The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.

Objective: The purpose of this study was to investigate the effects of Tai Chi (TC) on arterial stiffness, physical function of lower-limb, and cognitive ability in adults aged over 60. Methods: This study was a prospective and randomized 12-week intervention trial with three repeated measurements (baseline, 6, and 12 weeks). Sixty healthy adults who met the inclusion criteria were randomly allocated into three training conditions (TC-24, TC-42, and TC-56) matched by gender, with 20 participants (10 males, 10 females) in each of the three groups. We measured the following health outcomes, including markers of atherosclerosis, physical function (leg power, and static and dynamic balance) of lower-limb, and cognitive ability. Results: When all three TC groups (p < 0.05) have showed significant improvements on these outcomes but overall cognitive ability at 6 or 12 weeks training period, TC-56 appears to have superior effects on arterial stiffness and static/dynamic balance in the present study. Conclusions: Study results of the present study add to growing body of evidence regarding therapeutic TC for health promotion and disease prevention in aging population. Future studies should further determine whether TC-42 and TC-56 are beneficial for other non-Chinese populations, with rigorous research design and follow-up assessment.

New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in de novo pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.

Introduction. Sex hormones play an important role in the development and maintenance of bone and muscle mass. However, studies regarding serum testosterone levels, osteoporosis, and sarcopenia in men are relatively sparse and have led to contradictory conclusions. Therefore, this study aimed to investigate the association between serum testosterone levels and body composition, including bone mineral density (BMD), appendicular lean mass index (ALMI), and appendicular fat mass index (AFMI), among men 20–59 years of age through a cross-sectional analysis of the National Health and Nutrition Examination Survey. Materials and Methods. Our analysis was based on the data for 3,875 men, 20–59 years of age. Weighted multiple regression analyses were used to estimate the independent association between serum testosterone levels and body composition. Weighted generalized additive models and smooth curve fittings were used to characterize the nonlinear associations between them. Results. The association between the serum testosterone level and lumbar BMD was positive in each multivariable linear regression model. In the model adjusted for age and race, the serum testosterone level was negatively associated with ALMI. However, in the models adjusted for body mass index, this association became positive. In addition, the association between the serum testosterone level and AFMI was negative in each multivariable linear regression model. Conclusion. Our study demonstrated a positive association of serum testosterone level with lumbar BMD and ALMI, and a negative association with AFMI, among men 20–59 years of age, suggesting that increasing testosterone levels may be beneficial to skeletal health in young and middle-aged men with low testosterone levels.

The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic may raise a potentially severe threat to public health. However, little is known about the consequences of the co-infection of influenza A virus (IAV) and SARS-CoV-2. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Intriguingly, such enhancement of SARS-CoV-2 infectivity was only seen under co-infection with IAV but not with several other viruses including Sendai virus, human rhinovirus, human parainfluenza virus, human respiratory syncytial virus, or human enterovirus 71. IAV infection rather than interferon signaling induced elevated expression of ACE2 essential for such enhancement of SARS-CoV-2 infectivity. Remarkably, we further confirmed that the pre-infection of IAV indeed resulted in an increased SARS-CoV-2 viral load and more severe lung damage in hACE2-transgenic mice. This study illustrates that the co-infection of IAV aggravates SARS-CoV-2 infection and disease severity, which in turn suggests that preventing the convergence of flu season and COVID-19 pandemic would be of great significance.

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Background Osteosarcoma (OS) is the most common and malignant bone tumor among children and adolescents worldwide. Over decades, clinical treatment for osteosarcoma has proven to be intractable. Novel approaches, such as immunotherapy, face immune escape. Thus, exploring potential therapeutic targets for osteosarcoma is an urgent need. Method Gene expression data and clinical information were downloaded from Therapeutically Applicable Research to Generate Effective Treatments (TARGET), Gene Expression Omnibus (GEO), and Univariate Cox regression analysis was used to identify prognostic necroptosis-related genes (NRGs). A non-negative matrix factorization algorithm (NMF) was used to cluster patients into various molecular subgroups with NRGs. We dealt with multi-collinearity with the least absolute shrinkage and selection operator (LASSO). Multivariate Cox regression was used to construct the prediction model that divided OS patients into two risk groups. The model's validity was assessed by time-dependent receiver operating characteristic (ROC) analysis. Different expression genes (DEGs) between these two groups were conducted for functional analysis, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA). Eight algorithms were carried out to evaluate the tumor microenvironment. These marker genes on the single-cell transcriptome were further labeled to explore whether their expression was cell-specific. Results Based on the model constructed by 5 NRGs (TLR4, STAT5A, IFNGR1, PYGM, CHMP4C), the patients were divided into two risk groups. Patients in the high-risk group suffered a poorer prognosis than those in the low-risk group. The nomogram was constructed and integrated with clinical features and gene signatures, demonstrating better predictive ability in training and testing cohorts. Immune cell infiltrations were highly associated with the risk score generated by Multivariate Cox. All 5 NRGs can be successfully marked on the feature plot of single-cell RNA-Seq, and two NRGs were associated with cell-specific genes of osteosarcoma pluripotency with statistical significance. Conclusion This study can provide a reference for diagnosing molecular subtyping and treating patients with OS.

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