Au-incorporated metal-organic frameworks nanozymes for thioreduction and glutathione depletion-mediated efficient photoimmunotherapy.

Tumor therapy has historically been a global research focus, with phototherapy garnered significant attention as a innovative treatment modality. However, the antioxidant defense system in the tumor microenvironment, characterized by excessive glutathione (GSH) and thiol-containing proteins, often limits the effectiveness of photodynamic therapy. In this study, we report the development of a new multifunctional integrated nanozyme with thioredoxin reductase-oxidase (TrxRox) and GSH-oxidase (GSHox)-like activities.

Pan-cancer characterization of cellular senescence reveals its inter-tumor heterogeneity associated with the tumor microenvironment and prognosis.

Cellular senescence (CS) is characterized by the irreversible cell cycle arrest and plays a key role in aging and diseases, such as cancer. Recent years have witnessed the burgeoning exploration of the intricate relationship between CS and cancer, with CS recognized as either a suppressing or promoting factor and officially acknowledged as one of the 14 cancer hallmarks. However, a comprehensive characterization remains absent from elucidating the divergences of this relationship across different cancer types and its involvement in the multi-facets of tumor development.

Tumor suppressor BAP1 suppresses disulfidptosis through the regulation of SLC7A11 and NADPH levels.

BAP1, BRCA1-Associated Protein 1, serves as a novel tumor suppressor through the deubiquitination of monoubiquitination of H2A and subsequent gene transcriptional regulation. Regulated cell death like apoptosis or ferroptosis is considered an essential mechanism mediating tumor suppression. Previous reports, including ours, have demonstrated that BAP1 could promote apoptosis and ferroptosis to inhibit tumor development.

Nanoreactors with Cascade Catalytic Activity Reprogram the Tumor Microenvironment for Enhanced Immunotherapy by Synchronously Regulating Treg and Macrophage Cells.

Immunotherapy has been extensively utilized and studied as a prominent therapeutic strategy for tumors. However, the presence of a hypoxic immunosuppressive tumor microenvironment significantly reduces the efficacy of the treatment, thus impeding its application. In addition, the hypoxic microenvironment can also lead to the enrichment of immunosuppressive cells and reduce the effectiveness of tumor immunotherapy; nanoparticles with biocatalytic activity have the ability to relieve hypoxia in tumor tissues and deliver drugs to target cells and have been widely concerned and applied in the field of tumor therapy.

LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism.

LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner.

FAM188B promotes the growth, metastasis, and invasion of hepatocellular carcinoma by targeting the hnRNPA1/PKM2 axis.

Hepatocellular carcinoma (HCC), the leading cause of cancer-related deaths worldwide, is characterised by rapid growth and marked invasiveness. Accumulating evidence suggests that deubiquitinases play a pivotal role in HCC growth and metastasis. However, the expression of the deubiquitinase FAM188B and its biological functions in HCC remain unknown.

OTUD5 promotes the growth of hepatocellular carcinoma by deubiquitinating and stabilizing SLC38A1.

Background: Deubiquitinating enzymes (DUBs) cleave ubiquitin on substrate molecules to maintain protein stability. DUBs reportedly participate in the tumorigenesis and tumour progression of hepatocellular carcinoma (HCC). OTU deubiquitinase 5 (OTUD5), a DUB family member, has been recognized as a critical regulator in bladder cancer, breast cancer and HCC.

USP40 promotes hepatocellular carcinoma progression through a YAP/USP40 positive feedback loop.

Yes-associated protein (YAP) is an essential driver of hepatocellular carcinoma (HCC) progression and the ubiquitin-proteasome system controls its abundance. However, the role of ubiquitin-specific protease 40 (USP40) in YAP stability remains unclear. Here, USP40 was first identified as a novel regulator of YAP abundance and its target genes in HCC cells.

USP40 promotes hepatocellular carcinoma cell proliferation, migration and stemness by deubiquitinating and stabilizing Claudin1.

Background: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a major threat to people's lives and health. Previous studies have found that multiple deubiquitinating enzymes are involved in the pathogenesis of HCC. The purpose of this work was to elucidate the function and mechanism of the deubiquitinating enzyme USP40 in HCC progression.

Carbon dot nanozymes as free radicals scavengers for the management of hepatic ischemia-reperfusion injury by regulating the liver inflammatory network and inhibiting apoptosis.

Background: Hepatic ischemia-reperfusion injury (HIRI) is a pathophysiological process during liver transplantation, characterized by insufficient oxygen supply and subsequent restoration of blood flow leading to an overproduction of reactive oxygen species (ROS), which in turn activates the inflammatory response and leads to cellular damage. Therefore, reducing excess ROS production in the hepatic microenvironment would provide an effective way to mitigate oxidative stress injury and apoptosis during HIRI. Nanozymes with outstanding free radical scavenging activities have aroused great interest and enthusiasm in oxidative stress treatment.

FOXC2-AS1/FOXC2 axis mediates matrix stiffness-induced trans-differentiation of hepatic stellate cells into fibrosis-promoting myofibroblasts.

