Designing Low Toxic Deep Eutectic Solvents for the Green Recycle of Lithium-Ion Batteries Cathodes.

The Lithium-ion battery (LIB) is one of the main energy storage equipment. Its cathode material contains Li, Co, and other valuable metals. Therefore, recycling spent LIBs can reduce environmental pollution and resource waste, which is significant for sustainable development. However, traditional metallurgical methods are not environmentally friendly, with high cost and environmental toxicity. Recently, the concept of green chemistry gives rise to environmental and efficient recycling technology, which promotes the transition of recycling solvents from organic solvents to green solvents represented by deep eutectic solvents (DESs). DESs are considered as ideal alternative solvents in extraction processes, attracting great attention due to their low cost, low toxicity, good biodegradability, and high extraction capacity. It is very important to develop the DESs system for LIBs recycling for sustainable development of energy and green economic development of recycling technology. In this work, the applications and research progress of DESs in LIBs recovery are reviewed, and the physicochemical properties such as viscosity, toxicity and regulatory properties are summarized and discussed. In particular, the toxicity data of DESs are collected and analyzed. Finally, the guidance and prospects for future research are put forward, aiming to explore more suitable DESs for recycling valuable metals in batteries.

Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.

Deubiquitinases (DUBs) remove ubiquitin from substrates and play crucial roles in diverse biological processes. However, our understanding of deubiquitination in viral replication remains limited. Employing an oncogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) to probe the role of protein deubiquitination, we found that Ovarian tumor family deubiquitinase 4 (OTUD4) promotes KSHV reactivation. OTUD4 interacts with the replication and transcription activator (K-RTA), a key transcription factor that controls KSHV reactivation, and enhances K-RTA stability by promoting its deubiquitination. Notably, the DUB activity of OTUD4 is not required for K-RTA stabilization; instead, OTUD4 functions as an adaptor protein to recruit another DUB, USP7, to deubiquitinate K-RTA and facilitate KSHV lytic reactivation. Our study has revealed a novel mechanism whereby KSHV hijacks OTUD4-USP7 deubiquitinases to promote lytic reactivation, which could be potentially harnessed for the development of new antiviral therapies.

The deubiquitinase OTUD4 inhibits the expression of antimicrobial peptides in Paneth cells to support intestinal inflammation and bacterial infection.

Dysfunction of the intestinal epithelial barrier causes microbial invasion that would lead to inflammation in the gut. Antimicrobial peptides (AMPs) are essential components of the intestinal epithelial barrier, while the regulatory mechanisms of AMPs expression are not fully characterized. Here, we report that the ovarian tumor family deubiquitinase 4 (OTUD4) in Paneth cells restricts the expression of AMPs and thereby promotes experimental colitis and bacterial infection. OTUD4 is upregulated in the inflamed mucosa of ulcerative colitis patients and in the colon of mice treated with dextran sulfate sodium salt (DSS). Knockout of OTUD4 promotes the expression of AMPs in intestinal organoids after stimulation with lipopolysaccharide (LPS) or peptidoglycan (PGN) and in the intestinal epithelial cells (IECs) of mice after DSS treatment or Salmonella typhimurium (S.t.) infection. Consistently, Vil-Cre;Otud4fl/fl mice and Def-Cre;Otud4fl/fl mice exhibit hyper-resistance to DSS-induced colitis and S.t. infection compared to Otud4fl/fl mice. Mechanistically, knockout of OTUD4 results in hyper K63-linked ubiquitination of MyD88 and increases the activation of NF-κB and MAPKs to promote the expression of AMPs. These findings collectively highlight an indispensable role of OTUD4 in Paneth cells to modulate AMPs production and indicate OTUD4 as a potential target for gastrointestinal inflammation and bacterial infection.

Safety and efficacy of acupuncture for anxiety and depression in patients with heart failure: A protocol for systematic review and meta-analysis.

