Phenotypic assessment of dendritic cell maturation by cost-effective custom ELISA assays.

Dendritic cells (DCs) are professional antigen-presenting cells that are pivotal in operating tumor immunosurveillance and orchestrating anticancer immune responses. Endowed with phagocytic and migratory capacities, DCs can capture and process tumor antigens, travel to lymphoid organs and prime naïve T cells, altogether leading to the clonal expansion of cytotoxic T lymphocytes (CTLs) that can specifically target and lyse cancer cells. Additionally, DCs contribute to the formation of immunological memory, ensuring durable therapeutic effects and long-term surveillance against tumor recurrence.

How macrophages use extracellular calreticulin to chase their prey.

Recent findings reveal that macrophages actively control clearance by desialylating target cells via NEU1 and releasing cathepsin-cleaved calreticulin (CALR) to mark them for phagocytosis. This uncovers a dual role for CALR as immune activator or repressor, depending on its form and context, with distinct implications for cancer immunity.

Sepiolite-Based Nanogenerator Driven by Water Evaporation.

This work introduces a new type of water evaporation-driven nanogenerator (S-WEG) utilizing the natural mineral sepiolite, which capitalizes on its hierarchical nanoporous architecture and intrinsic hydrophilicity to harvest energy from ambient humidity through capillary-driven evaporation. The S-WEG, fabricated via a facile drop-coating drying method, demonstrates remarkable mechanical flexibility and sustained operational reliability. Our results demonstrate that by optimizing evaporation height and width, the S-WEG can generate a short-circuit current of ~0.

Neutralization of acyl coenzyme A binding protein for the experimental prevention and treatment of hepatocellular carcinoma.

Acyl coenzyme A binding protein (ACBP encoded by diazepam binding inhibitor DBI) is involved in non-malignant liver diseases. Here, we show that DBI mRNA and circulating ACBP/DBI levels are increased in patients with hepatocellular carcinoma (HCC). We investigated its role in hepatocarcinogenesis in mice, inhibiting ACBP/DBI by three methods: (1) inducible whole-body or liver-specific knockout of DBI, (2) a point mutation of the ACBP/DBI receptor (GABRG2), and (3) induction of autoantibodies neutralizing ACBP/DBI.

Gut Microbiota Modulation through Akkermansia spp. Supplementation Increases CAR T-cell Potency.

Unlabelled: This study investigates the clinical relevance of the gut microbiome at taxonomic and metabolic levels in anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, both in patients and in a preclinical syngeneic tumor model. Patients with B-cell lymphoma treated with CD19 CAR T cells exhibited profound intestinal dysbiosis, exacerbated after CAR T-cell infusion. This dysbiosis was characterized by low bacterial richness, low soluble MAdCAM-1, and loss of Akkermansia species, associated with resistance to therapy.

Dexmedetomidine induces immunogenic cancer cell death and sensitizes tumors to PD-1 blockade.

Background: Local anesthetics promote anticancer immune responses. A machine learning-based algorithm trained with information on the biological effects and molecular descriptors of analgesics, anesthetics, hypnotics and opioids predicted antitumor effects for dexmedetomidine (DEX). DEX is a sedative acting as an alpha2-adrenoceptor (ADRA2) agonist.

Patritumab deruxtecan induces immunogenic cell death.

Antibody-drug conjugates (ADCs) enable targeted delivery of cytotoxic payload to cancer cells. Here, we characterized the mode of action of the ADC patritumab deruxtecan, which is a monoclonal antibody specific for Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3, best known as HER3) coupled to the topoisomerase-I inhibitor DXd. Patritumab deruxtecan decreased viability and induced the relocation of calreticulin fused to green fluorescent protein (CALR-GFP) to the periphery of human osteosarcoma U2OS cells engineered to express HER3 but not in their parental counterparts only expressing the CALR-GFP biosensor.

Mitochondrial DNA transfer between malignant cells and T lymphocytes shapes the cancer-immunity dialogue.

Nonmutated mitochondrial DNA (mtDNA) from T lymphocytes can be incorporated into cancer cells bearing mutated mtDNA to repair their bioenergetic deficiency. However, a recent paper by Ikeda et al. indicates that mutated mtDNA from malignant cells can also be transferred into tumor-infiltrating T lymphocytes to subvert their function in cancer immunosurveillance.

Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients.

The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8 T cell activation without exhaustion.

Potent antiviral activity of simnotrelvir against key epidemic SARS-CoV-2 variants with a high resistance barrier.

Simnotrelvir is an oral small-molecule antiviral agent targeting the 3C-like protease (3CL) of SARS-CoV-2, proven effective against the Delta variant with favorable pharmacokinetics and safety in preclinical study. In this study, we further evaluated the antiviral efficacy of simnotrelvir against a range of emerging Omicron variants, including BA.1, BA.

The MCM6-c-Myc positive feedback loop mediates bladder cancer progression and cisplatin resistance.

