Palladium-Catalyzed Cascade Carbonylative Synthesis of Perfluoroalkyl and Carbonyl-Containing 3,4-Dihydroquinolin-2(1H)-one Derivatives.

A palladium-catalyzed cascade radical cyclization and carbonylation of 1,7-enynes with perfluoroalkyl iodides and alcohols has been described. This procedure provides a facile and efficient approach for the construction of 3,4-dihydroquinolin-2(1H)-one skeletons by using benzene-1,3,5-triyl triformate (TFBen) as the CO source. This method enables the incorporation of both perfluoroalkyl and carbonyl units into the 3,4-dihydroquinolin-2(1H)-one skeletons, producing a variety of 3,4-dihydroquinolin-2(1H)-one derivatives in moderate to high yields and with excellent E/Z selectivity.

Additive-Controlled Divergent Synthesis of Indole and 4H-Benzo[d][1,3]oxazine Derivatives: Palladium-Catalyzed Carbonylative Cyclization of 2-Alkynylanilines and Benzyl Chlorides.

A palladium-catalyzed divergent carbonylative synthesis of indoles and 4H-benzo[d][1,3]oxazines from 2-alkynylanilines and benzyl chlorides with benzene-1,3,5-triyl triformate (TFBen) as the CO source has been developed. The reaction using AlCl3 as the additive produced various indoles in high yields, while a series of 4H-benzo[d][1,3]oxazines was achieved in moderate yields with AcOH as the additive.

Palladium-catalyzed carbonylative synthesis of aryl esters from p-benzoquinones and aryl triflates.

A palladium-catalyzed dicarbonylation of p-benzoquinones with aryl triflates has been developed. Using Cr(CO)6 as the CO source, the reaction proceeds smoothly and efficiently to give a series of aryl esters in moderate to good yields (up to 90%).

Supported Palladium-Catalyzed Carbonylative Synthesis of Diaryl Ketones from Aryl Bromides and Arylboronic Acids.

A palladium supported on graphitic carbon nitride (Pd/g-C3 N4 ) catalyzed carbonylative reaction of aryl bromides and arylboronic acids by has been developed for the construction of diaryl ketones. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction proceeded well to give various diaryl ketones in moderate to good yields.

Prevalence of depression during the SARS, MERS, and COVID-19 pandemics: A protocol for overview of systematic reviews.

BACKGROUND: The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has emerged to be the biggest global health threat worldwide. COVID-19 marks the emergence of the third large-scale epidemic related to the coronavirus, after SARS-CoV in 2002 and Middle-East respiratory syndrome coronavirus (MERSCoV) in 2012. The pandemic has had a harmful effect on the public mental health, especially on depression. Increasing systematic reviews (SRs) of coronavirus were focusing on depression. However, the methodological quality of these SRs is unclear. Therefore, to evaluate and compare the normativity of report of SR, we conducted a comprehensive overview of depression during the SARS, MERS, and COVID-19 pandemics. METHODS: Two independent reviewers will conduct comprehensively searches in PubMed, EMBASE.com, Web of Science, the Cochrane Library, Chinese biomedical literature database (CBM), Chinese National Knowledge Infrastructure (CNKI), Wan fang Database, Chongqing VIP (CQVIP). Reference lists of articles, gray literature, and conference proceedings will also be searched. We will extract the data and assess the methodological quality using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) measurement tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. General characteristics of the eligible SRs will be summarized and described. We will provide AMSTAR-2 and PRISMA assessments in tabular form for each review, the total percentage of each item will be calculated. Endnote X8 and EXCEL will be used. RESULTS: Using the draft search strategy of databases, 8 SRs met the a priori criteria and were included. The overview of SRs will be published in a peer-reviewed journal. CONCLUSION: Our overview will be a comprehensive synthesis of the existing systemic review on depression with SARS, MERS, and COVID-19. PROTOCOL REGISTRATION: INPLASY202080003.

Critical appraisal of clinical practice guidelines for depression in children and adolescents: A protocol for systematic review.

BACKGROUND: Depression as a clinically significant and growing public health issue is the third leading cause of disability. Adolescent-onset depression has been associated with psychiatric, anxiety disorders, suicidality, medical comorbidities, and an elevated risk of major depressive disorder episodes later in life. How to effectively identify, prevent, and treat depression has become one of the key points of discussion among medical institutions/departments. With the importance of depression being emphasized, countries/organizations around the world have developed guidelines for clinical practice related to depression for different groups of people to guide medical staff to implement scientific, effective, and standardized depression management. However, the quality of such guidelines is not yet clear, which is not conducive to the selection of medical staff and affects clinical application to a certain extent. This study aims to evaluate the rigor of the development of clinical practice guidelines (CPGs) for depression in children and adolescents and will identify, in these documents, the recommendations for depression in children and adolescents. METHODS: Electronic databases and specific databases of CPGs will be searched. Study selection and data extraction will be performed independently by 2 reviewers. The AGREE II Instrument and RIGHT checklist will be used to assess the methodological quality and reporting quality of included CPGs about depression in children and adolescents. We will also analyze consistency and inconsistency of the recommendations in CPGs, including assessment, diagnosis, screening, treatment, and management. Bubble charts will be used to show the differences in methodological and reporting quality. Subgroup analysis will be conducted according to the result of evaluation. Excel and Endnote X9 will be used. RESULTS: Using the search drafts of electronic databases, we included 6 CPGs. The results of our study will be published in a peer-reviewed journal. CONCLUSIONS: Our study will provide systematic evidence for existing CPGs for depression in children and adolescents and provide a guidance for CPGs users. PROTOCOL REGISTRATION: INPLASY202080002.

