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Abstract Background Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. Methods Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. Results Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P

BackgroundResearch on how the physical activity home environment affects fundamental movement skills (FMS) in preschool children in China is limited. However, the role of moderate-to-vigorous physical activity (MVPA) in this relationship is still unclear. This study aims to analyze gender differences in FMS, explore associations between the physical activity home environment, MVPA, and FMS, and investigate MVPA's mediating role in these relationships.MethodsWe recruited 169 preschool children (95 boys, 74 girls; mean age 4.9 years) from four kindergartens in Hengyang, China. The Family Environment Scale on Motor Development for Preschool Urban Children (FESMPD) assessed physical activity home environment. Objective measurement of MVPA used ActiGraph wGT3-BT accelerometers. The Test of Gross Motor Development-3 (TGMD-3) evaluated FMS. Statistical analyses were conducted using the PROCESS macro in SPSS, with sociodemographic variables as controls.ResultsBoys exhibited significantly higher levels of MVPA, parenting style, locomotor skills, and object control skills compared to girls (P

Abstract Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes‐associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Purposes Orthopedic insoles are an effective means of non-surgical correction of flatfoot, but there is no unified view on its rehabilitation mechanism, and most previous studies have focused on the improvement of plantar pressure. Methods Firstly, a 3D motion capture system, a force platform and a foot test system were used to test the subjects respectively, to obtain the kinematic and dynamic data of the flatfoot patients' lower limbs when walking naturally, and then Anybody software was used to establish the musculoskeletal model of the subjects and carry out inverse kinetic analysis, to compare and analyse the joint angles of the lower limbs, the ground reaction force, and the changes in parameters such as joint moment and muscle activation, etc. of the lower limbs of the patients with flatfoot when they walked naturally before and after the use of orthopaedic insoles, joint moments and muscle activation during natural walking before and after using orthotic insoles. Findings The results show that after wearing the orthopedic insoles, the plantar pressure distribution of flatfoot patients is im proved significantly, the ankle joint motion angle changed significantly during the walking cycle, the peak vertical and lateral ground reaction forces became smaller during the support period, and the joint moments and the activation of major muscles in the lower limbs change to different degrees. Conclusions This study may provide a valuable reference for the rehabilitation treatment of flatfoot patients in clinic.

Abstract The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

The Grain for Green Program and soil and water conservation engineering initiatives are crucial for controlling erosion in steep-slope agriculture. However, it is still unclear how these two management methods should be carried out in respect to the situation in mountainous areas. Therefore, taking a typical mountainous area in southwest China as an example, we simulated six scenarios in order to compare the food provisioning service (FPS) and soil conservation service of the Grain for Green Program (converting to grassland) and Construction Measures (converting to sloping terrace) under different slopes. Results showed that when farmland with a >25° slope was converted into grassland, the amount of soil erosion (M) decreased by 21.0%, while FPS decreased by only 0.7%. However, when farmland with a >25° slope was converted into sloping terrace, M decreased by 31.3% while FPS increased by 18.7%. With the increases of farmland slope ranges in the Construction Measures scenario, M gradually decreased and FPS gradually increased. Particularly when farmland >15° was converted into sloping terrace, M decreased by 63.9% and FPS increased by 52.7%. Furthermore, the trade-offs of Construction Measures are lower than that of Grain for Green on different slope ranges. Therefore, we conclude that Construction Measures are a more suitable method in mountainous areas than the Grain for Green, and we suggest that further research be conducted to consider the ecological risks of construction engineering measures.

Objective This study aims to explore the current cognitive status and identify risk factors associated with cognitive function in Tibetan hypertensive patients living at various altitudes.Methods The Simple Mental Status Scale (MMSE) was used to evaluate the cognitive function of 611 Tibetan hypertensive patients at various altitudes in Gannan Tibetan Autonomous Prefecture. Afterward, we conducted an analysis to identify the factors influencing their cognitive function.Results The study found that the prevalence of cognitive dysfunction was 22.3%, with a higher incidence at high altitude (group D 29.0%) compared to low altitude (group A 16.0%). The study conducted a binary logistic regression analysis to identify the risk factors for cognitive dysfunction. The analysis revealed that altitude, age, body mass index, marital status, education, income level, and blood pressure control level were all significant risk factors. After controlling for age, body mass index, marital status, educational level, income level, and blood pressure control level, the risk of developing cognitive dysfunction was 2.773 times higher (p

