ChREBP-Mediated Choline Deprivation and Chemokine Secretion Shape Tumor-Associated Macrophages to Promote Immune Evasion.

Tumor metabolic reprogramming has been recognized as a critical determinant in tumor development and cancer immunotherapy response. Aberrant choline metabolism is emerging as a defining hallmark of cancer. Here, we found that carbohydrate responsive element binding protein (ChREBP)-mediated choline deprivation induced tumor-associated macrophage (TAM) reprogramming and maintained an immunosuppressive tumor microenvironment (TME).

Compromised efferocytosis during aging is related to COVID-19 severity in mice.

Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019 (COVID-19). In older individuals, a dysregulated immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contributes to disease severity; however, the underlying mechanism remains elusive. In this study, we established an aging mouse model of COVID-19, successfully replicating the development of a relatively severe disease in older adults.

Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model.

The elderly population, who have increased susceptibility to severe outcomes, have been particularly impacted by the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to a global health crisis. However, definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain unclear. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19.

Establishment of a novel minigenome system for the identification of drugs targeting Nipah virus replication.

Nipah virus (NiV) is a deadly zoonotic pathogen with high potential to cause another pandemic. Owing to biosafety concerns, studies on living NiV must be performed in biosafety level 4 (BSL-4) laboratories, which greatly hinders the development of anti-NiV drugs. To overcome this issue, minigenome systems have been developed to study viral replication and screen for antiviral drugs.

Mutual antagonism of mouse-adaptation mutations in HA and PA proteins on H9N2 virus replication.

Avian H9N2 viruses have wide host range among the influenza A viruses. However, knowledge of H9N2 mammalian adaptation is limited. To explore the molecular basis of the adaptation to mammals, we performed serial lung passaging of the H9N2 strain A/chicken/Hunan/8.

A novel mAb broadly neutralizes SARS-CoV-2 VOCs in vitro and in vivo, including the Omicron variants.

Novel immune escape variants have emerged as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor-binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS-CoV-2 variants of concern (VOCs) in vitro and in vivo.

High-Intensity Ultraviolet-C Irradiation Efficiently Inactivates SARS-CoV-2 Under Typical Cold Chain Temperature.

SARS-CoV-2 contaminated items in the cold chain becomes a threat to public health, therefore the effective and safe sterilization method fit for the low temperature is needed. Ultraviolet is an effective sterilization method while its effect on SARS-CoV-2 under low-temperature environment is unclear. In this research, the sterilization effect of high-intensity ultraviolet-C (HIUVC) irradiation against SARS-CoV-2 and Staphylococcus aureus on different carriers at 4 °C and - 20 °C was investigated.

m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine.

Background: The RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification.

Highly Pathogenic Avian Influenza A (H5N1) Virus in Swans, Central China, 2021.

Six highly pathogenic avian influenza (HPAI) H5N1 viruses (clade 2.3.4.

Genetic and Pathogenic Characterization of Avian Influenza Virus in Migratory Birds between 2015 and 2019 in Central China.

Active surveillance of avian influenza virus (AIV) in wetlands and lakes is important for exploring the gene pool in wild birds. Through active surveillance from 2015 through 2019, 10,900 samples from wild birds in central China were collected, and 89 AIVs were isolated, including 2 subtypes of highly pathogenic AIV and 12 of low-pathogenic AIV; H9N2 and H6Ny were the dominant subtypes. Phylogenetic analysis of the isolates demonstrated that extensive intersubtype reassortments and frequent intercontinental gene exchange occurred in AIVs.

Sperm-Associated Antigen 9 Promotes Influenza A Virus-Induced Cell Death via the c-Jun N-Terminal Kinase Signaling Pathway.

Upon influenza A virus (IAV) infection, the IAV progeny ribonucleoprotein complex, with a defective viral genome, is sensed by DNA-dependent activator of interferon-regulatory factor (DAI). DAI initiates the recruitment of an array of proteins to form a multiprotein platform (PANoptosome), which triggers apoptosis, necroptosis, and pyroptosis during IAV infection. However, the mechanisms mediating the assembly of the PANoptosome are unclear.

