Screening for pathogenic variants in obese cohort using whole-exome sequencing

Objective·To screen mutations of key genes in the leptin-melanocyte stimulating hormone (LEP-MSH) pathway by whole-exome sequencing (WES) in the obese cohort.Methods·A total of 119 obese patients aged 17－65 years old with body mass index (BMI)≥34 kg/m2, who underwent laparoscopic sleeve gastrectomy from January 2011 to July 2019 at Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine were collected. The peripheral blood samples of the research subjects were collected, and whole genome DNA was extracted to perform WES. Bioinformatic methods were applied to detect the mutations in 16 genes in the LEP-MSH pathway (ADCY3, AGRP, BDNF, KSR2, LEP, LEPR, MC3R, MC4R, MCHR1, MRAP2, NTRK2, PCSK1, PHIP, POMC, SH2B1, and SIM1). Rare variants with the minor allele frequency in the total population less than 0.02 and in the East Asian population less than 0.01 in the 1000 Genome (1000G), Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD) were selected for subsequent analysis. Six pieces of prediction software were used to evaluate the deleteriousness of the mutations. Finally, based on the clinical information of each patient, the pathogenicity of all variants was determined according to the guidelines of America College of Medical Genetics and Genomics (ACMG), and only the "pathogenic", "likely pathogenic", and "uncertain significance" variants were retained.Results·A total of 26 variants, 22 kinds of variants were detected in 24 patients from 119 subjects, all of which were heterozygous mutations. The detected variants included 7 in SH2B1 gene (accounting for 26.92% of the total variants), 4 in MCHR1 gene (accounting for 15.38%), 3 in PHIP gene (accounting for 11.53%), 2 in ADCY3 and LEPR genes (accounting for 7.69%, respectively), and 1 in LEP, NTRK2, AGRP, KSR2, MC3R, MC4R, BDNF, and PCSK1 genes, respectively (accounting for 3.85%, respectively). There were 3 patients having the same mutation site in SH2B1 gene, and 2 patients having the same mutation sites in LEPR gene and MCHR1 gene, respectively. In addition, among these mutations, there were 12 ones not included in the East Asian population in 3 public databases, which were novel mutations in the East Asian population, located in SH2B1 (p.V209I, p.R67C, and p.L149F), KSR2 (p.P155T), LEP (p.D106N), LEPR (p.W132R), PHIP (p.K1461R), BDNF (p.N84S), PCSK1 (p.R282W), NTRK2 (p.T732M), MC3R (p.S71P), and MC4R (p.W174X).Conclusion·A total of 22 kinds of rare variations possibly associated with obesity in the LEP-MSH pathway are detected, 12 of which are novel in the East Asian population

Study of Muscle Cell Dedifferentiation after Skeletal Muscle Injury of Mice with a Cre-Lox System

Background: Dedifferentiation of muscle cells in the tissue of mammals has yet to be observed. One of the challenges facing the study of skeletal muscle cell dedifferentiation is the availability of a reliable model that can confidentially distinguish differentiated cell populations of myotubes and non-fused mononuclear cells, including stem cells that can coexist within the population of cells being studied. Methodology/Principal Findings: In the current study, we created a Cre/Lox-β-galactosidase system, which can specifically tag differentiated multinuclear myotubes and myotube-generated mononuclear cells based on the activation of the marker gene, β-galactosidase. By using this system in an adult mouse model, we found that β-galactosidase positive mononuclear cells were generated from β-galactosidase positive multinuclear myofibers upon muscle injury. We also demonstrated that these mononuclear cells can develop into a variety of different muscle cell lineages, i.e., myoblasts, satellite cells, and muscle derived stem cells. Conclusions/Significance: These novel findings demonstrated, for the first time, that cellular dedifferentiation of skeletal muscle cells actually occurs in mammalian skeletal muscle following traumatic injury in vivo. © 2011 Mu et al

Review of advanced road materials, structures, equipment, and detection technologies

As a vital and integral component of transportation infrastructure, pavement has a direct and tangible impact on socio-economic sustainability. In recent years, an influx of groundbreaking and state-of-the-art materials, structures, equipment, and detection technologies related to road engineering have continually and progressively emerged, reshaping the landscape of pavement systems. There is a pressing and growing need for a timely summarization of the current research status and a clear identification of future research directions in these advanced and evolving technologies. Therefore, Journal of Road Engineering has undertaken the significant initiative of introducing a comprehensive review paper with the overarching theme of “advanced road materials, structures, equipment, and detection technologies”. This extensive and insightful review meticulously gathers and synthesizes research findings from 39 distinguished scholars, all of whom are affiliated with 19 renowned universities or research institutions specializing in the diverse and multidimensional field of highway engineering. It covers the current state and anticipates future development directions in the four major and interconnected domains of road engineering: advanced road materials, advanced road structures and performance evaluation, advanced road construction equipment and technology, and advanced road detection and assessment technologies