Matrix stiffness is a central modulator of hepatic stellate cells (HSCs) activation and hepatic fibrogenesis. However, the long non-coding RNAs (lncRNAs)-regulated transcriptional factors linking matrix stiffness to alterations in HSCs phenotype are not completely understood. In this study, we investigated the effects of matrix stiffness on HSCs activation and its potential mechanism.

The regulation of amino acid metabolism in tumor cell death: from the perspective of physiological functions.

Amino acids (AAs) are crucial molecules for the synthesis of mammalian proteins as well as a source of energy and redox equilibrium maintenance. The development of tumors also requires AAs as nutrients. Increased AAs metabolism is frequently seen in tumor cells to produce enough biomass, energy, and reduction agents.

[Corrigendum] MicroRNA‑92a contributes to tumor growth of human hepatocellular carcinoma by targeting FBXW7.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that certain of the control western blotting data featured in Fig. 5 on p. 2581 had also appeared in a couple of other articles featuring several of the same authors [Tu K, Dou C, Zheng X, Li C, Yang W, Yao Y and Liu Q: Fibulin‑5 inhibits hepatocellular carcinoma cell migration and invasion by down‑regulating matrix metalloproteinase‑7 expression.

Confined Cascade Metabolic Reprogramming Nanoreactor for Targeted Alcohol Detoxification and Alcoholic Liver Injury Management.

Alcoholic liver injury (ALI) is the leading cause of serious liver disease, whereas current treatments are mostly supportive and unable to metabolize alcohol directly. Here we report a metabolic reprogramming strategy for targeted alcohol detoxification and ALI management based on a confined cascade nanoreactor. The nanoreactor (named AA@mMOF) is designed by assembling natural enzymes of alcohol oxidase (AOx) and aldehyde dehydrogenase (ALDH) in the cavity of a mesoporous metal organic framework (mMOF) nanozyme with intrinsic catalase (CAT)-like activity.

HIF-1α-activated TMEM237 promotes hepatocellular carcinoma progression via the NPHP1/Pyk2/ERK pathway.

Background: Hypoxia-inducible factors (HIFs) are the most essential endogenous transcription factors in the hypoxic microenvironment and regulate multiple genes involved in the proliferation, migration, invasion, and EMT of hepatocellular carcinoma (HCC) cells. However, the regulatory mechanism of HIFs in driving HCC progression remains poorly understood.

Methods: Gain- and loss-of-function experiments were carried out to investigate the role of TMEM237 in vitro and in vivo.

Reactive oxygen species-responsive nanocarrier ameliorates murine colitis by intervening colonic innate and adaptive immune responses.

Ulcerative colitis (UC) is a chronic or relapsing inflammatory disease with limited therapeutic outcomes. Pterostilbene (PSB) is a polyphenol-based anti-oxidant that has received extensive interest for its intrinsic anti-inflammatory and anti-oxidative activities. This work aims to develop a reactive oxygen species (ROS)-responsive, folic acid (FA)-functionalized nanoparticle (NP) for efficient PSB delivery to treat UC.

Erratum: Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of hepatocellular carcinoma: Erratum.

[This corrects the article DOI: 10.7150/thno.26789.

Orally administration of cerium oxide nanozyme for computed tomography imaging and anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) is a chronic nonspecific disease with unknown etiology. Currently, the anti-inflammatory therapeutic approaches have achieved a certain extent of effects in terms of inflammation alleviation. Still, the final pathological outcome of intestinal fibrosis has not been effectively improved yet.

Deciphering the catalytic mechanism of superoxide dismutase activity of carbon dot nanozyme.

Nanozymes with superoxide dismutase (SOD)-like activity have attracted increasing interest due to their ability to scavenge superoxide anion, the origin of most reactive oxygen species in vivo. However, SOD nanozymes reported thus far have yet to approach the activity of natural enzymes. Here, we report a carbon dot (C-dot) SOD nanozyme with a catalytic activity of over 10,000 U/mg, comparable to that of natural enzymes.

Comprehensive analysis of the amino acid metabolism-related gene signature for prognosis, tumor immune microenvironment, and candidate drugs in hepatocellular carcinoma.

Introduction: Metabolic rewiring satisfies increased nutritional demands and modulates many oncogenic processes in tumors. Amino acid metabolism is abnormal in many malignancies. Metabolic reprogramming of amino acids not only plays a crucial role in sustaining tumor cell proliferation but also influences the tumor immune microenvironment.

[Corrigendum] BCL‑3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1.

Subsequently to the publication of the above article, the authors have alerted the Editorial Office to the fact that they identified a small number of errors concerning the assembly of Figs. 3A, 6B and 7A in their paper. Specifically, the western blotting results for the BCL‑3 and GAPDH experiments in Fig.

Decoy Nanozymes Enable Multitarget Blockade of Proinflammatory Cascades for the Treatment of Multi-Drug-Resistant Bacterial Sepsis.

Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection. Effective treatment of bacterial sepsis remains a paramount clinical challenge, due to its astonishingly rapid progression and the prevalence of bacterial drug resistance. Here, we present a decoy nanozyme-enabled intervention strategy for multitarget blockade of proinflammatory cascades to treat multi-drug-resistant (MDR) bacterial sepsis.