BACKGROUND: In recent years, with the increase of patients with coronary heart disease, the number of patients with heart failure (HF) has also gradually increased. Coronary heart disease is one of the most common causes of HF. Anxiety and depression are frequent psychological disorders in patients with HF. Studies have shown that anxiety and depression can affect the quality of life of patients with HF, and can increase hospitalization and mortality. Conventional pharmacotherapy and psychotherapy have certain limitations. Acupuncture has therapeutic effects on heart disease, anxiety and depression, and has been widely used to relieve symptoms in patients with HF. This protocol aims to evaluate the safety and efficacy of acupuncture for anxiety and depression in patients with HF. METHODS: We will search the following databases: PubMed, Web of Science, Springer Cochrane Library, EMBASE, MEDLINE, WHO international clinical trials registry platform, China National Knowledge Infrastructure database, Wan Fang database, Chinese scientific journal database and Chinese Biomedical Literature Database. The databases will be searched from initiate to October 1, 2022. Two reviewers will screen and document eligible studies based on inclusion and exclusion criteria. Two reviewers will independently perform data analysis and bias risk assessment. Review Manager version 5.4 software will be used for meta-analysis. RESULTS: This study will explore the efficacy and safety of acupuncture for anxiety and depression in patients with HF. CONCLUSION: The results of this study will provide high-quality evidence for evaluating the safety and efficacy of acupuncture for anxiety and depression in patients with HF.

Huotan Jiedu Tongluo Decoction Inhibits Balloon-Injury-Induced Carotid Artery Intimal Hyperplasia in the Rat through the PERK-eIF2α-ATF4 Pathway and Autophagy Mediation.

In-stent restenosis (ISR) is the main factor affecting the outcome of percutaneous coronary intervention (PCI), and its main pathological feature is neointimal hyperplasia. Huotan Jiedu Tongluo decoction (HTJDTLD) is an effective traditional Chinese medicine (TCM) prescription for the treatment of vascular stenosis diseases. However, the precise anti-ISR mechanism of HTJDTLD remains unclear. Here, we investigated whether HTJDTLD can inhibit the excessive activation of endoplasmic reticulum stress (ERS) and reduce the level of autophagy factors through regulating the PERK-eIF2α-ATF4 pathway, thereby inhibiting the proliferation of the intima of blood vessels damaged by balloon injury (BI) and preventing the occurrence of ISR. In this study, a 2F Fogarty balloon was used to establish a common carotid artery (CCA) BI model in male Sprague-Dawley rats. Then, HTJDTLD (16.33 g/kg/d) or atorvastatin (1.19 mg/kg/d) was administered by gavage. Four weeks later, hematoxylin-eosin (HE) and Masson staining of the injured CCA were performed to observe the histological changes in the CCA. Immunohistochemistry (IHC) was used to assess the proliferation and dedifferentiation of vascular smooth muscle cells (VSMCs) in the CCA. Western blotting and RT-PCR were used to measure the expression of ERS- and autophagy-related proteins and mRNAs in the CCA. The results indicated that HTJDTLD significantly alleviated BI-induced carotid artery intimal hyperplasia and fibrosis and reduced the neointimal area (NIA) and NIA/medial area (MA) ratio. In addition, HTJDTLD inhibited the proliferation and dedifferentiation of VSMCs, reduced the expression of proliferating cell nuclear antigen (PCNA), and increased the smooth-muscle-α-actin- (SMα-actin-) positive area. HTJDTLD also significantly reduced the expression of the ERS-related factors: GRP78, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, and CHOP. In addition, the expression of the autophagy-related factors, Beclin1, LC3B, and ATG12, was significantly decreased. In addition, in vitro experiments showed that HTJDTLD inhibited the above-mentioned ERS signal molecules in human umbilical vein endothelial cells (HUVEC) and rat aortic smooth muscle cells (A7R5) induced by tunicamycin (TM) and played a crucial role in protecting cells from damage. HTJDTLD may be a very promising drug for the treatment of ISR.

