigation beyond TV and video game/computer times. Evidence of gender differences in the associations suggests the potential need for targeted strategies to enhance SRH in girls.

Multiple studies have recognized the involvement of the complement cascade during Alzheimer’s disease pathogenesis. However, the specific role of C5a-C5aR1 signaling in the progression of this neurodegenerative disease is still not clear. Furthermore, its potential as a therapeutic target to treat AD still remains to be elucidated. Canonically, generation of the anaphylatoxin C5a as the result of complement activation and interaction with its receptor C5aR1 triggers a potent inflammatory response. Previously, genetic ablation of C5aR1 in a mouse model of Alzheimer’s disease exerted a protective effect by preventing cognitive deficits. Here, using PMX205, a potent, specific C5aR1 antagonist, in the Tg2576 mouse model of Alzheimer’s disease we show a striking reduction in dystrophic neurites in parallel with the reduced amyloid load, rescue of the excessive pre-synaptic loss associated with AD cognitive impairment and the polarization of microglial gene expression towards a DAM-like phenotype that are consistent with the neuroprotective effects seen. These data support the beneficial effect of a pharmacological inhibition of C5aR1 as a promising therapeutic approach to treat Alzheimer’s disease. Supportive of the safety of this treatment is the recent FDA-approval of another other C5a receptor 1 antagonist, Avacopan, as a treatment for autoimmune inflammatory diseases.

The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer's Disease (AD). Unfortunately, many current Trem2 mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2 (Normal Splice Site) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products. Trem2 mice were treated with the demyelinating agent cuprizone, or crossed with the 5xFAD mouse model of amyloidosis, to explore the impact of the TREM2 R47H variant on inflammatory responses to demyelination, plaque development, and the brain's response to plaques. Trem2 mice display an appropriate inflammatory response to cuprizone challenge, and do not recapitulate the null allele in terms of impeded inflammatory responses to demyelination. Utilizing the 5xFAD mouse model, we report age- and disease-dependent changes in Trem2 mice in response to development of AD-like pathology. At an early (4-month-old) disease stage, hemizygous 5xFAD/homozygous Trem2 (5xFAD/Trem2 ) mice have reduced size and number of microglia that display impaired interaction with plaques compared to microglia in age-matched 5xFAD hemizygous controls. This is associated with a suppressed inflammatory response but increased dystrophic neurites and axonal damage as measured by plasma neurofilament light chain (NfL) level. Homozygosity for Trem2 suppressed LTP deficits and loss of presynaptic puncta caused by the 5xFAD transgene array in 4-month-old mice. At a more advanced (12-month-old) disease stage 5xFAD/Trem2 mice no longer display impaired plaque-microglia interaction or suppressed inflammatory gene expression, although NfL levels remain elevated, and a unique interferon-related gene expression signature is seen. Twelve-month old Trem2 mice also display LTP deficits and postsynaptic loss. The Trem2 mouse is a valuable model that can be used to investigate age-dependent effects of the AD-risk R47H mutation on TREM2 and microglial function including its effects on plaque development, microglial-plaque interaction, production of a unique interferon signature and associated tissue damage.

Background Socioeconomic status (SES) is an important determinant of screen time (ST) in children and adolescents, however, the association between SES and ST is not fully understood in China. This study aimed to investigate the association between SES and ST (operationalized as meeting the ST guidelines; no more than 2 hours per day) in Chinese children and adolescents. Methods Cross-sectional data of 2,955 Chinese children and adolescents aged 8 to 17(53.4% girls) were used. SES was measured using indicators of parental education and perceived family wealth. ST was assessed with detailed items from the Health Behaviour School-aged Children survey questionnaires. Descriptive statistics and a Chi-square test were used to report the sample characteristics and analyse ST differences across different sociodemographic groups. A binary logistic regression was then applied to analyse the association of SES indicators with ST in children and adolescents. Results Overall, 25.3% of children and adolescents met the ST guidelines. Children and adolescents with higher parental education levels were 1.84 [95% CI 1.31–2.57; father] and 1.42 [95% CI 1.02–1.98; mother] times more likely to meet the ST guidelines than those with lower parental education levels. Associations between SES and ST varied across sex and grade groups. Moreover, the associations of SES with ST on weekdays and weekends were different. Conclusions This study demonstrated the association between SES and ST in children and adolescents, highlighting the importance of targeting children and adolescents with low SES levels as an intervention priority. Based on our findings, specific interventions can be tailored to effectively reduce ST. Future studies are encouraged to use longitudinal or interventional designs to further determine the association between SES and ST.

