Distinctive function of Tetraspanins: Implication in viral infections.

Harboring four transmembrane domains in their structural hallmark, Tetraspanins (Tspans) are a family of glycoproteins with pivotal functions in a variety of biological and cellular processes. Through interacting laterally with each other or specific membrane proteins, Tspans organize tetraspanin-enriched microdomains (TEMs), modulating cellular signaling, adhesion, fusion, and proliferation. An abundance of evidence has identified the multiple functions in the progression of cancer as well as the underlying molecular mechanisms.

Real-Time 0.89 THz Terahertz Imaging with High-Electron-Mobility Transistor Detector and Hydrogen Cyanide Laser for Non-Destructive Nut Detection.

We present a method for real-time terahertz imaging that employs a hydrogen cyanide (HCN) laser as a terahertz source at 0.89 THz and an AlGaN/GaN high-electron-mobility transistor (HEMT) terahertz detector as a camera. We developed an HCN laser and constructed a transmission imaging system based on it.

Purine metabolism in bone marrow microenvironment inhibits hematopoietic stem cell differentiation under microgravity.

Background: Spaceflight and microgravity environments have been shown to cause significant health impairments, including bone loss, immune dysfunction, and hematopoietic disorders. Hematopoietic stem cells (HSCs), as progenitors of the hematopoietic system, are critical for the continuous renewal and regulation of immune cells. Therefore, elucidating the regulatory mechanisms governing HSC fate and differentiation in microgravity environments is of paramount importance.

Augmentation of antiviral immune response induced by perturbation of CD82 under microgravity condition.

Exposure to microgravity has become the primary factor threatening astronauts' health. Immunity is dysregulated rapidly following spaceflight, and reactivation of latent virus has been observed. However, systematic studies and molecular mechanisms of the adverse impact of microgravity on the antiviral immune response are still elusive.

Musculoskeletal adverse events associated with CDK4/6 inhibitors: a real-world study using FDA Adverse Event Reporting System (FAERS) database.

Objective: Cyclin-dependent kinase (CDK)-4/6 inhibitors have significantly improved outcomes in several cancers but can also induce various organ system toxicities, including musculoskeletal disorders. This study aimed to comprehensively characterize the musculoskeletal adverse events (MSAEs) associated with CDK4/6 inhibitors based on real-world data.

Methods: Reports of MSAEs linked to CDK4/6 inhibitors from the first quarter (Q1) of 2015 and 2023 Q4 were extracted from the FAERS.

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Age-Dependent Bi-Phasic Dynamics of Ly49CD8 Regulatory T Cell Population.

Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4Foxp3 regulatory T cells (Tregs) have been well documented.

The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation.

During persistent antigen stimulation, exhausted CD8 T cells are continuously replenished by self-renewing stem-like T cells. However, how CD8 T cells adapt to chronic stimulation remains unclear. Here, we show that persistent antigen stimulation primes chromatin for regulation by the redox-sensing KEAP1-NRF2 pathway.

Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases.

Group 2 innate lymphoid cells (ILC2s) are key players in type 2 immunity, but whether they can be directly activated by microbial ligands remain uncertain. In this study, we observed a positive correlation between blood endotoxin (LPS) levels and circulating ILC2s in allergic patients. , LPS robustly induced ILC2 proliferation and production of type 2 effector cytokines.

Corrigendum: Into the storm: the imbalance in the yin-yang immune response as the commonality of cytokine storm syndromes.

[This corrects the article DOI: 10.3389/fimmu.2024.

The Laws of Attraction: Chemokines as Critical Mediators in Cancer Progression and Immunotherapy Response in Bladder Cancer.

Bladder cancer (BCa) is a prevalent urogenital malignancy, characterized by a myriad of genetic and environmental risk factors that drive its progression. Approximately 75% of bladder tumors are non-muscle-invasive at diagnosis. For such cases, bladder preservation is often feasible with intravesical chemotherapy or immunotherapy.

