Unidirectional Regulation of Vimentin Intermediate Filaments to Caveolin-1.

Both the mechanosensitive vimentin cytoskeleton and endocytic caveolae contribute to various active processes such as cell migration, morphogenesis, and stress response. However, the crosstalk between these two systems has remained elusive. Here, we find that the subcellular expression between vimentin and caveolin-1 is mutual exclusive, and vimentin filaments physically arrest the cytoplasmic motility of caveolin-1 vesicles.

TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8 T-cell numbers.

The host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a role for the DNA demethylase and tumor suppressor TET2 in host anti-tumor immunity. Deletion of Tet2 in mice elevates IL-6 levels upon tumor challenge.

Comparative Antiviral Efficacy of Viral Protease Inhibitors against the Novel SARS-CoV-2 In Vitro.

The recent outbreak of novel coronavirus pneumonia (COVID-19) caused by a new coronavirus has posed a great threat to public health. Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients. Virus-encoded proteases are considered potential drug targets.

MAVS Is a Dual Target during Hepatitis C Virus Infection for Innate Immune Evasion and Viral Replication via NF-κB.

Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew () is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown.

Vagal-α7nAChR signaling attenuates allergic asthma responses and facilitates asthma tolerance by regulating inflammatory group 2 innate lymphoid cells.

Disorders of immune tolerance may lead to allergic asthma. Group 2 innate lymphoid cells (ILC2s) and inflammatory ILC2s (iILC2s) are key players in asthma. The vagus nerve innervating the airways releases acetylcholine or neuropeptides (i.

Ubiquitin-Conjugating Enzyme 2S Enhances Viral Replication by Inhibiting Type I IFN Production through Recruiting USP15 to Deubiquitinate TBK1.

Type I interferon (IFN) plays an essential role in the host innate immune responses. Several ubiquitin-conjugating enzyme (E2) family members were reported to regulate type I IFN production and host antiviral immune responses. However, the molecular mechanisms are still not fully understood.

Regulatory B Lymphocytes Colonize the Respiratory Tract of Neonatal Mice and Modulate Immune Responses of Alveolar Macrophages to RSV Infection in IL-10-Dependant Manner.

Respiratory syncytial virus (RSV) is the prevalent pathogen of lower respiratory tract infections in children. The presence of neonatal regulatory B lymphocytes (nBreg) has been associated with a poor control of RSV infection in human newborns and with bronchiolitis severity. So far, little is known about how nBreg may contribute to neonatal immunopathology to RSV.

iNKT cells with high PLZF expression are recruited into the lung via CCL21-CCR7 signaling to facilitate the development of asthma tolerance in mice.

Establishment of immune tolerance is crucial to protect humans against asthma. Promyelocytic leukemia zinc finger (PLZF) is an emerging suppressor of inflammatory responses. CCL21-CCR7 signaling mediates tolerance development.

The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming.

Evolutionarily conserved SCAN (named after SRE-ZBP, CTfin51, AW-1, and Number 18 cDNA)-domain-containing zinc finger transcription factors (ZSCAN) have been found in both mouse and human genomes. Zscan4 is transiently expressed during zygotic genome activation (ZGA) in preimplantation embryos and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control.

MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6.

Background: The human myxovirus resistance 2 (Mx2/MxB) protein was originally found to regulate cytoplasmic-nuclear transport but was recently reported to restrict HIV-1 replication by binding to HIV-1 capsid (CA), preventing uncoating, the nuclear import of pre-integration complex (PIC) and viral DNA integration. This work explores the mechanisms of MxB-mediated HIV-1 inhibition.

Results: We demonstrated that MxB represses NUP358-mediated PIC nuclear import and HIV-1 replication.

Molecular simulation of SARS-CoV-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection.

We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol).

The distribution of immune cells within combined hepatocellular carcinoma and cholangiocarcinoma predicts clinical outcome.

Background: This study aimed to investigate the clinical relevance of the immune microenvironment in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-ICC).

Patients And Methods: The density of tumor-infiltrating CD3 , CD8 , CD163 , and Foxp3 immune cells, as well as Programmed cell death 1, Programmed cell death-ligand 1, and Tumor necrosis factor receptor superfamily member 4, was measured in the peritumor liver, tumor invasive margin, and intratumor subregions of 56 cHCC-ICC by immunohistochemistry. The immune index was established to stratify patients.

Bi-allelic Missense Pathogenic Variants in TRIP13 Cause Female Infertility Characterized by Oocyte Maturation Arrest.

