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The virulence of SARS-CoV-2 decreases with increasing infectivity, the primary approaches for antiviral treatments will be preventing or minimizing the complications resulting from virus infection. ADAM metallopeptidase domain 17 (ADAM17) activation by SARS-CoV-2 infection has a dual effect on the development of the disease: increased release of inflammatory cytokines and dysregulation of Angiotensin converting enzyme II (ACE2) on cell surfaces, inflammatory cytokine infiltration and loss of ACE2 protective function lead to a significant increase in the incidence of related complications. Importantly, pathologically activated ADAM17 showed superior features than S protein in regulating ACE2 expression and participating in the intra cellular replication of SARS-CoV-2. In short, SARS-CoV-2 elicits only a limited immune response when it promotes its own replication and pathogenicity through ADAM17. Therefore, the pathological activation of ADAM17 may also represent a diminished innate antiviral defense and an altered strategy of SARS-CoV-2 infection. In this review, we summarized recent advances in our understanding of the pathophysiology of ADAM17, with a focus on the new findings that SARS-CoV-2 affects ADAM17 expression through Furin protein converting enzyme and Mitogen-activated protein kinase (MAPK) pathway, and raises the hypothesis that SARS-CoV-2 may mediates the pathological activation of ADAM17 by hijacking the actin regulatory pathway, and discussed the underlying biological principles. • The complications induced by SARS-CoV-2 infection are related to pathological activation of ADAM17 • The mechanism of pathological activation of ADAM17 by SARS-CoV-2 remains unclear • The role of actin cytoskeleton in SARS-CoV-2 infection was hypothesized [ABSTRACT FROM AUTHOR]

Poor sensitivity to sorafenib has been an important constraint on the efficacy of targeted therapy in advanced hepatocellular carcinoma (HCC). Therefore, it is particularly important to explore effective therapeutic targets to improve the sensitivity of HCC cells to sorafenib. Upregulation of IGF2BP3 is strongly associated with tumor invasion, early recurrence and poor prognosis in various human cancers, including HCC, but its roles in the sorafenib treatment of HCC remain unclear. In our study, IGF2BP3 knock-down significantly promoted ferroptosis in HCC cells through the evaluation of the Reactive Oxygen Species (ROS), Fe2+ and malondialdehyde (MDA) levels after sorafenib administration. In addition, NRF2 mRNA was identified as an important target of IGF2BP3 by bioinformatics analysis, RNA binding protein immunoprecipitation (RIP) and RNA pulldown experiments. More importantly, IGF2BP3, as an m6A (N6-Methyladenosine) reader, was shown to promote the stability of NRF2 mRNA by reading its m6A modification. Similar results were obtained from in vivo experiments. In summary, our study uncovered the role of IGF2BP3- NRF2 axis on ferroptosis in HCC, providing significant evidence for new anti-cancer strategies aimed at improving the efficacy of sorafenib. • IGF2BP3 negatively regulates sorafenib-induced ferroptosis in HCC cells. • IGF2BP3 can bind to the mRNA of NRF2. • IGF2BP3 inhibits ferroptosis by stabilizing NRF2 mRNA in an m6A-dependent manner. • IGF2BP3 knock-down improves the efficacy of sorafenib in nude mice. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have undergone a comprehensive study for their involvements in tumor treatments. The purpose of our study was to explore the biological effects and regulatory mechanisms of lncRNA LINC01194 (LINC01194) in laryngeal squamous cell carcinoma (LSCC). The levels of LINC01194 in 105 LSCC patients were detected by RT-qPCR. The diagnostic and prognostic value of LINC01194 in LSCC patients were statistically analyzed. The potential functions of LINC01194 in proliferation, apoptosis, and metastasis of LSCC cells were evaluated. The interaction among LINC01194, miR-655 and SOX18 was explored by bioinformatics analysis, luciferase reporter assays and biotinylated RNA pull-down. We found that the expression levels of LINC01194 were highly expressed in LSCC, which was negatively correlated with the clinical outcome of LSCC patients. The area under the ROC curve for LINC01194 was up to 0.8388. Functional assays indicated that LINC01194 knockdown distinctly inhibited LSCC cells proliferation, induced apoptosis, and also attenuated LSCC cells migration and invasion in vitro. Furthermore, we elucidated that LINC01194 promoted SOX18 expression in LSCC cells via functioning as a molecular sponge for miR-655. Overall, based on our findings, LINC01194 served as a tumor promoter and potentially represents a novel prognostic indicator and therapeutic target in LSCC. • : LncRNA LINC01194 was a novel LSCC-related lncRNA. • : Overexpression of LINC01194 promoted the proliferation and metastasis of LSCC cells. • : LncRNA LINC01194 sponged miR-655 to increase SOX18 expression. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancers, is an incurable and lethal disease. Although great progresses have been made in understanding the mechanism of ccRCC, metabolic reprogramming in ccRCC remains largely unclear. Here, we showed that lipid desatutation might be a metabolic hallmark of ccRCC. We demonstrated sterol regulatory element-binding protein 1 (SREBP1) is overexpressed in ccRCC cell lines and positively correlated with NF-κB activation. Further, SREBP1 is required for lipid desaturation and cell growth in ccRCC. Mechanistically, we demonstrated that SREBP1-driven lipid desaturation promotes NF-κB activation. Our finding reveals a crucial roles for SREBP1 in lipid desaturation of ccRCC through regulation of NF-κB signaling, which provides not only new insights in regulatory mode of NF-κB signaling but also a novel target for potential metabolic therapies. [ABSTRACT FROM AUTHOR]

Different regions and states of the human colon are likely to have a distinct influence on immune cell functions. Here we studied the immunometabolic mechanisms for spatial immune specialization and dysregulated immune response during ulcerative colitis at single-cell resolution. We revealed that the macrophages and CD8+ T cells in the lamina propria of the human colon possessed an effector phenotype and were more activated, while their lipid metabolism was suppressed compared with those in the epithelial. Also, IgA+ plasma cells accumulated in lamina propria of the sigmoid colon were identified to be more metabolically activated versus those in the cecum and transverse colon, and the improved metabolic activity was correlated with the expression of CD27. In addition to the immunometabolic reprogramming caused by spatial localization colon, we found dysregulated cellular metabolism was related to the impaired immune functions of macrophages and dendritic cells in patients with ulcerative colitis. The cluster of OSM+ inflammatory monocytes was also identified to play its role in resistance to anti -TNF treatment, and we explored targeted metabolic reactions that could reprogram them to a normal state. Altogether, this study revealed a landscape of metabolic reprogramming of human colonic immune cells in different locations and disease states, and offered new insights into treating ulcerative colitis by immunometabolic modulation. • We depicted a metabolic landscape of human colonic immune cells in different locations and states at single-cell resolution. • Immune cells in lamina propria possessed an effector phenotype but suppressed lipid metabolism versus those in epithelial. • Dysregulated cellular metabolism was related to the impaired immune functions in patients with ulcerative colitis. • We explored pathways related to anti-TNF resistance showing the potential immunometabolic modulation to ulcerative colitis. [ABSTRACT FROM AUTHOR]

Ferroptosis is a kind of cell death closely related to selective autophagy, such as ferritinophagy, lipophagy, clockophagy and chaperone-mediated autophagy. However, the role of reticulophagy, which specifically degrades endoplasmic reticulum (ER) fragments (also known as ER-phagy), in ferroptosis regulation is still unclear. In this study, we found that sorafenib (ferroptosis inducer) can effectively activate the receptor protein FAM134B-mediated ER-phagy, and FAM134B knockdown not only blocked ER-phagy but also significantly strengthened cellular sensitivity to ferroptosis without affecting macroautophagy. In vivo experiments also yielded similar results. These evidences provided new clues for ferroptosis regulation. Subsequently, bioinformatic analysis combined with RNA binding protein immunoprecipitation and polyribosome fractionation preliminarily indicated that PABPC1 can interact with FAM134B mRNA and promote its translation. Taken together, this study revealed the role of the PABPC1-FAM134B-ER-phagy pathway on ferroptosis, providing important evidence for novel anti-cancer strategies. • ER-phagy was effectively induced by sorafenib in HCC cells. • FAM134B-mediated ER-phagy was closely related to ferroptosis. • FAM134B knockdown-mediated ER-phagy inhibition might enhance cellular sensitivity to ferroptosis. [ABSTRACT FROM AUTHOR]

In this study, gallium- and gelatin-modified strontium-doped hydroxyapatite (SrHA-Gel-Ga) bilayer coatings were prepared on titanium substrates by electrodeposition and spin-coating techniques. The results showed that gallium and gelatin were uniformly doped into the SrHA coatings, which exhibited good hydrophilicity and bioactivity. Furthermore, SrHA-Gel-Ga demonstrated good antimicrobial properties against E. coli and S. aureus, especially S. aureus. The co-doping of Sr and gelatin in the coatings was effective in mitigating the cytotoxicity of Ga. SrHA-Gel-Ga was better able to promote the adhesion, proliferation and early differentiation of MC3T3-E1 cells. This study provides a new strategy for the development of anti-infective bone repair coatings. • A novel SrHA-Gel-Ga coating was constructed for infected bone defects. • The coating exhibited good hydrophilicity and bioactivity. • The coating had a good antimicrobial effect for E. coli and S. aureus. • The SrHA-Gel-Ga coating possessed excellent cytocompatibility. [ABSTRACT FROM AUTHOR]

Human articular cartilage is subjected to repetitive mechanical loading during life time. As the only cellular component of articular cartilage, chondrocytes play a key role in the mechanotransduction within this tissue. The mechanoresponses of chondrocytes are largely determined by the cytoskeleton. Vimentin intermediate filaments, one of the major cytoskeletal components, have been shown to regulate chondrocyte phenotype. However, the contribution of vimentin in chondrocyte mechanoresponses remains less studied. In this study, we seeded goat articular chondrocytes on a soft polyacrylamide gel, and disrupted the vimentin cytoskeleton using acrylamide. Then we applied a transient stretch or compression to the cells, and measured the changes of cellular stiffness and traction forces using Optical Magnetic Twisting Cytometry and Traction Force Microscopy, respectively. In addition, to study the effects of vimentin disruption on the intracellular force generation, we treated the cells with a variety of reagents that are known to increase or decrease cytoskeletal tension. We found that, after a compression, the contractile moment and cellular stiffness were not affected in untreated chondrocytes, but were decreased in vimentin-disrupted chondrocytes; after a stretch, vimentin-disrupted chondrocytes showed a lower level of fluidization-resolidification response compared to untreated cells. Moreover, vimentin-disrupted chondrocytes didn't show much difference to control cells in responding to reagents that target actin and ROCK pathway, but showed a weaker response to histamine and isoproterenol. These findings confirmed chondrocyte vimentin as a major contributor in withstanding compressive loading, and its minor role in regulating cytoskeletal tension. [ABSTRACT FROM AUTHOR]