Does Neighborhood Social Capital Longitudinally Affect the Nutritional Status of School-Aged Children? Evidence from China

Previous research linking social capital to child nutritional status primarily constitutes cross-sectional studies. To investigate whether a longitudinal relationship exists, by conducting fixed-effects analyses with 16,977 repeatedly measured observations of 6193 children from the 2012, 2014, 2016, and 2018 China Family Panel Studies, this study explored the longitudinal effects of neighborhood participation, bonding trust, and bridging trust on the BMI-for-age z-score (BAZ) and BMI categories of school-aged children, differentiating between urban and rural residence. We found an increasing average BAZ, a decreasing prevalence of underweight, an increasing prevalence of overweight/obesity, and a reducing urban/rural gap in nutritional status. The levels of social capital components descended faster in the urban area. Bonding trust was predictive of a lower BAZ, a higher likelihood of being underweight, and a lower likelihood of being overweight/obese. Bridging trust was predictive of a higher BAZ. The longitudinal effects of bonding trust were significant among only the rural children. Our findings indicate that neighborhood social capital may impose causal impacts on the nutritional status of children. To effectively improve child nutritional status, a more empathetic governmental approach that promotes a more supportive distal social environment is needed

Does social capital aid in leveling the income gradient in child mental health? A structural analysis of the left-behind and not-left-behind Chinese children

Abstract Background Few prior studies have investigated the income gradient in child mental health from a socio-environmental perspective. In an age when child mental health problems in a rapidly changing social environment have become a worldwide issue, an understanding of the socio-environmental mechanisms of the income disparities in child mental health outcomes is imperative and cost-effective. Methods By conducting structural equation analyses with Chinese nationally representative survey data, this study explored the family income gradient in child depression and its potential socio-environmental pathways at the neighborhood, family and school levels, differentiating left-behind and not-left-behind children. Results We found a robust family income gradient in depressive symptoms. Neighborhood cohesion mitigated the income gradient in depressive symptoms by playing a suppression role. School social capital acted as a mediator. Neighborhood trust, neighborhood safety and family social capital played no significant impact. The mitigating and mediating roles of social capital components were significant among only the not-left-behind children. Conclusions To reduce income-related inequalities in child mental health in the long run, integrating policies that directly reduce poverty with policies that improve distal socio-environments is necessary

How Do Students Become Good Workers? Investigating the Impact of Gender and School on the Relationship between Career Decision-Making Self-Efficacy and Career Exploration

In the field of vocational psychology, career decision-making self-efficacy (CDMSE) and career exploration (CE) are considered the crucial factors for developing a sustainable career. This study investigated the relationship between CDMSE and CE among Chinese high-school students, as well as the moderating effects of gender and school. From 2019 to 2021, 24,273 students from 13 different high schools were recruited in the study (male = 15,050, female = 9223; urban schools = 12,327, rural schools = 11,946). The results showed that (i) male students scored significantly higher than female students in both CDMSE and CE, (ii) students from urban schools scored significantly higher than students from rural schools in both CDMSE and CE, (iii) CDMSE positively predicted CE, and (iv) school moderated the relationship between CDMSE and CE, with the effect of CDMSE on CE stronger among rural school students; a moderating effect of gender was not found. These findings indicate that promoting CDMSE can lead high-school students, especially rural school students, to engage more in CE to ensure sustainable career development under the protean and boundaryless career orientation

Effect of orthopedic insoles on lower limb motion kinematics and kinetics in adults with flat foot: a systematic review

Flatfoot is characterized by the collapse of the medial longitudinal arch, eversion of the rearfoot and abduction of the loaded forefoot. Orthopedic insoles are the frequently recommended treatment to support the arch of the foot, adjust the structure of the foot, reduce pain, improve stability and new techniques have been applied to the design of orthopedic insoles in recent years. However, the effectiveness of orthopedic insoles in different motions is still debated from the perspective of biomechanics. Therefore, this study aimed to explore the impact of orthopedic insoles on the kinematics and kinetics of lower limb motion, and to verify effectiveness and propose possible future research directions. We conducted a literature search across three databases employing Boolean operations and filtered results based on eligibility criteria. A total of 671 relevant literature were searched in this review, and 19 literature meeting the requirements were finally included. The results showed that: 1) orthopedic insoles were effective when patients walk, run and jump from the perspective of biomechanics; 2) orthopedic insoles had different result on the change of ankle sagittal angle, moment and peak pressure in the metatarsal region; 3) Whether the effect of insoles, which uses new techniques such as different 3D printed technologies and adds various accessories, can be further improved remains to be further studied; 4) Follow-up studies can pay more attention to the differences between diverse populations, increase the breadth of running and jumping and other movements research and long-term intervention