Background In several large genome‐wide association studies (GWAS), genetic polymorphisms of Abi3 have been identified as a risk factor for late‐onset Alzheimer’s Disease (LOAD). ABI3 along with ABI1 and ABI2, regulate the formation of the WAVE complex which in turn, regulates actin dynamics. ABI3 is highly expressed in microglia in the brain, however, the function of ABI3 in microglia is relatively unknown. In recent studies knock‐out of ABI3 has been shown to exacerbate amyloid beta (Aβ) pathology and associated inflammation. To date, there have been no studies on variant specific effects on amyloid beta pathology. Methods To study the effects of ABI3 on the development of Alzheimer’s disease (AD) relevant pathologies we introduced an equivalent coding sequence change that has been identified as a risk variant for LOAD (S212F) into the C57BL/6 mouse genome using CRISPR/Cas9 (S209F). We set out to characterize the Abi3S209F variant and investigate its impact on AD pathology when crossed with 5xFAD transgenic mice, generating four distinct groups: WT, Abi3S209F homozygous, 5xFAD, and 5xFAD/Abi3S209F homozygous. Characterization was performed using histological staining and biochemical approaches at 4‐, 12‐ and 18‐months of age. Results 5xFAD/Abi3S209F mice displayed an age‐related decrease in dense core‐Aβ plaque burden, characterized by reduced Thioflavin‐S staining, accompanied by changes in fibrillar Aβ (OC) staining, in confocal images of both subiculum and visual cortical regions of 5xFAD/Abi3S209F mice compared to 5xFAD mice. Broadly, microglial numbers mimic plaque load, however by 18‐months of age 5xFAD/Abi3S209F mice display dramatic reductions in IBA1+ microglia number – to levels comparable to WT/Abi3S209F homozygous mice, suggesting a general loss of plaque associated microglia. By 12 months of age, Abi3S209F homozygous and 5xFAD/ Abi3S209F mice displayed increased synaptic density, independent of pathology in visual cortex, subiculum and CA1 regions. Conclusions Together, these results characterize the effects of the Abi3S209F missense mutation on 5xFAD‐mediated pathology, specifically in Aβ plaque development, glial morphology, and synapses. Our data suggests that this mutation may affect microglia dynamics in an age‐dependent manner and may result in dysfunctional microglia at later stages of disease.

Background The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer’s Disease (AD). Unfortunately, many current Trem2 R47H mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2 R47H NSS ( N ormal S plice S ite) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products. Methods Trem2 R47H NSS mice were treated with the demyelinating agent cuprizone, or crossed with the 5xFAD mouse model of amyloidosis, to explore the impact of the TREM2 R47H variant on inflammatory responses to demyelination, plaque development, and the brain’s response to plaques. Results Trem2 R47H NSS mice display an appropriate inflammatory response to cuprizone challenge, and do not recapitulate the null allele in terms of impeded inflammatory responses to demyelination. Utilizing the 5xFAD mouse model, we report age- and disease-dependent changes in Trem2 R47H NSS mice in response to development of AD-like pathology. At an early (4-month-old) disease stage, hemizygous 5xFAD/homozygous Trem2 R47H NSS (5xFAD/ Trem2 R47H NSS ) mice have reduced size and number of microglia that display impaired interaction with plaques compared to microglia in age-matched 5xFAD hemizygous controls. This is associated with a suppressed inflammatory response but increased dystrophic neurites and axonal damage as measured by plasma neurofilament light chain (NfL) level. Homozygosity for Trem2 R47H NSS suppressed LTP deficits and loss of presynaptic puncta caused by the 5xFAD transgene array in 4-month-old mice. At a more advanced (12-month-old) disease stage 5xFAD/ Trem2 R47H NSS mice no longer display impaired plaque-microglia interaction or suppressed inflammatory gene expression, although NfL levels remain elevated, and a unique interferon-related gene expression signature is seen. Twelve-month old Trem2 R47H NSS mice also display LTP deficits and postsynaptic loss. Conclusions The Trem2 R47H NSS mouse is a valuable model that can be used to investigate age-dependent effects of the AD-risk R47H mutation on TREM2 and microglial function including its effects on plaque development, microglial-plaque interaction, production of a unique interferon signature and associated tissue damage.