Background: The novel coronavirus disease 2019 (COVID-19) broke out globally. Early prediction of the clinical progression was essential but still unclear. We aimed to evaluate the timeline of COVID-19 development and analyze risk factors of disease progression. Methods: In this retrospective study, we included 333 patients with laboratory-confirmed COVID-19 infection hospitalized in the Third People's Hospital of Shenzhen from 10 January to 10 February 2020. Epidemiological feature, clinical records, laboratory and radiology manifestations were collected and analyzed. 323 patients with mild-moderate symptoms on admission were observed to determine whether they exacerbated to severe-critically ill conditions (progressive group) or not (stable group). We used logistic regression to identify the risk factors associated with clinical progression. Results: Of all the 333 patients, 70 (21.0%) patients progressed into severe-critically ill conditions during hospitalization and assigned to the progressive group, 253 (76.0%) patients belonged to the stable group, another 10 patients were severe before admission. we found that the clinical features of aged over 40 (3.80 [1.72, 8.52]), males (2.21 [1.20, 4.07]), with comorbidities (1.78 [1.13, 2.81]) certain exposure history (0.38 [0.20, 0.71]), abnormal radiology manifestations (3.56 [1.13, 11.40]), low level of T lymphocytes (0.99 [0.997, 0.999]), high level of NLR (0.99 [0.97, 1.01]), IL-6 (1.05 [1.03, 1.07]) and CRP (1.67 [1.12, 2.47]) were the risk factors of disease progression by logistic regression. Conclusions: The potential risk factors of males, older age, with comorbidities, low T lymphocyte level and high level of NLR, CRP, IL-6 can help to predict clinical progression of COVID-19 at an early stage.

Lipid metabolites are emerging as pivotal regulators of protein function and cell signaling. The availability of intracellular fatty acid is tightly regulated by glycolipid metabolism and may affect human body through many biological mechanisms. Recent studies have demonstrated palmitate, either from exogenous fatty acid uptake or de novo fatty acid synthesis, may serve as the substrate for protein palmitoylation and regulate protein function via palmitoylation. Palmitoylation, the most-studied protein lipidation, encompasses the reversible covalent attachment of palmitate moieties to protein cysteine residues. It controls various cellular physiological processes and alters protein stability, conformation, localization, membrane association and interaction with other effectors. Dysregulation of palmitoylation has been implicated in a plethora of diseases, such as metabolic syndrome, cancers, neurological disorders and infections. Accordingly, it could be one of the molecular mechanisms underlying the impact of palmitate metabolite on cellular homeostasis and human diseases. Herein, we explore the relationship between lipid metabolites and the regulation of protein function through palmitoylation. We review the current progress made on the putative role of palmitate in altering the palmitoylation of key proteins and thus contributing to the pathogenesis of various diseases, among which we focus on metabolic disorders, cancers, inflammation and infections, neurodegenerative diseases. We also highlight the opportunities and new therapeutics to target palmitoylation in disease development.

Background The age‐related decline in testosterone levels is thought to be of great importance for male aging and cardiovascular diseases. However, data are controversial on whether abnormal sex hormones are linked to the presence of cardiovascular diseases and it is also uncertain how blood pressure modifies the association between testosterone levels and major cardiovascular diseases. Methods and Results This is a multicenter, population‐based, cross‐sectional study of 6296 men conducted between 2013 and 2016. Basic information and clinical symptoms were obtained by questionnaires. Blood pressure and plasma levels of total testosterone, sex hormone–binding globulin, luteinizing hormone, and free testosterone were determined in men in a multistage random, cluster sampling in 6 provinces of China. There were 5786 Chinese men (mean [SD] age 55.0 [10.1] years) included after exclusion criteria were applied; 37.2% (2150) of them were diagnosed with hypertension. Total testosterone, free testosterone, and sex hormone–binding globulin were inversely associated with the prevalence of hypertension. Age >65 years or body mass index ≥24 negatively impacted the inverse correlation between testosterone levels and hypertension, whereas smoking and family history of hypertension strengthened the correlation. In participants with grade 2 hypertension, total testosterone was positively associated with the presence of stroke, and luteinizing hormone was also positively correlated with cardiovascular and cerebrovascular diseases. Conclusions Lower total testosterone could be a promising risk marker for prevalent hypertension. Both low and high levels of testosterone are associated with greater cardiovascular risk. Primary hypogonadism may be a risk marker for major cardiovascular diseases in men with severe hypertension.

