High CD38 expression defines a mitochondrial function-adapted CD8 T cell subset with implications for lung cancer immunotherapy.

Despite identifying specific CD8 T cell subsets associated with immunotherapy resistance, the molecular pathways driving this process remain elusive. Given the potential role of CD38 in regulating CD8 T cell function, we aimed to investigate the accumulation of CD38CD8 T cells in lung cancer and explore its role in immunotherapy resistance. Phenotypic analysis of tumoral CD8 T cells from both lung cancer patients and immunotherapy-resistant preclinical models revealed that CD38-expressing CD8 T cells consist of CD38 and CD38 subsets.

Assessing live microbial therapeutic transmission.

The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology.

Portable UV-C device to treat high flow of infectious aerosols generated during clinical respiratory care.

Respiratory interventions including noninvasive ventilation, continuous positive airway pressure and high-flow nasal oxygen generated infectious aerosols may increase risk of airborne disease (SARS-CoV-2, influenza virus) transmission to healthcare workers. We developed and tested a prototype portable UV-C device to sterilize high flows of viral-contaminated air from a simulated patient source at airflow rates of up to 100 l/m. Our device consisted of a central quartz tube surrounded 6 high-output UV-C lamps, within a larger cylinder allowing recirculation past the UV-C lamps a second time before exiting the device.

Hyperreactive B cells instruct their elimination by T cells to curb autoinflammation and lymphomagenesis.

B cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not.

Folinic acid as a treatment for autism in children: A within-subjects open-label study on safety and efficacy.

The folate cycle has been implicated in the pathophysiology of autism due to its role in the glutathione oxidative stress pathway, amino acid and DNA methylation reactions, and neurotransmitter synthesis pathway. Previous research on folinic acid supplementation in autistic children has suggested potential benefits. The primary aim of this pilot study was to determine the safety, feasibility and efficacy of oral folinic acid in improving communication and behaviour in autistic children.

Unveiling the hidden network of STING's subcellular regulation.

A new study deconvolutes the systems-level control of the cGAS-STING pathway and identifies many novel regulators of STING biology. This was made possible by optical pooled screening (OPS), which enables high-dimensional imaging of millions of gene-edited cells, showcasing the future of CRISPR screening.

Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation.

Background: Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver.

Inhibitors of acetohydroxyacid synthase as promising agents against non-tuberculous mycobacterial diseases.

Acetohydroxyacid synthase (AHAS), exclusively present in microorganisms and plants, is a promising target for several herbicides due to its catalytic role in the branched-chain amino acid biosynthetic pathway. Previous studies have shown that K13787, a pyrazolopyrimidine sulfonamide AHAS inhibitor, was moderately effective against pulmonary infection caused by M. tuberculosis and nontuberculous mycobacteria (NTM).

Guidelines for preparation and flow cytometry analysis of human nonlymphoid tissue DC.

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs, and various nonlymphoid tissues. Within this article, detailed protocols are presented that allow for the generation of single-cell suspensions from human nonlymphoid tissues including lung, skin, gingiva, intestine as well as from tumors and tumor-draining lymph nodes with a subsequent analysis of dendritic cells by flow cytometry. Further, prepared single-cell suspensions can be subjected to other applications including cellular enrichment procedures, RNA sequencing, functional assays, etc.

Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis.

Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort.

Hamartomatous Polyp of the Palatine Tonsil in an Adolescent: A Case Report.

A hamartoma is a benign tumor that arises from the disorganized proliferation of tissue and can occur anywhere in the body. Hamartomas are notably found in the lung, skin, heart, brain, and breast, while their occurrence in the head and neck is rare. We describe a case involving a 17-year-old male patient who presented with a mass in a unilateral palatine tonsil, discovered incidentally.

Precision models in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents a global health challenge, and ranks among one of the most prevalent and deadliest cancers worldwide. Therapeutic advances have expanded the treatment armamentarium for patients with advanced HCC, but obstacles remain. Precision oncology, which aims to match specific therapies to patients who have tumours with particular features, holds great promise.