G Protein Subunit β1 Facilitates Influenza A Virus Replication by Promoting the Nuclear Import of PB2.

G protein subunit β1 (GNB1), the beta subunit of the G protein family, plays an important role in regulating transmembrane signal transduction. Although a recent study has demonstrated that GNB1 can bind the matrix protein 1 (M1) to facilitate M1 transport to budding sites and promote the release of progeny influenza A virus (IAV), whether the GNB1 protein has other functions in IAV replication requires further study. Here, we found that GNB1 promoted IAV replication, as virus yield decreased in GNB1 knockdown or knockout cells.

Development of a biosensor assessing SARS-CoV-2 main protease proteolytic activity in living cells for antiviral drugs screening.

• The biosensor reported in our study can monitor SARS-CoV-2 M activity in living cells instead of solutions. • The biosensor reported in our study is sensitive and easy to operate. • It is suitable for high-throughput screening.

Circulation, genomic characteristics, and evolutionary dynamics of class I Newcastle disease virus in China.

Newcastle disease caused by Newcastle disease virus (NDV) is one of the most serious threats to chickens and has two clinical forms, typical and atypical, caused by velogenic and lentogenic strains, respectively. To control the epidemic, many vaccines against velogenic class II NDVs have been introduced worldwide, but this has led to accelerated mutation of class II viruses under immune pressure and, on the other hand, to non-vaccine targeting class I NDVs becoming the dominant population in poultry. In this context, this study provided the first large-scale genomic epidemiological and quasispecies dynamic analysis of class I NDVs in China, and found that class I viruses that first appeared in East and South China have spread to central China and become the dominant class with an average evolutionary rate of 1.

Molecular Events Involved in Influenza A Virus-Induced Cell Death.

Viral infection usually leads to cell death. Moderate cell death is a protective innate immune response. By contrast, excessive, uncontrolled cell death causes tissue destruction, cytokine storm, or even host death.

LIGHT of pulmonary NKT cells annihilates tissue protective alveolar macrophages in augmenting severe influenza pneumonia.

CD1d-restricted natural killer T (NKT) cells are innate-like T lymphocytes with protective or pathogenic roles in the development of influenza pneumonia. Here, we show that lung-infiltrated and activated NKT cells are the major cellular source of LIGHT/TNFSF14, which determines the severity of pulmonary pneumonia by highly deteriorative influenza A virus (IAV) infection. Compared to wild-type mice, LIGHT mice exhibit much lower morbidity and mortality to IAV, due to alleviated lung damage and reduced apoptosis of alveolar macrophages (AMs).

miR-128 participates in the pathogenesis of chronic constipation by regulating the p38α/M-CSF inflammatory signaling pathway.

Chronic constipation (CC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in CC.

Emerging highly pathogenic avian influenza (H5N8) virus in migratory birds in Central China, 2020.

Eleven highly pathogenic avian influenza H5N8 viruses (clade 2.3.4.

Statistical Binding Matching between Influenza A Virus and Dynamic Glycan Clusters Determines Its Adhesion onto Lipid Membranes.

The resistance of drugs to the new influenza A virus (IAV) strains and the limited efficiency of vaccines to prevent seasonal flu epidemics underscore the urgency in finding novel strategies to block IAV infection, which is required to gain insights into the mechanism of the initial step of IAV adhesion. While it is well established that IAVs bind to respiratory tract cells by recognizing sialylated glycans on host cell membranes through a multivalency effect, how IAVs dynamically respond to multiple glycan receptors distinct valencies has not been fully understood, limiting the discovery of novel anti-flu strategies. Using single-particle tracking to record the 2D mobilities and surface residence times of highly pathogenic H5N1 avian IAVs adhered to fluidic membranes containing α2-3 sialylated GM3 glycolipids, we quantified the univalent and multivalent IAV adhesion channels, which provide insights into the mechanism of IAV binding; IAV can guide the clustering of dynamic glycolipids to statistically match the multivalent binding affinities for IAV adhesion.