Although type 2 diabetes (T2D) is a major comorbidity of novel coronavirus disease 2019 (COVID-19), the impact of blood glucose control on the degree of medical interventions required and on all-cause mortality of patients with COVID-19 and pre-existing T2D remains unclear. Here, Zhu et al. report that among $7,300 individuals with COVID-19 (among which nearly 1,000 had T2D) in Hubei Province, China, those with T2D had significantly increased medical interventions and mortality risk. But among the patients with T2D, those with well-controlled blood glucose regulation (upper limit % 10 mmol/L) fared much better than those with poorly controlled blood glucose (upper limit > 10 mmol/L). These findings provide clinical evidence correlating more proper blood glucose control with improved outcomes in patients with COVID-19.

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.

Highlights d Bhlhe40 is required for Trm cell and TIL fitness and function d Bhlhe40 is critical for TIL reinvigoration following anti-PD-L1 blockade d Bhlhe40 programs Trm cell and TIL mitochondrial metabolism and active chromatin state d Epigenetic targeting Trm cell and TIL functional program promotes tumor control

CD8+ tissue-resident memory T (TRM) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8+ TRM maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8+ TRM cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These TRM cells have both exhausted-like phenotypes and memory features and provide heterologous immunity against secondary infection. PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these exhausted-like TRM cells, restoring protective immunity at the cost of promoting postinfection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of exhausted-like TRM cells at the memory phase. Our data indicate that TRM cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.

IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcεR1. In addition to mast cells, many cell types implicated in atherogenesis express FcεR1, but whether IgE has a role in this disease has not been determined. Here, we demonstrate that serum IgE levels are elevated in patients with myocardial infarction or unstable angina pectoris. We found that IgE and the FcεR1 subunit FcεR1α were present in human atherosclerotic lesions and that they localized particularly to macrophagerich areas. In mice, absence of FcεR1α reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcεR1 activity. IgE stimulated the interaction between FcεR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcεR1 or TLR4. Furthermore, IgE activated macrophages by enhancing Na + /H + exchanger 1 (NHE1) activity. Inactivation of NHE1 blocked IgE-induced macrophage production of inflammatory molecules and apoptosis. Cultured human aortic SMCs (HuSMCs) and ECs also exhibited IgE-induced signal transduction, cytokine expression, and apoptosis. In human atherosclerotic lesions, SMCs and ECs colocalized with IgE and TUNEL staining. This study reveals what we believe to be several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases.

The clinical value of MDCT in the preoperative T and N staging of gastric carcinoma is relatively high. MDCT can be the first choice for the preoperative evaluation of patients with gastric carcinoma.

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Non-alcoholic fatty liver disease (NAFLD), ranging from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), is the leading cause of chronic liver diseases. Until now, no medications for NAFLD have been approved by relevant governmental agencies. Dual-specificity phosphatase 9 (Dusp9) is a member of the DUSP protein family. Dusp9 is expressed in insulin-sensitive tissues, and its expression may be modified with the development of insulin resistance (IR). However, the molecular targets and mechanisms of Dusp9 action on NAFLD and NASH remain poorly understood. In this study, by utilizing conditional liver-specific Dusp9-knockout (Dusp9-CKO) mice and Dusp9-transgenic (Dusp9-TG) mice, we showed that Dusp9 was a key suppressor of HFD-induced hepatic steatosis and inflammatory responses and that Dusp9 deficiency aggravated HFHC-induced liver fibrosis. Dusp9 was shown to exert its effects by blocking ASK1 phosphorylation and the subsequent activation of p38 and JNK signaling. In conclusion, hepatocyte Dusp9 prevents NAFL and NASH progression in mice, including lipid accumulation, glucose metabolism disorders, enhanced inflammation and liver fibrosis, in an ASK1-dependent manner. These findings suggest that Dusp9 may be a promising therapeutic target for the treatment of NAFLD and NASH. This article is protected by copyright. All rights reserved.