Abstract Background The novel coronavirus disease 2019(COVID-19) broke out globally. Early prediction of the clinical progression was essential but still unclear. We aimed to evaluate the timeline of COVID-19 development and analyze risk factors of disease progression.Methods In this retrospective study, we included 333 patients with laboratory-confirmed COVID-19 infection hospitalized in the Third People's Hospital of Shenzhen from 10 January to 10 February 2020. Epidemiological feature, clinical records, laboratory and radiology manifestations were collected and analyzed. 323 patients with mild-moderate symptoms on admission were observed to determine whether they exacerbated to severe-critically ill conditions (progressive group) or not (stable group). We used logistic regression to identify the risk factors associated with clinical progression.Results Of all the 333 patients, 70(21.0%) patients progressed into severe-critically ill conditions during hospitalization and assigned to the progressive group, 253(76.0%) patients belonged to the stable group, another 10 patients were severe before admission. we found that the clinical features of aged over 40 (3.80[1.72, 8.52]), males (2.21[1.20, 4.07]), with comorbidities (1.78[1.13, 2.81]) certain exposure history (0.38[0.20, 0.71]), abnormal radiology manifestations (3.56[1.13, 11.40]), low level of T lymphocytes (0.99[0.997, 0.999]), high level of NLR (0.99[0.97, 1.01]), IL-6 (1.05[1.03, 1.07]) and CRP (1.67[1.12, 2.47]) were the risk factors of disease progression by logistic regression.Conclusions the potential risk factors of males, older age, with comorbidities, low T lymphocyte level and high level of NLR, CRP, IL-6 can help to predict clinical progression of COVID-19 at an early stage.

Background Studying human germ cell development and male infertility is heavily relied on mouse models. In vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells (SSCLCs) can be used as a model to study human germ cells and infertility. The current study aimed to develop the SSCLC induction protocol and assess the effects of the developed protocol on SSCLC induction. Methods We examined the effects of valproic acid (VPA), vitamin C (VC) and the combination of VPA and VC on the SSCLC induction efficiency and determined the expression of spermatogonial genes of differentiated cells. Haploid cells and cells expressed meiotic genes were also detected. RNA-seq analysis was performed to compare the transcriptome between cells at 0 and 12 days of differentiation and differently expressed genes were confirmed by RT-qPCR. We further evaluated the alteration in histone marks (H3K9ac and H3K27me3) at 12 days of differentiation. Moreover, the SSCLC induction efficiency of two hiPSC lines of non-obstructive azoospermia (NOA) patients was assessed using different induction protocols. Results The combination of low concentrations of VPA and VC in the induction medium was most effective to induce SSCLCs expressing several spermatogonial genes from human pluripotent stem cells at 12 days of differentiation. The high concentration of VPA was more effective to induce cells expressing meiotic genes and haploid cells. RNA-seq analysis revealed that the induction of SSCLC involved the upregulated genes in Wnt signaling pathway, and cells at 12 days of differentiation showed increased H3K9ac and decreased H3K27me3. Additionally, two hiPSC lines of NOA patients showed low SSCLC induction efficiency and decreased expression of genes in Wnt signaling pathway. Conclusions VPA robustly promoted the differentiation of human pluripotent stem cells into SSCLCs, which involved the upregulated genes in Wnt signaling pathway and epigenetic changes. hiPSCs from NOA patients showed decreased SSCLC induction efficiency and Wnt signaling pathway gene expression, suggesting that SSC depletion in azoospermia testes might be associated with inactivation of Wnt signaling pathway. Our developed SSCLC induction protocol provides a reliable tool and model to study human germ cell development and male infertility.