Genetic immune escape in cancer: timing and implications for treatment.

Genetic immune escape (GIE) alterations pose a significant challenge in cancer by enabling tumors to evade immune detection. These alterations, which can vary significantly across cancer types, may often arise early in clonal evolution and contribute to malignant transformation. As tumors evolve, GIE alterations are positively selected, allowing immune-resistant clones to proliferate.

Interferon response and epigenetic modulation by mutations drive ovarian tumor immunogenicity.

Cell-intrinsic mechanisms of immunogenicity in ovarian cancer (OC) are not well understood. Damaging mutations in the SWI/SNF chromatin remodeling complex, such as (BRG1), are associated with improved response to immune checkpoint blockade; however, the mechanism by which this occurs is unclear. We found that loss in OC models resulted in increased cancer cell-intrinsic immunogenicity, characterized by up-regulation of long-terminal RNA repeats, increased expression of interferon-stimulated genes, and up-regulation of antigen presentation machinery.

Integrative analysis identifies the atypical repressor E2F8 as a targetable transcriptional activator driving lethal prostate cancer.

Acquired resistance to androgen receptor (AR)-targeted therapies underscores the need to identify alternative therapeutic targets for treating lethal prostate cancer. In this study, we evaluated the prognostic significance of 1635 human transcription factors (TFs) by analyzing castration-resistant prostate cancer (CRPC) datasets from the West and East Stand Up to Cancer (SU2C) cohorts. Through this screening approach, we identified E2F8, a putative transcriptional repressor, as a TF consistently associated with poorer patient outcomes in both cohorts.

CAR-armored-cell therapy in solid tumor treatment.

Over the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a revolutionary immunotherapeutic approach to combat cancer. This therapy constructs a CAR on the surface of T cells through genetic engineering techniques. The CAR is formed from a combination of antibody-derived or ligand-derived domains and T-cell receptor (TCR) domains.

Gut microbiota strain richness is species specific and affects engraftment.

Despite the fundamental role of bacterial strain variation in gut microbiota function, the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments.

Unveiling Biomarkers in Head and Neck Squamous Cell Carcinoma through Bioinformatics: The Role of and .

Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer, ranking sixth in global cancer incidence. Identifying molecular drivers of tumorigenesis and metastasis is essential for early detection and treatment. This study analyzed gene expression profiles from three datasets (GSE6791, GSE29330, and GSE58911) to identify differentially expressed genes (DEGs) in HNSCC.

Association Between Frequency of Away-From-Home Meals and Prevalence of Inflammatory Sinonasal Diseases: A Population-Based Cross-Sectional Study.

At the beginning of the COVID-19 pandemic, people had to stay at home due to quarantine, and the food delivery industry grew significantly. Concerns have been raised regarding the popularity of away-from-home (AFH) meals and their impact on health. In this study, we evaluated the association between the frequency of AFH meals and the prevalence of allergic rhinitis (AR) and chronic rhinosinusitis (CRS).

Intravenous administration of blood-brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system.

Delivery of biomacromolecules to the central nervous system (CNS) remains challenging because of the restrictive nature of the blood-brain barrier (BBB). We developed a BBB-crossing conjugate (BCC) system that facilitates delivery into the CNS through γ-secretase-mediated transcytosis. Intravenous administration of a BCC10-oligonucleotide conjugate demonstrated effective transportation of the oligonucleotide across the BBB and gene silencing in wild-type mice, human brain tissues and an amyotrophic lateral sclerosis mouse model.

Outcome of SARS-CoV-2 reinfection depends on genetic background in female mice.

Antigenically distinct SARS-CoV-2 variants increase the reinfection risk for vaccinated and previously exposed population due to antibody neutralization escape. COVID-19 severity depends on many variables, including host immune responses, which differ depending on genetic predisposition. To address this, we perform immune profiling of female mice with different genetic backgrounds -transgenic K18-hACE2 and wild-type 129S1- infected with the severe B.