Exon Skipping of Ste20-Like Kinase Enhances Glycolysis and Tumor Progression by Activating Enolase 1-Mediated Phosphoenolpyruvate Production.

RNA splicing is frequently dysregulated in tumors. Aberrant RNA splicing can alter tumor metabolism, highlighting the need to elucidate the alternative splicing events that shape the metabolic landscape. In this study, we identified exon skipping in Ste20-like kinase (SLK) that results in a variant isoform (SLKv), which promotes glycolysis in tumor cells.

Photo-induced hydrous organic aggregates for photoactivatable luminescence.

Harnessing light to regulate molecular aggregation behavior has become an essential approach to confer useful properties for functional materials at the aggregate level. Current examples of photo-induced aggregation predominantly occur in solution, but the solvent-ubiquitous as it is-is often overlooked as a potential participant in the aggregation process. In this study, photo-induced hydrous organic aggregates (HOA) are reported based on a hydrophobic nitroaromatic compound (NPAC).

Riplet promotes lipid metabolism changes associated with CD8 T cell exhaustion and anti-PD-1 resistance in hepatocellular carcinoma.

The overall response rate to immunotherapy is modest in hepatocellular carcinoma (HCC), and immunotherapy resistance mechanisms are incompletely understood. We report that the E3 ubiquitin ligase is universally silenced by promoter hypermethylation in HCC. Loss of modulates fatty acid metabolism to promote terminal exhaustion of CD8 T cells.

Single-Component High-Performance Adhesives Enabled by Synergistic Supramolecular and Covalent Polymerization.

The development of high-strength supramolecular adhesives from a single small molecule is a highly compelling research goal, as it offers the potential for lightweight, reversible, and stimuli-responsive bonding systems. However, achieving such adhesives presents significant challenges. Herein, we present a novel tripodal multifunctional molecule, , designed to exploit a synergistic supramolecular and covalent polymerization strategy to achieve a remarkable adhesive performance.

Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a challenging cancer with an increasing incidence. The Phase III TOPAZ-1/KEYNOTE-966 study demonstrated chemo-immunotherapy (CIT) as a significant advancement, potentially replacing traditional chemotherapy for advanced biliary tract cancer. Ferroptosis is a crucial process that affects cancer cell survival and therapy resistance.

Lone Pairs-Mediated Multiple Through-Space Interactions for Efficient Room-Temperature Phosphorescence.

The simultaneous generation and stabilization of triplet excitons are the key to realizing efficient organic room temperature phosphorescence (RTP), which is challenging owing to the obscure mechanism and structure-property relationships. Herein, a strategy of lone-pair-mediated multiple through-space interactions (TSIs) is proposed to availably induce RTP. By incorporating heteroatoms to facilitate through-space n-n and n-π interactions, the lone pairs are delocalized throughout the structure, resulting in the dense splitting of the excited-state energy levels.

Cancer stem cells and niches: challenges in immunotherapy resistance.

Cancer stem cells (CSCs) are central to tumor progression, metastasis, immune evasion, and therapeutic resistance. Characterized by remarkable self-renewal and adaptability, CSCs can transition dynamically between stem-like and differentiated states in response to external stimuli, a process termed "CSC plasticity." This adaptability underpins their resilience to therapies, including immune checkpoint inhibitors and adoptive cell therapies (ACT).

The larval gut of Spodoptera frugiperda harbours culturable bacteria with metabolic versatility after insecticide exposure.

Spodoptera frugiperda (fall armyworm) poses a substantial risk to crops worldwide, resulting in considerable economic damage. The gut microbiota of insects plays crucial roles in digestion, nutrition, immunity, growth and, sometimes, the degradation of insecticides. The current study examines the effect of synthetic insecticides on the gut microbiome of third instar S.

Prediction of Potential Habitat Distributions and Climate Change Impacts on the Rare Species (Magnoliaceae) in China Based on MaxEnt.

Changes in species' habitats provide important insights into the effects of climate change. , a critically endangered species endemic to karst ecosystems, has a highly restricted distribution and is a key biological resource. Despite its ecological importance, the factors influencing its habitat suitability and distribution remain poorly understood.

Intramolecular Repulsive Interactions Enable High Efficiency of NIR-II Aggregation-Induced Emission Luminogens for High-Contrast Glioblastoma Imaging.

