TCF25 serves as a nutrient sensor to orchestrate metabolic adaptation and cell death by enhancing lysosomal acidification under glucose starvation.

Cells adapt to nutrient limitation by activating catabolic and inhibiting anabolic pathways, yet prolonged stress may lead to cell death. How cells orchestrate metabolic adaptation and cell death to nutrient stress is poorly understood. We conduct a genome-wide CRISPR-Cas9 screen to identify regulators in glucose-starvation-induced cell death and find a group of genes in lysosomal pathway is enriched following glucose starvation.

Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadliest forms of liver cancer worldwide. Despite advances in treatment, the prognosis for HCC patients remains poor due to the complex interplay of genetic, environmental, and immunological factors driving its progression. Understanding the immune landscape of HCC is crucial for developing effective therapies, particularly in the field of immunotherapy, which holds great promises for improving patient outcomes.

AI-driven eyelid tumor classification in ocular oncology using proteomic data.

Eyelid tumors pose diagnostic challenges due to their diverse pathological types and limited biopsy materials. This study aimed to develop an artificial intelligence (AI) diagnostic system for accurate classification of eyelid tumors. Utilizing mass spectrometry-based proteomics, we analyzed proteomic data from eight tissue types and identified eighteen novel biomarkers based on 233 formalin-fixed, paraffin-embedded (FFPE) samples from 150 patients.

Identification of KW-2449 as a dual inhibitor of ferroptosis and necroptosis reveals that autophagy is a targetable pathway for necroptosis inhibitors to prevent ferroptosis.

Necroptosis and ferroptosis are two distinct forms of necrotic-like cell death in terms of their morphological features and regulatory mechanisms. These two types of cell death can coexist in disease and contribute to pathological processes. Inhibition of both necroptosis and ferroptosis has been shown to enhance therapeutic effects in treating complex necrosis-related diseases.

Effect of different genetic backgrounds on rumen microbiota and serum metabolic phenotypes in beef cattle.

Species with different genetic backgrounds exhibit distinct metabolic traits. Nine beef cattle were selected for the experiment to study changes in serum metabolic phenotypes, rumen microbiota diversity, and composition in beef cattle from different genetic backgrounds. Three groups were Chinese Simmental (S group), Simmental×Chinese Holstein (SH group), and Simmental × Mongolian (SM group) cattle.

Identification of a marine-derived sesquiterpenoid, Compound-8, that inhibits tumour necrosis factor-induced cell death by blocking complex II assembly.

Background And Purpose: Tumour necrosis factor (TNF) is a pleiotropic inflammatory cytokine that not only directly induces inflammatory gene expression but also triggers apoptotic and necroptotic cell death, which leads to tissue damage and indirectly exacerbates inflammation. Thus, identification of inhibitors for TNF-induced cell death has broad therapeutic relevance for TNF-related inflammatory diseases. In the present study, we isolated and identified a marine fungus-derived sesquiterpenoid, 9α,14-dihydroxy-6β-p-nitrobenzoylcinnamolide (named as Cpd-8), that inhibits TNF receptor superfamily-induced cell death by preventing the formation of cytosolic death complex II.

Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis.

Ulcerative colitis is a chronic inflammatory bowel disorder with cellular heterogeneity. To understand the composition and spatial changes of the ulcerative colitis ecosystem, here we use imaging mass cytometry and single-cell RNA sequencing to depict the single-cell landscape of the human colon ecosystem. We find tissue topological changes featured with macrophage disappearance reaction in the ulcerative colitis region, occurring only for tissue-resident macrophages.

Multi-omics analysis reveals the chemoresistance mechanism of proliferating tissue-resident macrophages in PDAC via metabolic adaptation.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer that typically demonstrates resistance to chemotherapy. Tumor-associated macrophages (TAMs) are essential in tumor microenvironment (TME) regulation, including promoting chemoresistance. However, the specific TAM subset and mechanisms behind this promotion remain unclear.

Systemic inflammation influences the prognosis of patients with radically resected non-small cell lung cancer and correlates with the immunosuppressive microenvironment.

The impact of host condition on prognosis of non-small cell lung cancer (NSCLC) and the interaction between host and NSCLC remain unclear. This study investigated the association between systemic inflammation and prognosis and characteristics of radically resected NSCLC. This study consisted of a cohort study and an exploratory study of institutional prospective databases.

Demethyleneberberine alleviated the inflammatory response by targeting MD-2 to inhibit the TLR4 signaling.

Introduction: The colitis induced by trinitrobenzenesulfonic acid (TNBS) is a chronic and systemic inflammatory disease that leads to intestinal barrier dysfunction and autoimmunedisorders. However, the existing treatments of colitis are associated with poor outcomes, and the current strategies remain deep and long-time remission and the prevention of complications. Recently, demethyleneberberine (DMB) has been reported to be a potential candidate for the treatment of inflammatory response that relied on multiple pharmacological activities, including anti-oxidation and antiinflammation.

