C. elegans fatty acid two-hydroxylase regulates intestinal homeostasis by affecting heptadecenoic acid production

Background/Aims: The hydroxylation of fatty acids at the C-2 position is the first step of fatty acid α-oxidation and generates sphingolipids containing 2-hydroxy fatty acyl moieties. Fatty acid 2-hydroxylation is catalyzed by Fatty acid 2-hydroxylase (FA2H) enzyme. However, the precise roles of FA2H and fatty acid 2-hydroxylation in whole cell homeostasis still remain unclear. Methods: Here we utilize Caenorhabditis elegans as the model and systemically investigate the physiological functions of FATH-1/C25A1.5, the highly conserved worm homolog for mammalian FA2H enzyme. Immunostaining, dye-staining and translational fusion reporters were used to visualize FATH-1 protein and a variety of subcellular structures. The “click chemistry” method was employed to label 2-OH fatty acid in vivo. Global and tissue-specific RNAi knockdown experiments were performed to inactivate FATH-1 function. Lipid analysis of the fath-1 deficient mutants was achieved by mass spectrometry. Results: C. elegans FATH-1 is expressed at most developmental stages and in most tissues. Loss of fath-1 expression results in severe growth retardation and shortened lifespan. FATH-1 function is crucially required in the intestine but not the epidermis with stereospecificity. The “click chemistry” labeling technique showed that the FATH-1 metabolites are mainly enriched in membrane structures preferable to the apical side of the intestinal cells. At the subcellular level, we found that loss of fath-1 expression inhibits lipid droplets formation, as well as selectively disrupts peroxisomes and apical endosomes. Lipid analysis of the fath-1 deficient animals revealed a significant reduction in the content of heptadecenoic acid, while other major FAs remain unaffected. Feeding of exogenous heptadecenoic acid (C17: 1), but not oleic acid (C18: 1), rescues the global and subcellular defects of fath-1 knockdown worms. Conclusion: Our study revealed that FATH-1 and its catalytic products are highly specific in the context of chirality, C-chain length, spatial distribution, as well as the types of cellular organelles they affect. Such an unexpected degree of specificity for the synthesis and functions of hydroxylated FAs helps to regulate protein transport and fat metabolism, therefore maintaining the cellular homeostasis of the intestinal cells. These findings may help our understanding of FA2H functions across species, and offer potential therapeutical targets for treating FA2H-related diseases

The Role of Social Support and Environment: The Mediating Effect of College Students’ Psychology and Behavior

Purpose: explore the interaction mechanism among college students’ social support, environment, behavior and psychology, so as to provide reference for college students’ behavior guidance and mental health intervention. Methods: 2,510 college students were investigated by general situation questionnaire and college students' quality of life evaluation concise scale (QOLCS-23). Result: (1) social support has a significant positive correlation with environment, behavior and psychology; (2) behavior plays a partial mediating role between social support, environment and college students’ psychology. The mediating effect is significant, and the proportion of mediating effect is 55.22%; (3) compared with life behavior, time management contributes more to college students’ behavior ( β = 0.75, P < 0.001). Conclusion: social support and environment can directly predict the psychology of college students, and can also indirectly affect their psychology through behavior. To improve college students’ mental health level, we should pay attention to college students’ feelings and satisfaction of social support and environment, guide college students to build good behavior, especially establish the awareness of time management

Follistatin N terminus differentially regulates muscle size and fat in vivo

Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV). Overexpression of wild-type FST in normal mice greatly increased muscle mass while decreasing fat accumulation, whereas overexpression of an N terminus mutant or N terminus-deleted FST had no effect on muscle mass but moderately decreased fat mass. In contrast, FST-I-I containing the complete N terminus and double domain I without domain II and III had no effect on fat but increased skeletal muscle mass. The effects of different constructs on differentiated C2C12 myotubes were consistent with the in vivo finding. We hypothesized that ND was critical for myostatin blockade, mediating the increase in muscle mass, and was less pivotal for activin binding, which accounts for the decrease in the fat tissue. An in vitro TGF-beta1-responsive reporter assay revealed that FST-I-I and N terminus-mutated or -deleted FST showed differential responses to blockade of activin and myostatin. Our study provided direct in vivo evidence for a role of the ND of FST, shedding light on future potential molecular designs for FST-based gene therapy

Flexible and high-performance piezoresistive strain sensors based on carbon nanoparticles@polyurethane sponges