Circ_0084582 Facilitates Cell Growth, Migration, Invasion, and Angiopoiesis in Osteosarcoma via Mediating the miR-485-3p/JAG1 Axis.

Osteosarcoma (OS) is the most representative bone cancer, and circular RNAs serve as pivotal regulators in the progression of OS. This research was designed to explore the role and functional mechanism of circ_0084582 in OS. Circ_0084582, microRNA-485-3p (miR-485-3p), and Jagged1 (JAG1) levels were measured by quantitative real-time polymerase chain reaction. Cell proliferation was examined via 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle progression was analyzed by flow cytometry. Wound healing and transwell assays were performed for evaluating cell migration and invasion. Angiopoiesis was assessed using the tube formation assay. Protein detection was conducted using Western blot. The target relation was identified by the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay. A xenograft experiment was applied for analyzing the effect of circ_0084582 on OS in vivo. Circ_0084582 was highly expressed in OS tissues and cells. Circ_0084582 knockdown reduced cell proliferation, cell cycle progression, migration, invasion, and angiopoiesis of OS cells. JAG1 was upregulated in OS, and its overexpression reversed the effects of circ_0084582 knockdown on OS cells. Circ_0084582 targeted miR-485-3p, and miR-485-3p targeted JAG1, and circ_0084582 could affect the JAG1 level by sponging miR-485-3p. The function of circ_0084582 in OS progression was also achieved by sponging miR-485-3p. Circ_0084582 knockdown decreased OS growth in vivo partly by the miR-485-3p-mediated JAG1 downregulation. These results indicate that circ_0084582 functions as a tumorigenic factor in OS via the regulation of miR-485-3p/JAG1 axis.

Profiles of COVID-19 clinical trials in the Chinese Clinical Trial Registry.

The COVID-19 pandemic has caused a global public health crisis. There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the COVID-19 pandemic. The Chinese scientists supported by private and government resources have adopted extensive efforts to identify effective drugs against the virus. To date, a large number of clinical trials addressing various aspects of COVID19 have been registered in the Chinese Clinical Trial Registry (ChiCTR), including more than 200 interventional studies. Under such an urgent circumstance, the scope and quality of these clinical studies vary significantly. Hence, this review aims to make a comprehensive analysis on the profiles of COVID-19 clinical trials registered in the ChiCTR, including a wide range of characteristics. Our findings will provide a useful summary on these clinical studies since most of these studies will encounter major challenges from the design to completion. It will be a long road for the outcomes of these studies to be published and international collaboration will help the ultimate goals of developing new vaccines and anti-viral drugs.

Induction of OTUD4 by viral infection promotes antiviral responses through deubiquitinating and stabilizing MAVS.

The activity and stability of the adapter protein MAVS (also known as VISA, Cardif and IPS-1), which critically mediates cellular antiviral responses, are extensively regulated by ubiquitination. However, the process whereby MAVS is deubiquitinated is unclear. Here, we report that the ovarian tumor family deubiquitinase 4 (OTUD4) targets MAVS for deubiquitination. Viral infection leads to the IRF3/7-dependent upregulation of OTUD4 which interacts with MAVS to remove K48-linked polyubiquitin chains, thereby maintaining MAVS stability and promoting innate antiviral signaling. Knockout or knockdown of OTUD4 impairs RNA virus-triggered activation of IRF3 and NF-κB, expression of their downstream target genes, and potentiates VSV replication in vitro and in vivo. Consistently, Cre-ER Otud4fl/fl or Lyz2-Cre Otud4fl/fl mice produce decreased levels of type I interferons and proinflammatory cytokines and exhibit increased sensitivity to VSV infection compared to their control littermates. In addition, reconstitution of MAVS into OTUD4-deficient cells restores virus-induced expression of downstream genes and cellular antiviral responses. Together, our findings uncover an essential role of OTUD4 in virus-triggered signaling and contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.