MDT-28/PLIN-1 mediates lipid droplet-microtubule interaction via DLC-1 in Caenorhabditis elegans

Ectopic lipid accumulation in lipid droplets (LD) has been linked to many metabolic diseases. In this study, DHS-3::GFP was used as a LD marker in C. elegans and a forward genetic screen was carried out to find novel LD regulators. There were 140 mutant alleles identified which were divided into four phenotypic categories: enlarged, aggregated, aggregated and small, and decreased. After genetic mapping, mutations in three known LD regulatory genes (maoc-1, dhs-28, daf-22) and a peroxisome-related gene (acox-3) were found to enlarge LDs, demonstrating the reliability of using DHS-3 as a living marker. In the screen, the cytoskeleton protein C27H5.2 was found to be involved in LD aggregation, as was the LD resident/structure-like protein, MDT-28/PLIN-1. Using yeast two-hybrid screening and pull-down assays, MDT-28/PLIN-1 was found to bind to DLC-1 (dynein light chain). Fluorescence imaging confirmed that MDT-28/PLIN-1 mediated the interaction between DHS-3 labeled LDs and DLC-1 labeled microtubules. Furthermore, MDT-28/PLIN-1 was directly bound to DLC-1 through its amino acids 1-210 and 275-415. Taken together, our results suggest that MDT-28/PLIN-1 is involved in the regulation of LD distribution through its interaction with microtubule-related proteins

Identification of lipid droplet structure-like/resident proteins in Caenorhabditis elegans.

The lipid droplet (LD) is a cellular organelle that stores neutral lipids in cells and has been linked with metabolic disorders. Caenorhabditis elegans has many characteristics which make it an excellent animal model for studying LDs. However, unlike in mammalian cells, no LD structure-like/resident proteins have been identified in C. elegans, which has limited the utility of this model for the study of lipid storage and metabolism. Herein based on three lines of evidence, we identified that MDT-28 and DHS-3 previously identified in C. elegans LD proteome were two LD structure-like/resident proteins. First, MDT-28 and DHS-3 were found to be the two most abundant LD proteins in the worm. Second, the proteins were specifically localized to LDs and we identified the domains responsible for this targeting in both proteins. Third and most importantly, the depletion of MDT-28 induced LD clustering while DHS-3 deletion reduced triacylglycerol content (TAG). We further characterized the proteins finding that MDT-28 was ubiquitously expressed in the intestine, muscle, hypodermis, and embryos, whereas DHS-3 was expressed mainly in intestinal cells. Together, these two LD structure-like/resident proteins provide a basis for future mechanistic studies into the dynamics and functions of LDs in C. elegans

Effect of Ni addition on the preparation of Al2O3–TiB2 composites using high-energy ball milling

Al2O3–TiB2 composites were synthesized using high-energy ball milling from starting powders containing Al, TiO2, and B2O3. To explore the effect of the addition of another ductile metallic phase during milling, 15 wt.% Ni was added to a sample of the starting powders. The phase transformations and microstructure of the milled powder mixtures were investigated using X-ray diffraction and electron microscopy. The results showed that the Ni addition facilitated the mechanochemical reaction between the Al, TiO2, and B2O3. Before the appearance of the Al2O3–TiB2 composite, the intermediate product NiAl was formed by a gradual exothermic reaction. With continued milling, the final phases of Al2O3–TiB2 and Ni were obtained

Association rules analysis on patterns of multimorbidity in adults: based on the National Health and Nutrition Examination Surveys database

