A T-Cell Inspired Sonoporation System Enhances Low-Dose X-Ray-Mediated Pyroptosis and Radioimmunotherapy Efficacy by Restoring Gasdermin-E Expression.

Genome editing has the potential to improve the unsatisfactory therapeutic effect of antitumor immunotherapy. However, the cell plasma membrane prevents the entry of almost all free genome-manipulation agents. Therefore, a system can be spatiotemporally controlled and can instantly open the cellular membrane to allow the entry of genome-editing agents into target cells is needed.

A Bioinspired Immunostimulatory System for Inducing Powerful Antitumor Immune Function by Directly Causing Plasma Membrane Rupture.

The Gasdermin protein is a membrane disruptor that can mediate immunogenic pyroptosis and elicit anti-tumor immune function. However, cancer cells downregulate Gasdermin and develop membrane repair mechanisms to resist pyroptosis. Therefore, an artificial membrane disruptor (AMD) that can directly mediate membrane rupture in pyroptosis-deficient cells and induce antitumor immune responses in a controllable manner will be valuable in preclinical and clinical research.

A CTL-Inspired Killing System Using Ultralow-Dose Chemical-Drugs to Induce a Pyroptosis-Mediated Antitumor Immune Function.

A Cytotoxic T lymphocyte-inspired system capable of using ultralow-dose chemical drugs to manipulate cell death is needed to investigate the antitumor immunotherapy. Recent studies reveal pyroptosis promotes antitumor immune function. However, high-dose chemotherapy leads to cytokine release syndrome by pyroptosis.

Molecular Characterization and Phylogenetic Analysis of the 2019 Dengue Outbreak in Wenzhou, China.

In 2019, a dengue outbreak occurred with 290 confirmed cases in Wenzhou, a coastal city in southeast China. To identify the origin of the dengue virus (DENV) from this outbreak, viral RNA was extracted from four serum samples and sequenced for whole genome analysis. Then, phylogenetic analysis, gene mutation, secondary structure prediction, selection pressure analysis, and recombination analysis were performed.

Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns.

Urinary exosomal long noncoding RNAs serve as biomarkers for early detection of non-small cell lung cancer.

Objective: Increasing the efficiency of early diagnosis using noninvasive biomarkers is crucial for enhancing the survival rate of lung cancer patients. We explore the differential expression of non-small cell lung cancer (NSCLC)-related long noncoding RNAs (lncRNAs) in urinary exosomes in NSCLC patients and normal controls to diagnose lung cancer.

Methods: A differential expression analysis between NSCLC patients and healthy controls was performed using microarrays.

Regulation of Intrinsic and Bystander T Follicular Helper Cell Differentiation and Autoimmunity by Tsc1.

T Follicular helper (Tfh) cells promote germinal center (GC) B cell responses to develop effective humoral immunity against pathogens. However, dysregulated Tfh cells can also trigger autoantibody production and the development of autoimmune diseases. We report here that Tsc1, a regulator for mTOR signaling, plays differential roles in Tfh cell/GC B cell responses in the steady state and in immune responses to antigen immunization.

The Role of TSC1 in the Macrophages Against Infection.

() is an estuarine bacterium that is capable of causing rapidly fatal infection in humans. Proper polarization and bactericidal activity of macrophages play essential roles in defending against invading pathogens. How macrophages limit infection remains not well understood.

Clinical Outcomes of "U" Route Transforaminal Percutaneous Endoscopic Lumbar Discectomy in Chronic Pain Patients with Lumbar Spinal Stenosis Combined with Disc Herniation.

Introduction: "U" route transforaminal percutaneous endoscopic lumbar discectomy (PELD) was introduced for lumbar spinal stenosis (LSS) combined with disc herniation (DH) treatment. This study aims to explore the efficacy and safety of "U" route PELD on chronic pain patients with LSS combined with DH.

Methods: Degenerative LSS combined with DH patients who underwent "U" route PELD were reexamined, and 80 patients were recruited and followed up for 2 years.

NLRP3 and mTOR Reciprocally Regulate Macrophage Phagolysosome Formation and Acidification Against Infection.

The marine bacterium causes potentially fatal bloodstream infections, typically in patients with chronic liver diseases. The inflammatory response and anti-bacterial function of phagocytes are crucial for limiting bacterial infection in the human hosts. How affects macrophages after phagocytosis is unclear.