Normal oocyte meiosis is a prerequisite for successful human reproduction, and abnormalities in the process will result in infertility. In 2016, we identified mutations in TUBB8 as responsible for human oocyte meiotic arrest. However, the underlying genetic factors for most affected individuals remain unknown.

Interfering with retrotransposition by two types of CRISPR effectors: Cas12a and Cas13a.

CRISPRs are a promising tool being explored in combating exogenous retroviral pathogens and in disabling endogenous retroviruses for organ transplantation. The Cas12a and Cas13a systems offer novel mechanisms of CRISPR actions that have not been evaluated for retrovirus interference. Particularly, a latest study revealed that the activated Cas13a provided bacterial hosts with a "passive protection" mechanism to defend against DNA phage infection by inducing cell growth arrest in infected cells, which is especially significant as it endows Cas13a, a RNA-targeting CRISPR effector, with mount defense against both RNA and DNA invaders.

DDR2, a discoidin domain receptor, is a marker of periosteal osteoblast and osteoblast progenitors.

Introduction: The periosteum has a bilayered structure that surrounds cortical bone. The outer layer is rich in connective tissue and fibroblasts, while the inner layer in contact with the cortical surface of the bone predominantly consists of osteoblasts and osteoblast progenitors. The identification of cell-specific surface markers of the bilayered structure of the periosteum is important for the purpose of tissue regeneration.

Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis.

Due to their bacterial ancestry, many components of mitochondria share structural similarities with bacteria. Release of molecular danger signals from injured cell mitochondria (mitochondria-derived damage-associated molecular patterns, mito-DAMPs) triggers a potent inflammatory response, but their role in fibrosis is unknown. Using liver fibrosis resistant/susceptible mouse strain system, we demonstrate that mito-DAMPs released from injured hepatocyte mitochondria (with mtDNA as major active component) directly activate hepatic stellate cells, the fibrogenic cell in the liver, and drive liver scarring.

An Alternative Splicing of STING Modulated Anti-RNA Virus Responses by Targeting MDA5-LGP2 and IRF3.

The stimulator of IFN genes (STING; also known as MITA, TMEM173, MPYS, or ERIS) is generally regarded as a key adaptor protein for sensing pathogenic DNA genomes. However, its role in RNA viral signaling as part of the innate immunity system remains controversial. In this study, we identified two isoforms of STING (a full-length STING [tSTING-FL] and a STING short isoform [tSTING-mini]) in the Chinese tree shrew (), a close relative of primates.

HIV-1 Drug Resistance in ART-Naïve Individuals in Myanmar.

Background: Estimating the prevalence and characterizing the transmission of HIV-1 drug resistance in treatment-naïve individuals are very important in the prevention and control of HIV/AIDS. As one of the areas most affected by HIV/AIDS, few data are currently available for HIV-1 drug resistance in antiretroviral therapy (ART)-naïve individuals in Myanmar, which borders Yunnan, China.

Methods: HIV-1 sequences from ART-naïve HIV-1-infected individuals during 2008 and 2014 in Myanmar were retrieved from our previous studies.

SARS-CoV-2 and viral sepsis: observations and hypotheses.

Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients.

Author Correction: Bis-biguanide dihydrochloride inhibits intracellular replication of M. tuberculosis and controls infection in mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3-CD8+ T cells.

The lack of sufficient functional tumor-infiltrating lymphocytes in the tumor microenvironment (TME) is one of the primary indications for the poor prognosis of patients with cancer. In this study, we developed an Erbitux-based IL-21 tumor-targeting fusion protein (Erb-IL21) to prolong the half-life and improve the antitumor efficacy of IL-21. Compared with Erb-IL2, Erb-IL21 demonstrated much lower toxicity in vivo.

Pre-existing heterologous T-cell immunity and neoantigen immunogenicity.

Neoantigens are tumor-specific mutated proteins that are exempt from central tolerance and are therefore capable of efficiently eliciting effective T-cell responses. The identification of immunogenic neoantigens in tumor-specific mutated proteins has promising clinical implications for cancer immunotherapy. However, the factors that may contribute to neoantigen immunogenicity are not yet fully understood.

Tumoral PD-1hiCD8+ T cells are partially exhausted and predict favorable outcome in triple-negative breast cancer.

Tumor-infiltrating PD-1hi dysfunctional CD8+ T cells have been identified in several tumors but largely unexplored in breast cancer (BC). Here we aimed to extensively explore PD-1hiCD8+ T cells in BC, focusing on the triple-negative BC (TNBC) subtype. Flow cytometry was used to study the phenotypes and functions of CD8+ T-cell subsets in peripheral blood and surgical specimens from treatment-naive BC patients.