Objective To explore the prevalence and patterns of multimorbidity in population with different genders and age ranges.Design A cross-sectional study.Setting National Health and Nutrition Examination Surveys database.Participants 12 576 patients.Primary and secondary outcome measures The prevalence and patterns of multimorbidity.Results High cholesterol had the highest prevalence in all population (33.4 (95% CI: 32.0 to 34.9)) and males. In females <65 years, the most prevalent disease was sleep disorder (32.1 (95% CI: 29.6 to 34.5)) while in females ≥65 years, hypertension was the most prevalent disease (63.9 (95% CI: 59.9 to 67.9)). Hypertension and high cholesterol were associated with the highest support (occur together most frequently) in all population regardless of genders. Hypertension displayed the highest betweenness centrality (mediating role in the network) followed by high cholesterol and arthritis in all population. For males aged <65 years, hypertension and high cholesterol presented the highest betweenness centrality. In males ≥65 years, hypertension, high cholesterol and arthritis were the top three diseases of degree centrality (direct association with other conditions). As for females ≥65 years, hypertension showed the highest betweenness centrality followed by high cholesterol and arthritis. The associations of hypertension, arthritis and one other item with high cholesterol presented the highest support in all population. In males, the associations of depression, hypertension with sleep disorders had the highest lift (the chance of co-occurrence of the conditions and significant association). Among females, the associations of depression, arthritis with sleep disorders had the highest lift.Conclusion Hypertension and high cholesterol were prevalent in all population, regardless of females and males. Hypertension and high cholesterol, arthritis and hypertension, and diabetes and hypertension were more likely to coexist. The findings of this study might help make plans for the management and primary care of people with one or more diseases

The relationship between the sources of confidence in overcoming COVID-19 and the improvement of medical students' professional identity: mediation by medical students' attention to COVID-19

Abstract Background The prevalence of COVID-19 highlights the shortage of human medical resources, and improving medical students' professional identity is crucial to improving this situation. The sources of confidence in overcoming COVID-19 and medical students' attention to COVID-19 were significant factors affecting their professional identity. However, no study has investigated the mediating role of medical students' attention to COVID-19 in their relationship. This study investigates the relationship between these three factors in three medical university students in Hunan Province. Methods A cross-sectional survey study that used convenience sampling method was conducted on 2775 medical students from three universities in the Hunan Province of China from March 15 to April 19, 2020. An intermediary model was established to evaluate the role of medical students' attention to COVID-19 in the sources of confidence in overcoming COVID-19 and the improvement of medical students' professional identity. Results The sources of confidence in overcoming COVID-19, medical students' attention to national crisis events, and the improvement of medical students' professional identity was positively associated with each other (β = 0.328 ~ 0.464, P < 0.001). The mediating effect accounted for 23.3% of the total effect and 30.4% of the direct effect. Medical students' attention to COVID-19 partially mediates the relationship between the sources of confidence to overcome COVID-19 and the improvement of medical students' professional identity. Conclusions This study found that the sources of confidence in overcoming COVID-19 and medical students' attention to national crisis events have a significant predictive effect on the improvement of medical students' professional identity. Medical students' attention to COVID-19 mediated the relationship between the sources of confidence to overcome COVID-19 and the improvement of medical students' professional identity. The findings have emphasized the theoretical and practical significance of professional identity education for medical students

CD30 Is Highly Expressed in Chronic Obstructive Pulmonary Disease and Induces the Pulmonary Vascular Remodeling

Chronic obstructive pulmonary disease (COPD) is one of the common and underdiagnosed diseases with the highest morbidity and mortality in the world. The development of COPD can lead to pulmonary vascular remodeling and pulmonary hypertension, further causing the occurrence of pulmonary heart disease. Therefore, attenuation of pulmonary vascular remodeling and pulmonary hypertension caused by COPD can significantly delay cardiovascular complications. In the study, we firstly found that the expression of CD30 and CD30L was increased in COPD. Importantly, the serum CD30L levels were significantly higher in patients with stable COPD relative to those with acute exacerbation of COPD (AECOPD). This suggested that CD30 might be related to the development of COPD. In addition, we found that the expression of CD30 in the COPD rat model was significantly increased compared with control group. And treatment with the anti-CD30 antibody reduced the serum concentration and tissue expression of CD30 in rat. Importantly, anti-CD30 antibody alleviated pulmonary vascular remodeling in COPD model rats. This suggested that CD30 played an important role in the course of COPD. Finally, we found that, in the HPASMC and HPAEC cell lines, CD30 can affect the cell viability and cell migration and inhibited hypoxia-induced cell apoptosis in a concentration-dependent manner. We also found CD30 induced extracellular matrix formation through decreasing the expression of MMP-2, thus promoting the pulmonary vascular remodeling. The study indicated that CD30 and CD30L were involved in pulmonary vascular remodeling and inflammatory response in COPD. Altogether, CD30 might be a marker for the early diagnosis and progression of COPD