Adipose tissue is composed of adipocytes, stromal vascular fraction, nerves, surrounding immune cells, and the extracellular matrix. Under various physiological or pathological conditions, adipose tissue shifts cellular composition, lipid storage, and organelle dynamics to respond to the stress; this remodeling is called “adipose tissue plasticity”. Adipose tissue plasticity includes changes in the size, species, number, lipid storage capacity, and differentiation function of adipocytes, as well as alterations in the distribution and cellular composition of adipose tissue. This plasticity has a major role in growth, obesity, organismal protection, and internal environmental homeostasis. Moreover, certain thresholds exist for this plasticity with significant individualized differences. Here, we comprehensively elaborate on the specific connotation of adipose tissue plasticity and the relationship between this plasticity and the development of many diseases. Meanwhile, we summarize possible strategies for treating obesity in response to adipose tissue plasticity, intending to provide new insights into the dynamic changes in adipose tissue and contribute new ideas to relevant clinical problems.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

The 24-h movement behavior of preschoolers comprises a spectrum of activities, including moderate-to-vigorous intensity physical activity (MVPA), light-intensity physical activity (LPA), screen-based sedentary behavior (SCSB), non-screen-based sedentary behavior (NSCSB), and sleep. While previous research has shed light on the link between movement behaviors and children’s mental health, the specific impacts on the unique demographic of Chinese preschoolers remain underexplored. This study significantly contributes to the literature by exploring how 24-h movement behavior affects the mental health of preschoolers in a Chinese context. The study involved205 Chinese preschool children (117 boys and 88 girls) between the ages of 3 and 6 years wore accelerometers to measure their LPA, MVPA, and sedentary behavior (SB), while their parents reported the time spent on sleep and SCSB. The parents also completed the Strength and Difficulties Questionnaire to assess their children’s mental health. The study used compositional regression and isotemporal substitution models to examine the relationship between the various components of 24-h movement behavior and mental health. The results showed that greater NCSSB compared to MVPA, LPA, sleep, and SCSB was associated with good prosocial behavior and lower scores on externalizing problems. This highlights the potential of NSCSB as a beneficial component in the daily routine of preschoolers for fostering mental well-being. Replacing 15 min of sleep and SCSB with 15 min of NSCSB was associated with a decrease of 0.24 and 0.15 units, respectively, in externalizing problems. Reallocating 15 min of sleep to NSCSB was linked to an increase of 0.11 units in prosocial behavior. There were no significant substitution effects between LPA and MVPA time with any other movement behavior on prosocial behavior and externalizing problems. Given the positive associations observed, further longitudinal studies are necessary to explore the link between 24-h movement behavior and mental health in preschool children.

BackgroundLimited research has explored the relationship between adhering to 24-h Movement Behaviour guidelines and mental health in Chinese preschool children. The objectives of this study encompassed two primary goals: (1) to investigate the adherence of preschool children in China to the 24-h Movement Behaviour guidelines; and (2) to analyze the relationship between fulfilling various combinations of these guidelines and mental health, identifying the most advantageous combination.MethodsUtilizing a convenience sampling approach, this study included 205 preschool children (117 boys and 88 girls, average age 4.8 ± 0.51 years) from five kindergartens in Hengyang, Hunan Province. The physical activity (PA) and sedentary behaviour of preschool children were objectively assessed using waist-worn accelerometers, while sleep duration and screen time were reported by the children's parents. To evaluate mental health, the parent version of the internationally validated Strength and Difficulties Questionnaire (SDQ) was employed, which measures externalizing problems, internalizing problems, and prosocial behaviour. Employing Mplus 8.0 for Structural Equation Modeling analysis, while controlling for demographic variables, the study explored the connection between preschool children's mental health and their adherence to the 24-h Movement Behaviour guidelines.ResultsWorryingly, merely 14.6% of preschoolers met the recommended guidelines for all three aspects (PA, sleep duration, and screen time). Positive correlations were identified between meeting PA guidelines and displaying prosocial behaviour (β = 0.184; p