Effects of regel essential oil supplementation on growth performance, nutrient digestibility, rumen fermentation, and bacterial communities in sheep.

The objectives of this research were to investigate the effects of Regel essential oil on growth performance, nutrient digestibility, rumen fermentation, and bacterial communities in sheep Twenty sheep were randomly divided into two dietary groups with 10 replicates each: (1) a basal diet without AMO as the control group ( = 10) and (2) a basal diet supplemented with 40 mg/kg AMO as the AMO group ( = 10). The average daily gain (ADG) was increased ( < 0.05), and the feed conversion ratio (FCR) was reduced ( < 0.

Demethyleneberberine blocked the maturation of IL-1β in inflammation by inhibiting TLR4-mitochondria signaling.

Demethyleneberberine (DMB) is a natural product from traditional Chinese medicinal herb the rhizome of Coptis chinensis Franch., which has been reported to possess multiple pharmacological activities, especially anti-inflammation and immunoregulation. However, the potential mechanism of DMB in inflammation is still a mystery.

Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma.

Rationale: Hypoxia in tumor microenvironment (TME) represents an obstacle to the efficacy of immunotherapy for pancreatic ductal adenocarcinoma (PDAC) through several aspects such as increasing the expression of immune checkpoints or promoting fibrosis. Reversing hypoxic TME is a potential strategy to improve the validity of immune checkpoint blockade (ICB).

Methods: Here, we synthesized polydopamine-nanoparticle-stabilized oxygen microcapsules with excellent stabilization, bioavailability, and biocompatibility for direct oxygen delivery into tumor sites by interfacial polymerization.

Recent Advancements of Nanotechnology-Based Strategies for Overcoming Tumor Microenvironment Hypoxia.

Hypoxia is a typical characteristic of most solid malignancies, which has multiple effects on malignant phenotypes and biological behaviors of tumors including epithelial-mesenchymal-transition (EMT), invasion, migration, metastasis, autophagy, stem cell maintenance, pathological angiogenesis, drug resistance, and immunosuppression. Rcentlyumoand reversing the tumor hypoxic environment via nanotechnology has emerged as a novel therapeutic approach for the treatment of malignancies. The main strategies related to nanotechnology to alleviate or ameliorate hypoxic environment are as follows: (1) Bringing external oxygen to tumor hypoxic microenvironment; (2) Generating oxygen based on nanotechnology ; (3) Regulating the structure of the tumor microenvironment; (4) Decreasing oxygen consumption in the tumor microenvironment.

Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny.

Objective: Hepatocellular carcinoma (HCC) tumour microenvironment (TME) is highly complex with diverse cellular components organising into various functional units, cellular neighbourhoods (CNs). And we wanted to define CN of HCC while preserving the TME architecture, based on which, potential targets for novel immunotherapy could be identified.

Design: A highly multiplexed imaging mass cytometry (IMC) panel was designed to simultaneously quantify 36 biomarkers of tissues from 134 patients with HCC and 7 healthy donors to generate 562 highly multiplexed histology images at single-cell resolution.

How to do quantile normalization correctly for gene expression data analyses.

Quantile normalization is an important normalization technique commonly used in high-dimensional data analysis. However, it is susceptible to class-effect proportion effects (the proportion of class-correlated variables in a dataset) and batch effects (the presence of potentially confounding technical variation) when applied blindly on whole data sets, resulting in higher false-positive and false-negative rates. We evaluate five strategies for performing quantile normalization, and demonstrate that good performance in terms of batch-effect correction and statistical feature selection can be readily achieved by first splitting data by sample class-labels before performing quantile normalization independently on each split ("Class-specific").

Gegen Qinlian decoction maintains colonic mucosal homeostasis in acute/chronic ulcerative colitis via bidirectionally modulating dysregulated Notch signaling.

Background: Gegen Qinlian decoction (GQ) is a well-known traditional Chinese medicine that has been clinically proven to be effective in treating ulcerative colitis (UC). However, its therapeutic mechanism has not been fully elucidated. Notch signaling plays an essential role in the regeneration of the intestinal epithelium.

Demethyleneberberine attenuates concanavalin A-induced autoimmune hepatitis in mice through inhibition of NF-κB and MAPK signaling.

Demethyleneberberine (DMB) is a natural product which has been reported to possess mitochondria-targeting anti-oxidative and anti-inflammatory effect. However, the pharmacological action and molecular mechanism of DMB on autoimmune hepatitis (AIH) have not been explored. In this study, AIH was induced by intravenously injecting Con A (20 mg/kg) in mice for 8 h, and DMB protected against Con A-induced AIH, evidenced by obvious reduction of hepatic enzymes in serum and histological lesion.