Cracking the Valence Code: Patterned Facial Kinematics and Neural Signatures of Emotional Expressions in Mice.

Despite advances in linking mouse facial expressions to emotional states, the specific facial features and neural signatures remain elusive. An artificial intelligence (AI)-based framework that decodes mouse facial expressions is presented, revealing stable valence and arousal dimensions analogous to those described in human emotion models. Facial expressions emerge as robust indicators of positive and negative emotional responses, validated through pharmacological manipulations, while responses to hallucinogens highlight the potential of valence-specific prototype modeling for interpreting previously uncharacterized emotional states.

hCCL19-expressing recombinant Newcastle disease virus boosts CAR T cell infiltration and efficacy in solid tumor.

Background: Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematological malignancies; however, it faces significant challenges in treating solid tumors, including limited immune infiltration into tumor tissues and immunosuppressive tumor microenvironment. Oncolytic viruses (OVs), which selectively destroy cancer cells and trigger antitumor immune responses, offer a compelling solution to these challenges. Newcastle disease virus (NDV) is a natural OV that exhibits antitumor activity with minimal side effects in clinical studies.

Vapor I-Mediated Robust Aggregation/Etching of Silver Nanoparticles for Sensitive and On-Site SERS Monitoring of Iodine in Seawater.

While oceanic iodine plays a critical role in monitoring marine pollution and biogeochemical cycles, existing detection methods suffer from compromised sensitivity, laborious pretreatment, and field-incompatible operation. Herein, we present a vapor-phase molecular recognition strategy that leverages iodine (I)-induced structural transformation of silver nanoparticles (AgNPs) for surface-enhanced Raman scattering (SERS) indirect detection, with rhodamine 6G (Rh6G) as a Raman probe of seawater iodine. Spectroscopic and electron microscopic results showed that I induced stronger sequential aggregation and anisotropic etching of nanoparticles than I, effectively suppressing SERS enhancement.

Regulator of chromosome condensation 1 promotes hepatocellular carcinoma proliferation cell-division-cycle-associated-8 dependent phosphoinositide 3-kinase/protein kinase B signaling.

Background: Hepatocellular carcinoma (HCC) ranks among the most prevalent and deadly malignancies, characterized by a high recurrence rate. Regulator of chromosome condensation 1 (RCC1) serves as a principal guanine nucleotide exchange factor for ras-related nuclear protein guanosine triphosphatase (GTPase) and is implicated in various cancers. However, the role of RCC1 in HCC remains unexplored.

Tobacco Smoking Rewires Cell Metabolism by Inducing GAPDH Succinylation to Promote Lung Cancer Progression.

Unlabelled: Patient behavior and physiology can directly affect cancer metabolism. Smoking is the leading risk factor for non-small cell lung cancer (NSCLC). In this study, we identified that smoking modulates lung cancer cell metabolism through altered protein post-translational modification.

Knockdown of TIM3 Hampers Dendritic Cell Maturation and Induces Immune Suppression by Modulating T-Cell Responses.

Various inhibitors targeting T-cell immunoglobulin and mucin-containing molecule 3 (TIM3) aimed at reversing T-cell exhaustion for better immunotherapy outcomes have demonstrated limited clinical efficacy as monotherapy, with the underlying mechanisms remaining ambiguous. TIM3 is markedly expressed in dendritic cells (DCs), and the inconsistent research findings on its role in myeloid cells underscore its vital function within DCs. Through the establishment of an in vitro differentiation model generating mature dendritic cells (mDCs) under TIM3-targeted interventions, combined with an RNA sequencing analysis, this investigation systematically examined TIM3-mediated regulation and ligand interactions in human primary DCs.

LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1.

Background: Hepatocellular carcinoma (HCC) significantly affects the patient's physical and mental health. Long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been associated with the progression of HCC. However, the current effectiveness of HCC treatment is considered insufficient, and the scope of its therapeutic targets is highly limited.

Meplazumab, a CD147 antibody, for severe COVID-19: a double-blind, randomized, placebo-controlled, phase 3 clinical trial.

Meplazumab, a humanized CD147 antibody, showed favorable safety and clinical benefits in phase 1 and phase 2/3 seamless clinical studies. Further evaluation of its therapeutic efficacy in patients with severe COVID-19 is needed. In this phase 3 add-on study, we randomized patients with severe COVID-19 in a 1:1 ratio to receive 0.

Carnitine palmitoyltransferase 2 as a novel prognostic biomarker and immunoregulator in colorectal cancer.

Background: Metabolic interventions are critical for enhancing immunotherapy efficacy, but reliable metabolic targets remain absent for colorectal cancer (CRC). This study aims to investigate the interplay between metabolic and immunological factors in CRC, identify metabolic immunoregulatory molecules, and propose targets for prognostic and therapeutic applications.

Methods: Immune infiltration and metabolic pathways in CRC were analyzed using CIBERSORT and gene set variation analyses.

METTL3/IGF2BP3 mediates ORC6 via N6-methyladenosine modification to promote the progression of pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is recognized globally as one of the most lethal tumours, and effective biomarkers to diagnose PDAC early are needed. ORC6, a subunit of the origin recognition complex (ORC), initiates DNA replication and ensures genomic stability. Previous studies have indicated that ORC6 is procarcinogenic in various cancers, yet its role in PDAC remains uninvestigated.

