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Sorafenib is widely used in treating advanced hepatocellular carcinoma (HCC). However, its effectiveness in prolonging patient survival is limited by the development of drug resistance. To systematically investigate the resistance mechanisms of Sorafenib, an integrative analysis combining posttranslational modification (PTM) omics and CRISPR/Cas9 knockout library screening was conducted. This analysis identified ubiquitination at lysine 21 (K21) on chaperonin-containing TCP1 subunit 3 (CCT3) as being associated with Sorafenib resistance. Transcriptomic data from HCC patients treated with Sorafenib revealed that CCT3 expression was lower in responders compared to non-responders. Experimentally, inhibiting the expression of CCT3 sensitized HCC cells to Sorafenib and enhanced Sorafenib-induced ferroptosis. Additionally, CCT3 was found to interact with ACTN4, hindering the recycling of transferrin receptor protein 1 (TFRC) to the cell membrane, thus obstructing iron endocytosis. Mechanistically, the inhibition of ferroptosis by CCT3 depends on the deubiquitination of K6-linked non-degradative ubiquitination at its K21, which occurs upon Sorafenib treatment. Moreover, CCT3 knockdown enhanced the anti-tumor effects of Sorafenib in nude mice. In summary, we have identified a novel function of the chaperone protein. Targeting the CCT3/ACTN4/TFRC axis offers a promising strategy to enhance ferroptosis and overcome Sorafenib resistance in HCC. [ABSTRACT FROM AUTHOR]

Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular signaling. The liver is a crucial site for BCAA metabolism, linking the changes in BCAA homeostasis with the pathogenesis of a variety of liver diseases and their complications. Peripheral circulating BCAA levels show complex trends in different liver diseases. This review delineates the alterations of BCAAs in conditions including non-alcoholic fatty liver disease, hepatocellular carcinoma, cirrhosis, hepatic encephalopathy, hepatitis C virus infection, and acute liver failure, as well as the potential mechanisms underlying these changes. A significant amount of clinical research has utilized BCAA supplements in the treatment of patients with cirrhosis and liver cancer. However, the efficacy of BCAA supplementation in clinical practice remains uncertain and controversial due to the heterogeneity of studies. This review delves into the complicated relationship between BCAAs and liver diseases and tries to untangle what role BCAAs play in the occurrence, development, and outcomes of liver diseases. [ABSTRACT FROM AUTHOR]

Cancer is a serious threat to human life. However, the effect of single treatment method is limited at present. Here, a Cu2SnTe3 (CST) nano‐reagent which can provide a strong synergetic effect in tumor therapy is successfully constructed. CST nanoparticles can not only convert endogenous H2O2 into ∙OH through surface‐catalyzed reactions, but also generate 1O2 based on light irradiation‐induced electron pair separation, leading to excessive oxidative stress accumulation in tumor cells. Interestingly, CST nanoparticles are also found to possess catalase‐like activity, which enhances the level of O2 within hypoxic tumors, further improving the production efficiency of 1O2 by photodynamic therapy (PDT). In addition, the CST nanoparticles exhibit good photothermal conversion, which facilitates to promote more ∙OH production by chemodynamic therapy (CDT). The results of in vitro and in vivo anti‐tumor experiments both demonstrate that CST nanoparticles can effectively inhibit the growth of tumor with minimal side effects. To sum up, CST nanoparticles have great potential in tumor treatment for efficient synergetic CDT/PDT/photothermal therapy. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Longitudinal dynamic single-cell mass cytometry analysis of peripheral blood mononuclear cells in COVID-19 patients within 6 months after viral RNA clearance." The correction involves updating the first affiliation of the authors to the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, in Hangzhou, China. The original article has been corrected, and the publisher remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Lithium (Li) metal batteries are highly sought after for their exceptional energy density. However, their practical implementation is impeded by the formation of dendrites and significant volume fluctuations in Li, which stem from the uneven distribution of Li-ions and uncontrolled deposition of Li on the current collector. Here, an amino-functionalized reduced graphene oxide covered with polyacrylonitrile (PrGN) film with an electric field gradient structure is prepared to deal with such difficulties. This novel current collector serves to stabilize Li-metal anodes by regulating Li-ion flux through vertically aligned channels formed by porous polyacrylonitrile (PAN). Moreover, the amino-functionalized reduced graphene oxide (rGN) acts as a three-dimensional (3D) host, reducing nucleation overpotential and accommodating volume expansion during cycling. The combination of the insulating PAN and conducting rGN creates an electric field gradient that promotes a bottom-up mode of Li electrodeposition and safeguards the anode from interfacial parasitic reactions. Consequently, the electrodes exhibit exceptional cycle life with stable voltage profiles and minimal hysteresis under high current densities and large areal capacities., (© 2023 Wiley-VCH GmbH.)

Background: Acute-on-chronic liver failure (ACLF) is an acute decompensated syndrome based on chronic liver disease, while neutrophil recruitment is the most critical early step. C-X-C motif chemokine ligand 1 (CXCL1), a cytokine that recruits neutrophils, was significantly upregulated in both ACLF mice and patients with ACLF. This present study aims to explore the role of CXCL1 in the pathogenesis of ACLF., Methods: We established an ACLF mouse model induced by carbon tetrachloride, lipopolysaccharide, and D-galactosamine, and used adeno-associated virus to achieve overexpression and knockdown of Cxcl1. We employed mass cytometry, flow cytometry, multiplex cytokine and chemokine analysis, Western blot, and reactive oxygen species (ROS) detection in mice blood and liver. ACLF patients (n = 10) and healthy controls (n = 5) were included, and their liver samples were stained using multiplex immunohistochemistry techniques., Results: CXCL1 was significantly elevated in both ACLF mice and patients. CXCL1 recruits neutrophils by binding to the C-X-C motif chemokine receptor 2 on the surface of neutrophils, affects ACLF prognosis by generating ROS and mitochondrial depolarization and modulating caspase3-related apoptotic pathways. We found that the knockdown of CXCL1 attenuated the infiltration of neutrophils in the mouse liver, reduced the expression of inflammatory cytokines, and also significantly downregulated ROS production and caspase3-related hepatocyte apoptosis, thereby ameliorating the liver injury of ACLF., Conclusions: CXCL1 is a core player in the mobilization of neutrophils in ACLF, and the knockdown of Cxcl1 improves neutrophil infiltration, reduces ROS levels, and reduces hepatocyte apoptosis, thereby attenuating inflammation and liver injury in ACLF. Our results revealed a previously unknown link between CXCL1-induced neutrophil recruitment and ACLF, providing evidencing for potential therapies targeting ACLF., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)