In this work, flexible and high-performance piezoresistive strain sensors were fabricated by simple layer-by-layer electrostatic self-assembly of carbon nanoparticles on commercial polyurethane (PU) sponges. It was shown that the sponge-based strain sensors exhibited obviously positive and negative piezoresistive characteristics under tensile and compressive strains, respectively. The alternate assembly of carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs) contributed to the construction of a more complete conductive network and significantly improved the sensing performance of the sensor due to the synergistic effect between CNTs and GNPs. Compared with the CNT@PU and CNT/GNP@PU sponge strain sensors, the CNT/GNP/CNT@PU sensor had a larger strain detection range and higher linearity. Besides, the CNT/GNP/CNT@PU sponge strain sensor showed high sensitivity (GF = 43,000 at 60% tensile strain and GF = −1.1 at 50% compressive strain), responsive capability to very small strain (0.05%) and outstanding stability during 3000 loading cycles. Due to its excellent sensing performance, the CNT/GNP/CNT@PU sensor enabled monitoring of various physiological activities, including finger movements, wrist bending and walking etc. In addition, a 5 × 5 sensor array based on the sponge-based strain sensor was prepared to achieve accurate identification of weight distribution. This study provides valuable information for the development of flexible strain sensors with high-performance and low-cost

Development of Research and Innovation Capacity Index of HEIs on Disaster Resilience Related Studies

Research capacity development is one of the most critical challenges facing HEIs in the Asian countries. Growing the number and quality of researchers is a strategic issue. For academia, developing research capacity can help enhance academic fulfilment as well as provide career advancement. The notion that excellent people are a resource to be treasured has led to increased attention being paid to how to attract, support and retain them, thereby building research capacity. This paper is part of an Erasmus plus co-funded project called ASCENT, which focuses on building the research and innovation capacity (R&I) of Higher Education Institutions (HEI) on disaster resilience related studies. This paper particularly aims at reviewing the current context and gaps in the literature with regards to the indices used to assess the research capacity of the higher education institutions. Qualitative systematic review approach was adopted at the initial stage, followed by three-round Focus Group Discussion with high -level academics from 14 countries in Asia and Europe. Twenty-one Key Performance Indicators (KPIs) of HEIs Research and Innovation Capacity were identified, which were grouped into three themes: Structure, System, and Policy; Skills and Training; and Staff

Association Analysis of NLRP3 Inflammation-Related Gene Promotor Methylation as Well as Mediating Effects on T2DM and Vascular Complications in a Southern Han Chinese Population

Objective: To explore the association between the methylation levels in the promoter regions of the NLRP3, AIM2, and ASC genes and T2DM and its vascular complications in a Southern Han Chinese population and further analyze their interaction and mediating effects with environmental factors in T2DM.Methods: A case-control study was used to determine the association between population characteristics, the methylation level in the promoter region of the NLRP3, AIM2, and ASC genes and T2DM and vascular complications. A mediating effect among genes-environment-T2DM and the interaction of gene-gene or gene-environment factors was explored.Results: In the logistic regression model with adjusted covariants, healthy people with lower total methylation levels in the AIM2 promoter region exhibited a 2.29-fold [OR: 2.29 (1.28~6.66), P = 0.011] increased risk of developing T2DM compared with higher-methylation individuals. T2DM patients without any vascular complications who had lower methylation levels (&lt;methylation median) in NLRP3 CpG2 and AIM2 total methylation had 6.45 (OR: 6.45, 95% CI: 1.05~39.78, P = 0.011) and 9.48 (OR: 9.48, 95% CI: 1.14~79.00, P = 0.038) times higher risks, respectively, of developing diabetic microvascular complications than T2DM patients with higher methylation. Similar associations were also found between the lower total methylation of the NLRP3 and AIM2 promoter regions and macrovascular complication risk (NLRP3 OR: 36.03, 95% CI: 3.11~417.06, P = 0.004; AIM2 OR: 30.90, 95% CI: 2.59~368.49, P = 0.007). Lower NLRP3 promoter total methylation was related to a 17.78-fold increased risk of micro-macrovascular complications (OR: 17.78, 95% CI: 2.04~155.28, P = 0.009). Lower ASC CpG1 or CpG3 methylation levels had significant partial mediating effects on T2DM vascular complications caused by higher age (ASC CpG1 explained approximately 52.8% or 32.9% of the mediating effect of age on macrovascular or macro-microvascular complications; ASC CpG3 explained approximately 38.9% of the mediating effect of age on macrovascular complications). No gene-gene or gene-environment interaction was identified in T2DM.Conclusion: Lower levels of AIM2 promoter total methylation might increase the risk of T2DM. NLRP3, AIM2, and ASC promoter total methylation or some CpG methylation loss might increase the risk of T2DM vascular complications, which merits further study to support the robustness of these findings