Proteomic analysis reveals proteins and pathways associated with declined testosterone production in male obese mice after chronic high-altitude exposure

ObjectiveObesity is common in highland areas owing to lifestyle alterations. There are pieces of evidence to suggest that both obesity and hypoxia may promote oxidative stress, leading to hypogonadism in males. These findings indicate an increased risk of hypogonadism in obese males following hypoxia exposure. However, the mechanisms underlying the disease process remain unclear. The current study aims to explore the mechanism of testosterone production dysfunction in obese male mice exposed to a chronic high-altitude hypoxia environment.MethodsAn obese male mouse model was generated by inducing obesity in mice via a high-fat diet for 14 weeks, and the obese mice were then exposed to a high-altitude hypoxia environment for 24 days. Sera and testicular tissues were collected to detect serum lipids, sex hormone level, and testicular oxidative stress indicators. Morphological examination was performed to assess pathological alterations in testicular tissues and suborganelles in leydig cells. Proteomic alterations in testicular tissues were investigated using quantitative proteomics in Obese/Control and Obese-Hypoxia/Obese groups.ResultsThe results showed that chronic high-altitude hypoxia exposure aggravated low testosterone production in obese male mice accompanied by increased testicular oxidative stress and histological damages. In total, 363 and 242 differentially expressed proteins (DEPs) were identified in the two comparison groups, Obese/Control and Obese-Hypoxia/Obese, respectively. Functional enrichment analysis demonstrated that several significant functional terms and pathways related to testosterone production were altered in the two comparison groups. These included cholesterol metabolism, steroid hormone biosynthesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, oxidative stress responses, as well as retinol metabolism. Finally, 10 representative DEPs were selected for parallel reaction monitoring verification. Among them, StAR, DHCR7, NSDHL, CYP51A1, FDPS, FDX1, CYP11A1, ALDH1A1, and GPX3 were confirmed to be downregulated in the two groups.ConclusionsChronic hypoxia exposure could exacerbate low testosterone production in obese male mice by influencing the expression of key proteins involved in steroid hormone biosynthesis, cholesterol biosynthesis, oxidative stress responses and retinol metabolism

Minimizing the Spread of Negative Influence in SNIR Model by Contact Blocking

This paper presents a method to minimize the spread of negative influence on social networks by contact blocking. First, based on the infection-spreading process of COVID-19, the traditional susceptible, infectious, and recovered (SIR) propagation model is extended to the susceptible, non-symptomatic, infectious, and recovered (SNIR) model. Based on this model, we present a method to estimate the number of individuals infected by a virus at any given time. By calculating the reduction in the number of infected individuals after blocking contacts, the method selects the set of contacts to be blocked that can maximally reduce the affected range. The selection of contacts to be blocked is repeated until the number of isolated contacts that need to be blocked is reached or all infection sources are blocked. The experimental results on three real datasets and three synthetic datasets show that the algorithm obtains contact blockings that can achieve a larger reduction in the range of infection than other similar algorithms. This shows that the presented SNIR propagation model can more precisely reflect the diffusion and infection process of viruses in social networks, and can efficiently block virus infections

Hepatitis C screening in hospitals: find the missing patients

Abstract Background Hepatitis C virus (HCV) infection is one of the leading causes of liver cancer, creating enormous economic and social burdens. The Chinese government recommends routine screening of inpatients for HCV before invasive procedures to prevent iatric infections. However, the diagnosis and treatment rates for HCV remain low. The aim of this study was to use available routine screening data to understand the HCV screening of inpatients in different regions of China. Methods Inpatient information and HCV screening results were collected from January 2016 to December 2016 at eight tertiary hospitals in different regions of China to compare the HCV-positivity of hospitalized patients among different regions and age groups. Results The HCV screening rate of inpatients was more than 50%. A total of 467,008 inpatients were enrolled in the study (51.20% were male), and the HCV antibody (anti-HCV) -positive rate was 0.88% (95% confidence interval [CI], 0.85–0.91%) among the total population. This rate was significantly higher among all males compared with all females (0.91% vs 0.85%). Moreover, the HCV antibody-positive rate increased with age and was highest for the 60–64-year age group. Notably, 90.14% (3722/4129) of the anti-HCV seropositive patients were 40 years of age or older. HCV screening for people over 40 years old is recommended. Conclusions This study highlights the key role of routine examination for HCV infection in hospitalized patients. Full use of inpatient screening results to manage HCV antibody-positive patients and a screening strategy targeting inpatients 40 years and older were found to be low-cost and effective, which will help to find the missing millions of yet unaware patients and also accelerate the elimination of HCV in China

Natural variation in the HAN1 gene confers chilling tolerance in rice and allowed adaptation to a temperate climate

Rice (Oryza sativa L.) is a chilling-sensitive staple crop that originated in subtropical regions of Asia. Introduction of the chilling tolerance trait enables the expansion of rice cultivation to temperate regions. Here we report the cloning and characterization of HAN1, a quantitative trait locus (QTL) that confers chilling tolerance on temperate japonica rice. HAN1 encodes an oxidase that catalyzes the conversion of biologically active jasmonoyl-L-isoleucine (JA-Ile) to the inactive form 12-hydroxy-JA-Ile (12OH-JA-Ile) and fine-tunes the JA-mediated chilling response. Natural variants in HAN1 diverged between indica and japonica rice during domestication. A specific allele from temperate japonica rice, which gained a putative MYB cis-element in the promoter of HAN1 during the divergence of the two japonica ecotypes, enhances the chilling tolerance of temperate japonica rice and allows it to adapt to a temperate climate. The results of this study extend our understanding of the northward expansion of rice cultivation and provide a target gene for the improvement of chilling tolerance in rice