Efficacy and safety of thrombopoietin receptor agonists in children with chronic immune thrombocytopenia: a meta-analysis.

Background And Aim: Thrombopoietin receptor agonists (TPO-RAs) have been shown to be safe and effective for adults with chronic immune thrombocytopenia (ITP). The aim of this meta-analysis is to assess the efficacy and safety of thrombopoietin receptor agonists for children with chronic ITP.

Materials And Methods: Clinical randomized controlled trials (RCTs) evaluating the efficacy and safety of TPO-RAs in pediatric ITP patients published up to June 2017 were retrieved from PubMed, Cochrane Library, and Embase databases.

Vibrio vulnificus induces mTOR activation and inflammatory responses in macrophages.

Vibrio vulnificus (V. vulnificus), a Gram-negative marine bacterium, can cause life-threatening primary septicemia, especially in patients with liver diseases. How V.

Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation.

Signals from the T-cell receptor (TCR) and γ-chain cytokine receptors play crucial roles in initiating activation and effector/memory differentiation of CD8 T-cells. We report here that simultaneous deletion of both diacylglycerol kinase (DGK) α and ζ (DKO) severely impaired expansion of CD8 effector T cells and formation of memory CD8 T-cells after Listeria monocytogenes infection. Moreover, ablation of both DGKα and ζ in preformed memory CD8 T-cells triggered death and impaired homeostatic proliferation of these cells.

Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity.

Development of effective immune therapies for cancer patients requires better understanding of hurdles that prevent the generation of effective antitumor immune responses. Administration of α-galactosylceramide (α-GalCer) in animals enhances antitumor immunity via activation of the invariant NKT (iNKT) cells. However, repeated injections of α-GalCer result in long-term unresponsiveness or anergy of iNKT cells, severely limiting its efficacy in tumor eradication.

MicroRNA-34a enhances T cell activation by targeting diacylglycerol kinase ζ.

The engagement of the T cell receptor (TCR) induces the generation of diacylglycerol (DAG), an important second messenger activating both the Ras/Erk and PKCθ/NFκB pathways. DAG kinases (DGKs) participate in the metabolism of DAG by converting it to phosphatidic acid. DGKζ has been demonstrated to be able to inhibit DAG signaling following TCR engagement.

The -590C/T polymorphism in the IL-4 gene and the risk of cancer: a meta-analysis.

Interleukin-4 (IL-4) plays an important role in the pathogenesis of cancer. The -590C/T polymorphism in the IL-4 gene has been implicated in susceptibility to cancer, but the results have been inconclusive. The aim of this study was to analyze the association between this polymorphism with the risk of cancer by meta-analysis.

Tumor suppressor TSC1 is critical for T-cell anergy.

T-cell anergy is a state of T cells that is hyporesponsive to stimulation via the T-cell receptor and costimulatory molecules and is thought to be important for self-tolerance. How T-cell anergy is regulated is still poorly understood. We report here that tuberous sclerosis (TSC)1 is critical for T-cell anergy.

Chronic activation of the kinase IKKβ impairs T cell function and survival.

Activation of the transcription factor NF-κB is critical for cytokine production and T cell survival after TCR engagement. The effects of persistent NF-κB activity on T cell function and survival are poorly understood. In this study, using a murine model that expresses a constitutively active form of inhibitor of NF-κB kinase β (caIKKβ) in a T cell-specific manner, we demonstrate that chronic inhibitor of NF-κB kinase β signaling promotes T cell apoptosis, attenuates responsiveness to TCR-mediated stimulation in vitro, and impairs T cell responses to bacterial infection in vivo.

Regulation of T-cell survival and mitochondrial homeostasis by TSC1.

The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism. It associates with multiple proteins and forms two distinct signaling complexes, mTORC1 and mTORC2. Accumulating evidence has revealed critical roles for intact mTOR signaling during T-cell activation and responses to microbial infection.

Receptor signaling in immune cell development and function.

Immune cell development and function must be tightly regulated through cell surface receptors to ensure proper responses to pathogen and tolerance to self. In T cells, the signal from the T-cell receptor is essential for T-cell maturation, homeostasis, and activation. In mast cells, the high-affinity receptor for IgE transduces signal that promotes mast cell survival and induces mast cell activation.