Chemotherapy remains a cornerstone in the treatment of bladder cancer (BLCA); however, the development of chemoresistance substantially limits its efficacy and significantly affects patient survival. Thus, elucidating the molecular mechanisms underlying BLCA chemoresistance is critical to improving patient outcomes. Our study identified MCM6 as an oncogene that facilitates BLCA proliferation and invasion and is linked to cisplatin resistance.

Sn-carbon nanocomposite anode for all-solid-state chloride-ion batteries operating at room temperature.

All-solid-state chloride-ion batteries promise high theoretical energy density and room-temperature operation. However, conventional Sn anodes suffer from low material utilization attributed to large particle size and volume expansion. Here, nano-sized Sn particles in an N-doped carbon framework are used as an anode, resulting in ∼12% higher capacity compared to conventional Sn, due to improved Sn utilization and suppression of volume expansion.

A machine learning-based immune response signature to facilitate prognosis prediction in patients with endometrial cancer.

Endometrial cancer is the most prevalent form of gynecologic malignancy, with a significant surge in incidence among youngsters. Although the advent of the immunotherapy era has profoundly improved patient outcomes, not all patients benefit from immunotherapy; some patients experience hyperprogression while on immunotherapy. Hence, there is a pressing need to further delineate the distinct immune response profiles in patients with endometrial cancer to enhance prognosis prediction and facilitate the prediction of immunotherapeutic responses.

AI-based classification of anticancer drugs reveals nucleolar condensation as a predictor of immunogenicity.

Background: Immunogenic cell death (ICD) inducers are often identified in phenotypic screening campaigns by the release or surface exposure of various danger-associated molecular patterns (DAMPs) from malignant cells. This study aimed to streamline the identification of ICD inducers by leveraging cellular morphological correlates of ICD, specifically the condensation of nucleoli (CON).

Methods: We applied artificial intelligence (AI)-based imaging analyses to Cell Paint-stained cells exposed to drug libraries, identifying CON as a marker for ICD.

High-resolution imaging atlas reveals the context-dependent role of pancreatic sympathetic innervation in diabetic mice.

A better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in the islets of adult wild-type (WT) and diabetic mice.

Cytoplasmic HMGB2 orchestrates CALR translocation in the course of immunogenic cell death.

A recent in vitro study showed that pharmacological inhibition of the nuclear export receptor XPO1 suppresses oxaliplatin-induced nuclear release of HMGB1 and HMGB2, as well as the translocation of CALR to the plasma membrane. Moreover, cell-targeted-HMGB2 protein potently induced CALR exposure, even in the absence of oxaliplatin.

MOTS-c relieves hepatocellular carcinoma resistance to TRAIL-induced apoptosis under hypoxic conditions by activating MEF2A.

Background: Mitochondrial ORF of the 12S rRNA type-c (MOTS-c) as an AMPK agonist can regulate the expression of adaptive nuclear genes to promote cell homeostasis. However, the investigation of MOTS-c in hepatocellular carcinoma (HCC) is insufficient. This study aims to reveal the role of MOTS-c on HCC cell apoptosis.

A global lipid map of severe fever with thrombocytopenia syndrome virus infection reveals glycerophospholipids as novel prognosis biomarkers.

Unlabelled: Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressing infectious disease caused by a novel bunyavirus characterized by high fever, thrombocytopenia, and multiple organ damage. While lipids play an important role in viral infections, the specific alterations in lipid metabolism during SFTSV infection remain unclear. This study aimed to elucidate the global lipid metabolic profiles of SFTS patients with mild, severe, and fatal outcomes.

Integrating Bulk and Single-cell RNA-seq to Construct a Macrophage-related Prognostic Model for Prognostic Stratification in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a poor prognostic subtype of breast cancer due to limited treatment. Macrophage plays a critical role in tumor growth and survival. Our study intends to explore the heterogeneity of macrophage in TNBC and establish a macrophage-related prognostic model for TNBC prognostic stratification.

Immunogenic cell death inducers and PD-1 blockade as neoadjuvant therapy for rectal cancer.

Immuno-oncological cancer management is shifting to neoadjuvant treatments. In patients with gastrointestinal cancers, particularly locally advanced rectal cancer, neoadjuvant chemoimmunotherapy often induce complete responses, hence avoiding surgical intervention. Recent clinical trials indicate that combinations of oxaliplatin-based chemotherapy and PD-1/PD-L1-targeting immunotherapy can be safely administered before surgery with curative intent.

Escin ameliorates CUMS-induced depressive-like behavior via BDNF/TrkB/CREB and TLR4/MyD88/NF-κB signaling pathways in rats.

Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear.

Graphene Microflower by Photothermal Marangoni-Induced Fluid Instability for Omnidirectional Broadband Photothermal Conversion.

2-D carbon-based materials are well-known for their broadband absorption properties for efficient solar energy conversion. However, their high reflectivity poses a challenge for achieving efficient omnidirectional light absorption. Inspired by the multilevel structures of the flower, a Graphene Microflower (GM) material with gradient refractive index surface was fabricated on polymer substrates using the UV-intense laser-induced phase explosion technique under the synergistic design of the photothermal Marangoni effect and the fluid instability principle.