Strategies to acquire high-efficiency luminogens that emit in the second near-infrared (NIR-II, 1000-1700 nm) range are still rare due to the impediment of the energy gap law. Herein, a feasible strategy is pioneered by installing large-volume encumbrances in a confined space to intensify the repulsive interactions arising from overlapping electron densities. The experimental results, including smaller coordinate displacement, reduced reorganization energy, and suppressed internal conversion, demonstrate that the repulsive interactions assist in the inhibition of radiationless deactivation.

Neuronal Tracing and Visualization of Nerve Injury by a Membrane-Anchoring Aggregation-Induced Emission Probe.

Deciphering neuronal circuits is pivotal for deepening our understanding of neuronal functions and advancing treatments for neurological disorders. Conventional neuronal tracers suffer from restrictions such as limited penetration depth, high immunogenicity, and inadequacy for long-term and imaging. In this context, we introduce an aggregation-induced emission luminogen (AIEgen), MeOTFVP, engineered for enhanced neuronal tracing and imaging.

Regulator of nonsense transcripts 3B is a prognostic biomarker and associated with immune cell infiltration in lung squamous cell and hepatocellular carcinoma.

Purpose: The characteristic of RENT3B in cancer remains ambiguous. We aimed to study the relationship between RENT3B and immune infiltration in liver hepatocellular carcinoma (LIHC) and lung squamous cell carcinoma (LUSC).

Patients And Methods: We investigated the expression levels of RENT3B using ONCOMINE and TIMER databases, and assessed the interrelationship between RENT3B expression and survival using PrognoScan, GEPIA, and Kaplan-Meier plotter.

Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2-mediated HMGB2 mRNA translation.

Background: N4-acetylcytidine (ac4C) represents a novel messenger RNA (mRNA) modification, and its associated acetyltransferase N-acetyltransferase 10 (NAT10) plays a crucial role in the initiation and progression of tumors by regulating mRNA functionality. However, its role in hepatocellular carcinoma (HCC) development and prognosis is largely unknown. This study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic approach.

CREB3 suppresses hepatocellular carcinoma progression by depressing AKT signaling through competitively binding with insulin receptor and transcriptionally activating RNA-binding motif protein 38.

cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood.

Room Temperature Phosphorescent Nanofiber Membranes by Bio-Fermentation.

Stimuli-responsive materials exhibiting exceptional room temperature phosphorescence (RTP) hold promise for emerging technologies. However, constructing such systems in a sustainable, scalable, and processable manner remains challenging. This work reports a bio-inspired strategy to develop RTP nanofiber materials using bacterial cellulose (BC) via bio-fermentation.

TGF-β downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial-mesenchymal transition of liver progenitor cells.

Background: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances.

Results: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-β promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-β activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFβ-Smad signaling induced growth inhibition and partial EMT, whereas TGFβ-MAPK signaling had the opposite effects on LPCs.

A pair of primary colorectal cancer-derived and corresponding synchronous liver metastasis-derived organoid cell lines.

Proper preclinical models for the research of colorectal cancer (CRC) and CRC liver metastases (CLM) are a clear and unmet need. Patient-derived organoids have recently emerged as a robust preclinical model, but are not available to all scientific researchers. Here, we present paired 3D organoid cell lines of CWH22 (CRC-derived) and CLM22 (CLM-derived) with sound background information and the short tandem repeats are identical to those of the normal tissue.

YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD-L1/VEGFA Axis.

N6-methyladenosine (mA) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion and angiogenesis are characteristic features of its TME. The role of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), as an mA reader, in regulating HCC TME are not fully understood.

Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8 T cell-mediated antitumour immunity and improves anti-PD-1 efficacy.

Objective: The gain of function (GOF) CTNNB1 mutations (CTNNB1 ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC.

Design: RNA sequencing was performed to identify the key downstream genes of CTNNB1 associated with immune escape.

Remarkable Off-On Tunable Solid-State Luminescence by the Regulation of Pyrene Dimer.

It is always a challenge to achieve "off-on" luminescent switch by regulating non-covalent interactions. Herein, we report a unique strategy for constructing high performance "off-on" tunable luminescent materials utilizing a novel molecule (TFPA) consist of pyrene and cyanostilbene. The pristine crystal of TFPA is almost non-emissive.