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High‐mobility group box 1 (HMGB1) was initially recognized as a ubiquitous nuclear protein involved in maintaining the nucleosome integrity and facilitating gene transcription. HMGB1 has since been reevaluated to be a prototypical damage‐associated molecular pattern (DAMP) protein, and together with its exogenous counterpart, pathogen‐associated molecular pattern (PAMP), completes the body's alarmin system against disturbances in homeostasis. HMGB1 can be released into the extracellular matrix (ECM) by either granulocytes or necrotic cells to serve as a chemotaxis/cytokine during infection, endotoxemia, hypoxia, ischemia–reperfusion events, and cancer. Different isoforms of HMGB1 present with distinctive physiological functions in ECM—fully‐reduced HMGB1 (all thiol) acts as the initial damage signal to recruit circulating myeloid cells, disulfide HMGB1 behaves as a cytokine to activate macrophages and neutrophils, and both signals are turned off when HMGB1 is terminally oxidized into the final sulfonate form. Targeting HMGB1 constitutes a favorable therapeutic strategy for inflammation and inflammatory diseases. Antagonists such as ethyl pyruvate inhibit HMGB1 by interfering with its cytoplasmic exportation, while others such as glycyrrhizin directly bind to HMGB1 and render it unavailable for its receptors. The fact that a mixture of different HMGB1 isoforms is present in the ECM poses a challenge in pinpointing the exact role of an individual antagonist. A more discriminative probe for HMGB1 may be necessary to advance our knowledge of HMGB1, HMGB1 antagonists, and inflammatory‐related diseases. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan‐histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy. Methods: Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin‐peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis‐free survival/post‐brain metastatic survival were evaluated using Kaplan‐Meier curves and Cox regression analyses. Results: HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis‐free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post‐brain metastasis. Conclusions: Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine. Key points: Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis‐free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated. [ABSTRACT FROM AUTHOR]

N,W codoped TiO 2 $\mathrm{TiO}_{2}$ nanorods were synthesized via a one-step hydrothermal method using ammonium metatungstate as the nitrogen and tungstate sources. The prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV–visible diffuse reflectance spectroscopy (DRS), and X-ray photoelectron spectroscopy (XPS). The results indicated that the N,W codoped TiO 2 $\mathrm{TiO}_{2}$ nanorods exhibited a higher photocatalytic activity under visible light irradiation compared with P25 and undoped TiO 2 $\mathrm{TiO}_{2}$ , because the codoping of N and W ions not only extended the visible light absorption but also promoted the separation of the photogenerated electrons and holes. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has demonstrated that N6-methyladenosine (m 6 A) plays important roles in a variety of diseases. However, the specific functions of m 6 A in CdCl 2 -induced kidney injury remain unclear., Objective: Here, we investigate a transcriptome-wide map of m 6 A modifications and explore the effects of m 6 A on Cd-induced kidney injury., Materials and Methods: The rat kidney injury model was constructed by subcutaneous injection of CdCl 2 (0.5, 1.0, and 2.0 mg/kg). The m 6 A levels were measured by colorimetry. The level of expression of m 6 A-related enzymes were detected by reverse transcription quantitative real-time PCR analysis. Transcriptome-wide m 6 A methylome in CdCl 2 (2.0 mg/kg) and the control group were profiled by methylated RNA immunoprecipitation sequencing (MeRIP-seq). Subsequently, the sequencing data were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), while gene set enrichment analysis (GSEA) confirmed the functional enrichment pathways of sequencing genes. In addition, a protein-protein interaction (PPI) network was applied to select hub genes., Results: The levels of m 6 A and m 6 A regulators (METTL3, METTL14, WTAP, YTHDF2) were significantly increased in CdCl 2 groups. We identified a total of 2615 differentially expressed m 6 A peaks, 868 differentially expressed genes and 200 genes with significant changes in both m 6 A modification and gene expression levels. GO, KEGG, and GSEA analyses indicated that these genes were mainly enriched in inflammation and metabolism-related pathways such as in IL-17 signaling and fatty acid metabolism. According the result of the conjoint analysis, we identified the top ten hub genes (Fos, Hsp90aa1, Gata3, Fcer1g, Cftr, Cspg4, Atf3, Cdkn1a, Ptgs2, and Npy) which may be regulated by m 6 A and involve in CdCl 2 -induced kidney damage., Conclusion: This study established a m 6 A transcriptional map in a CdCl 2 -induced kidney injury model and suggested that m 6 A may affect CdCl 2 induced kidney injury via regulated the inflammation and metabolism related gene., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Colorectal cancer (CRC) has become a predominant cancer and accounts for approximately 10% of cancer-related mortality. Drug resistance still remains a priority mortality factor for patients due to no available therapeutic alternatives. The purpose of the present study was to investigate the underlying molecular mechanisms how eukaryotic translation initiation factor 3 subunit G (EIF3G) resensitized 5-Fu-resistant human CRC cells (HCT116/5-Fu) to 5-fluorouracil (5-Fu)., Methods: Multiple cellular and molecular biology experiments were performed in the present study, such as CCK-8, western blotting and flow cytometry., Results: We found that EIF3G is highly expressed at RNA and protein levels in HCT116/5-Fu cells compared with HCT116 cells using quantitative real-time polymerase chain reaction and Western blot analysis. In addition, silencing EIF3G enhanced 5-Fu-induced apoptosis in HCT116/5-Fu cells. Moreover, EIF3G silencing decreased the activity of the drug-related proteins MDR1 and MRP levels in HCT116/5-Fu cells. Finally, the xenograft tumor model further confirmed that EIF3G resensitized HCT116/5-Fu tumors to 5-Fu. We observed that EIF3G silencing followed by 5-Fu administration had a synergistic interaction effect on HCT116/5-Fu in vitro and in vivo., Conclusion: These findings demonstrate that EIF3G is a targetable regulator of chemoresistance in CRC, and inhibiting EIF3G in combination with 5-Fu might be a potential therapeutic strategy for colon cancer., Competing Interests: Disclosure The authors report no conflicts of interest in this work.