Integrated Analysis of the Anoikis-Related Signature Identifies Rac Family Small GTPase 3 as a Novel Tumor-Promoter Gene in Hepatocellular Carcinoma.

Anoikis resistance in hepatocellular carcinoma (HCC) cells boosts survival and metastasis. This study aimed to establish an anoikis-related genes (ARGs)-based model for predicting HCC patients' outcomes and investigate the clinicopathological significance and function of crucial ARGs. The transcriptional expression patterns for HCC cohorts were compiled from TCGA, GEO and ICGC.

CD36 promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in earlystage hepatocellular carcinoma.

Background/aims: The identification of factors that lead to CD8+ T cell dysfunction within the tumor microenvironment (TME) holds great promise for the development of innovative immunotherapies. However, the mechanisms underlying the exhausted phenotype of CD8+ T cells infiltrating early-stage hepatocellular carcinoma (HCC) tumors remain unclear.

Methods: Single-cell RNA sequencing was performed using a murine HCC model.

Dicoumarol sensitizes hepatocellular carcinoma cells to ferroptosis induced by imidazole ketone erastin.

Introduction: Ferroptosis, an iron-dependent form of regulated cell death, is characterized by the lethal accumulation of lipid peroxides on cellular membranes. It not only inhibits tumor growth but also enhances immunotherapy responses and overcomes drug resistance in cancer therapy. The inhibition of the cystine-glutamate antiporter, system Xc-, induces ferroptosis.

An Anti-CD147 Antibody-Drug Conjugate Mehozumab-DM1 is Efficacious Against Hepatocellular Carcinoma in Cynomolgus Monkey.

Effective treatment strategies are urgently needed for hepatocellular carcinoma (HCC) patients due to frequent therapeutic resistance and recurrence. Antibody-drug conjugate (ADC) is a specific antibody-drug conjugated with small molecular compounds, which has potent killing activity against cancer cells. However, few ADC candidates for HCC are undergoing clinical evaluation.

Lower respiratory tract microbiome dysbiosis impairs clinical responses to immune checkpoint blockade in advanced non-small-cell lung cancer.

Background: Gut microbiome on predicting clinical responses to immune checkpoint inhibitors (ICIs) has been discussed in detail for decades, while microecological features of the lower respiratory tract within advanced non-small-cell lung cancer (NSCLC) are still relatively vague.

Methods: During this study, 26 bronchoalveolar lavage fluids (BALF) from advanced NSCLC participants who received immune checkpoint inhibitor monotherapy were performed 16S rRNA sequencing and untargeted metabolome sequencing to identify differentially abundant microbes and metabolic characteristics. Additionally, inflammatory cytokines and chemokines were also launched in paired BALF and serum samples by immunoassays to uncover their underlying correlations.

Spatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common histologic type of RCC. However, the spatial and functional heterogeneity of immunosuppressive cells and the mechanisms by which their interactions promote immunosuppression in the ccRCC have not been thoroughly investigated.

Methods: To further investigate the cellular and regional heterogeneity of ccRCC, we analyzed single-cell and spatial transcriptome RNA sequencing data from four patients, which were obtained from samples from multiple regions, including the tumor core, tumor-normal interface, and distal normal tissue.

Smad4 Deficiency in S100A4 Macrophages Enhances Colitis-associated Tumorigenesis by Promoting Macrophage Lipid Metabolism Augmented M2 Polarization.

S100A4 is primarily expressed in intestinal macrophages, and promotes colonic inflammation and colitis-associated colon tumorigenesis. Smad4 is also expressed in the colon; however, it inhibits colitis-associated cancer (CAC) development. The specific role of Smad4 in S100A4 cells in CAC remains unknown.

Revealing a cancer-associated fibroblast-based risk signature for pancreatic adenocarcinoma through single-cell and bulk RNA-seq analysis.

Purpose: Proliferation of stromal connective tissue is a hallmark of pancreatic adenocarcinoma (PAAD). The engagement of activated cancer-associated fibroblasts (CAFs) contributes to the progression of PAAD through their involvement in tumor fibrogenesis. However, the prognostic significance of CAF-based risk signature in PAAD has not been explored.

Skeletal muscle: molecular structure, myogenesis, biological functions, and diseases.

Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell-cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis.

Fragile Treg cells: Traitors in immune homeostasis?

Regulatory T (Treg) cells play a key role in maintaining immune tolerance and tissue homeostasis. However, in some disease microenvironments, Treg cells exhibit fragility, which manifests as preserved FoxP3 expression accompanied by inflammation and loss of immunosuppression. Fragile Treg cells are formatively, phenotypically and functionally diverse in various diseases, further complicating the role of Treg cells in the immunotherapeutic response and offering novel targets for disease treatment by modulating specific Treg subsets.

UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL.

Background/aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.

Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC.

CD147-K148me2-Driven Tumor Cell-Macrophage Crosstalk Provokes NSCLC Immunosuppression via the CCL5/CCR5 Axis.

Immunosuppression is a major hallmark of tumor progression in non-small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro-tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di-methylation in the immunosuppressive tumor microenvironment (TME) remains unclear.