A peptide encoded by upstream open reading frame of binds to tropomyosin receptor kinase B and promotes glioblastoma growth in mice.

MYC promotes tumor growth through multiple mechanisms. Here, we show that, in human glioblastomas, the variant transcript encodes a 114-amino acid peptide, MYC pre-mRNA encoded protein (MPEP), from the upstream open reading frame (uORF) . Secreted MPEP promotes patient-derived xenograft tumor growth in vivo, independent of MYC through direct binding, and activation of tropomyosin receptor kinase B (TRKB), which induces downstream AKT-mTOR signaling.

Dynamic structural remodeling of LINC01956 enhances temozolomide resistance in -methylated glioblastoma.

The mechanisms underlying stimuli-induced dynamic structural remodeling of RNAs for the maintenance of cellular physiological function and survival remain unclear. Here, we showed that in promoter-methylated glioblastoma (GBM), the RNA helicase DEAD-box helicase 46 (DDX46) is phosphorylated by temozolomide (TMZ)-activated checkpoint kinase 1 (CHK1), resulting in a dense-to-loose conformational change and an increase in DDX46 helicase activity. DDX46-mediated tertiary structural remodeling of LINC01956 exposes the binding motifs of LINC01956 to the 3' untranslated region of O-methylguanine DNA methyltransferase ().

Into the storm: the imbalance in the yin-yang immune response as the commonality of cytokine storm syndromes.

There is a continuous cycle of activation and contraction in the immune response against pathogens and other threats to human health in life. This intrinsic yin-yang of the immune response ensures that inflammatory processes can be appropriately controlled once that threat has been resolved, preventing unnecessary tissue and organ damage. Various factors may contribute to a state of perpetual immune activation, leading to a failure to undergo immune contraction and development of cytokine storm syndromes.

Tenovin-6 exhibits inhibitory effects on the growth of Sonic Hedgehog (SHH) medulloblastoma, as evidenced by both in vitro and in vivo studies.

Medulloblastoma (MB) is the most common malignant brain tumor in children. Within MB, tumors driven by the Sonic Hedgehog (SHH) pathway represent the most heterogeneous subtype, known as SHH subtype medulloblastoma (SHH-MB). Tenovin-6, a recognized p53 activator, has been demonstrated to inhibit autophagy and modulate sirtuin activity, underscoring its potential as a novel therapeutic agent across various malignancies.

Epithelial organoid supports resident memory CD8 T cell differentiation.

Resident memory T cells (TRMs) play a vital role in regional immune defense. Although laboratory rodents have been extensively used to study fundamental TRM biology, poor isolation efficiency and low cell survival rates have limited the implementation of TRM-focused high-throughput assays. Here, we engineer a murine vaginal epithelial organoid (VEO)-CD8 T cell co-culture system that supports CD8 TRM differentiation.

Heterogeneous stiffness of the bone marrow microenvironment regulates the fate decision of haematopoietic stem and progenitor cells.

The bone marrow (BM) niches are the complex microenvironments that surround cells, providing various external stimuli to regulate a range of haematopoietic stem cell (HSC) behaviours. Recently, it has been proposed that the fate decision of HSCs is often correlated with significantly altered biophysical signals of BM niches. To thoroughly elucidate the effect of mechanical microenvironments on cell fates, we constructed 2D and 3D cell culture hydrogels using polyacrylamide to replicate the mechanical properties of heterogeneous sub-niches, including the inherent rigidity of marrow adipose tissue (2 kPa), perivascular tissue (8 kPa) and endosteum region (35 kPa) in BM.

Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.

Bone tissue represents the most frequent site of cancer metastasis. We developed a hemichannel-activating antibody, Cx43-M2. Cx43-M2, directly targeting osteocytes in situ, activates osteocytic hemichannels and elevates extracellular ATP, thereby inhibiting the growth and migration of cultured breast and osteosarcoma cancer cells.

Distinct roles of TREM2 in central nervous system cancers and peripheral cancers.

Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM.