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Liver fibrosis is a very common health problem and currently lacks effective treatments. Cullin RING E3 ligases (CRLs) regulate the turnover of ~20% of mammalian cell proteins. Neddylation, the process by which NEDD8 is covalently attached to cullin proteins through sequential enzymatic reactions, is critical for the activation of CRLs and was recently found to be elevated in liver fibrosis. NEDD8-activating enzyme El-specific inhibition led to the reduced liver damage characterized by decreased apoptosis, inflammation, and fibrosis. However, the relevance of a co-E3 ligase, DCN1, in liver fibrosis remains unclear. Here, a novel and potent DCN1-UBC12 interaction inhibitor HZX-960 was discovered with an [IC.sub.50] value of 9.37 nmol/L, which could inhibit the neddylation of cullin3. Importantly, we identified that HZX-960 treatment could attenuate transforming growth factor [beta]-induced liver fibrotic responses by reducing the deposition of collagen I and [alpha]-smooth muscle actin, and upregulating cellular NF-E2-related factor 2, hemeoxygenase 1, and NADPH quinone oxidoreductase-1 levels in two hepatic stellate cell lines. Additionally, DCN1 was shown to be unregulated in CCI4-induced mice liver tissue, and liver fibrotic signaling in mice was reduced by HZX-960. Therefore, our data demonstrated that HZX-960 possessed anti-liver fibrosis ability and that DCN1 may be a potential therapeutic target for liver fibrosis treatment. Keywords: DCN1, UBC12, interaction, NRF2, liver fibrosis La fibrose du foie constitue un probleme de sante tres repandu et il n'existe actuellement aucun traitement efficace. Les ligases E3 CRL (Cullin Ring E3 Ligases) regulent le renouvellement de ~20 % des proteines des cellules de mammiferes. La neddylation, le processus par lequel NEDD8 est attache de maniere covalente aux proteines cullines par des reactions enzymatiques sequentielles, est essentielle pour l'activation des CRL et il a ete recemment decouvert qu'elle etait elevee dans la fibrose du foie. L'inhibition specifique de l'enzyme activatrice de NEDD8 El, a conduit a la reduction des lesions hepatiques caracterisees par une diminution de l'apoptose, de l'inflammation et de la fibrose. Cependant, l'importance d'une ligase co-E3, DCN1, dans la fibrose hepatique reste floue. Les auteurs ont decouvert ici un nouvel inhibiteur puissant de l'interaction DCN1-UBC12, le HZX-960, dont la valeur de [CI.sub.50] est de 9,37 nmol/L et qui peut inhiber la neddylation de la culline3. Mais surtout, ils ont identifie que le traitement par le HZX-960 pouvait attenuer les reponses fibrotiques hepatiques induites par le TGF[beta] en reduisant le depot de collagene I et [alpha]-SMA, et en regulant a la hausse les niveaux cellulaires de NRF2, HO-1 et NQO1 dans deux lignees de cellules de Kupfer. De plus, il a ete demontre que DCN1 n'etait pas regule dans le tissu hepatique de souris expose au CCI4, et que la signalisation de la fibrose hepatique chez les souris etait reduite par le HZX-960. Par consequent, ces donnees ont demontre que le HZX-960 possede une capacite anti-fibrose hepatique, et que DCN1 peut etre une cible therapeutique potentielle pour le traitement de la fibrose hepatique. [Traduit par la Redaction] Mots-cles : DCN1, UBC12, interaction, NRF2, fibrose du foie, Introduction Liver fibrosis, as a regenerative process, was observed in various chronic liver injuries, including nonalcoholic fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and hepatitis B and C, which [...]

The last 50 years have witnessed ecolinguistics come into bloom as a mature domain. This paper aims to examine the half-century development of ecolinguistics by reviewing its backgrounds, definitions, strands, and approaches, and also briefly previewing its future horizons. The birth of ecolinguistics can be attributed to such ecological necessities as the ecological crisis as an essential root, and an ecological perspective for linguistics as a linguistic necessity, together with six ecolinguistic turns in this domain (Section 2). Since the emergence of ecolinguistics in the 1970s, various definitions for ecolinguistics as an evolving concept have come into being, involving the geographical, conceptual, disciplinary, methodological, and practical sides (Section 3). Figures who have contributed to the development of this domain can be divided into old strands like Haugenian and Hallidayan ecolinguistics, as well as new strands such as strong ecolinguistics and the latest radical embodied ecolinguistics (Section 4). Given the diverse definitions and strands, a set of approaches have taken shape, ranging from the Haugenian approach to ecological discourse analysis (Section 5). Due to major problems found in reviewing four parts of ecolinguistics, it is high time three shifts in perspective be put into effect in ecolinguistics that can promise its future horizons.

MXene quantum dots (MQDs), an emerging zero‐dimensional nanomaterial, have garnered significant attention from researchers due to their distinctive physical and chemical properties. In this study, cysteine‐functionalized Ti3C2 MQDs were synthesized using a facile hydrothermal methods, resulting in the functionalized Ti3C2 MQDs exhibiting intense blue fluorescence attributed to size‐dependent effects and surface defects. Furthermore, the cysteine‐functionalized Ti3C2 MQDs exhibit excitation wavelength‐dependent emission behavior and serve as a highly sensitive fluorescent probe for Ag+ detection with an impressive low limit of detection (LOD) of 0.015 μM. Moreover, they demonstrate exceptional sensitivity and selectivity in determining Ag+. This study presents a novel approach for the detection of Ag+ and highlights the immense potential of cysteine‐functionalized Ti3C2 MQDs in environmental applications. [ABSTRACT FROM AUTHOR]

Objective Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer. Methods CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan–Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay. Results CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966–1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice. Conclusion Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Fine-tuned interaction between reacting molecules and metal surface is of great importance in heterogeneous catalysis for the design of highly selective processes. Conventional strategies based on adjusting the intrinsic catalyst properties such as particle size, metal-support interaction and morphology suffer from complicated and time-consuming synthetic procedures. Recently, the modification of metal nanoparticles with non-metallic promoters has been demonstrated as an effective tool to regulate the interfacial environment of metallic catalysis. Herein, we will give an overview of recent progress in this area. A general analysis will be proposed about the electronic, steric effects and new functionalities imposed by non-metallic promoters of metal catalysts. The potential for the selectivity enhancement of the promoted metal catalysts in various industrially important reactions is discussed. [ABSTRACT FROM AUTHOR]