Chelating Group Enabled Palladium-Catalyzed Regiodivergent Carbonylative Synthesis of 2,3-Dihydroquinolin-4(1H)-ones.

A new procedure on palladium-catalyzed carbonylative cyclization of N-(2-pyridyl)sulfonyl (N-SO2 Py)-2-iodoanilines with terminal alkenes has been developed for the rapid construction of dihydroquinolin-4(1H)-one scaffolds. Enabled by the chelating group and using benzene-1,3,5-triyl triformate (TFBen) as the CO source, both aromatic and aliphatic alkenes were smoothly transformed into the corresponding 2,3-dihydroquinolin-4(1H)-ones in good yields with excellent regioselectivities. Notably, the reaction of aromatic alkenes produces 2-aryl-2,3-dihydroquinolin-4(1H)-ones, while 3-alkyl-2,3-dihydroquinolin-4(1H)-ones were obtained when aliphatic alkenes were used. This protocol has been applied in the synthesis of antitumor agent A as well.

Ex Situ Generation of Difluorodiazoethane (CF2HCHN2): Application in the Regioselective Synthesis of CF2H-Containing Pyrazoles.

A new method for the ex situ generation of difluorodiazoethane (CF2HCHN2) and a procedure for its efficient use in [3 + 2] cycloaddition with nitroolefins by the AcOH/O2 catalyst system were developed by using a simple two-chamber system. The method provides a facile and straightforward access to a series of 4-substituted 5-difluoromethyl-3-nitro-1H-pyrazoles that are of interest in medicinal chemistry. Interestingly, the key factor for the success of this method is the efficient preparation of CF2HCHN2 by an ex situ process.

Efficacy of melanoma patients treated with PD-1 inhibitors: Protocol for an overview, and a network meta-analysis of randomized controlled trials.

BACKGROUND: Melanoma is a malignant tumor of melanocytes that produces pigments and can occur in the whole body. It is characterized by strong invasiveness, high metastasis rate and poor prognosis, and brings heavy burden to patients and society. In order to find the most effective and safe treatment measures, in this study, a network meta-analysis (NMA) for randomized controlled trials (RCTs) of advanced melanoma treated with PD-1 inhibitors will be conducted based on the existing systematic reviews (SRs) of PD-1 inhibitor in the treatment of advanced melanoma. METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library were searched on December 18, 2018 to obtain systematic reviews of PD-1 inhibitor in the treatment of advanced melanoma. Assessing the Methodological Quality of Systematic Reviews (AMSTAR2) will be used to assess the methodological quality of systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be applied to evaluate the evidence quality of outcome measures, and the Cochrane's risk of bias tool will be utilized to appraise risks of bias of each embedded RCTs. And the outcomes are overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Hazard ratio (HR) or odds ratio (OR) with their 95% confidence interval (CI) were used to synthesize dichotomous outcomes, while the mean difference (MD) for the continuous variables. R3.5.1 will be used to create a network evidence map for direct and indirect comparative analysis. RESULTS: This study will provide a comprehensive summary of the current evidences related to the efficacy and safety of PD-1 inhibitor in advanced melanoma. CONCLUSION: Our findings will be useful to assist clinicians make reasonable decisions to the treatment of advanced melanoma. ETHICS AND COMMUNICATION: It is unnecessary for this NMA to acquire an ethical approval, because it is based on published researches. PROSPERO REGISTRATION NUMBER: CRD42019120017.

A Protocol for the Synthesis of CF2H-Containing Pyrazolo[1,5- c]quinazolines from 3-Ylideneoxindoles and in Situ Generated CF2HCHN2.

Herein is disclosed a selective and facile approach for the construction of CF2H-containing pyrazolo[1,5- c]quinazolines from easily accessible 3-ylideneoxindoles and in situ generated CF2HCHN2. The reaction involving a [3 + 2] cycloaddition/1,3-H shift/rearrangement/dehydrogenation cascade proceeded smoothly at room temperature in the absence of catalyst and additive. Moreover, this metal-free process along with mild conditions is desirable and valuable for the pharmaceutical industry. Importantly, this reaction features a broad substrate scope, good functional group tolerance, and gram-scale synthesis.

Diastereoselective [3 + 2] cycloaddition of 3-ylideneoxindoles with in situ generated CF2HCHN2: syntheses of CF2H-containing spirooxindoles.

An efficient [3 + 2] cycloaddition of 3-ylideneoxindoles with in situ generated CF2HCHN2 for the syntheses of spirooxindoles has been developed. This methodology gives access to a range of relatively complex spirooxindoles featuring a CF2H group and three contiguous stereogenic centers in up to 84% yield and 99 : 1 trans/cis.

Roles of A20 in autoimmune diseases.

A20 (TNFAIP3), known to inhibit NF-κB function by deubiquitinating-specific NF-κB signaling molecules, has been found in many cell types of the immune system. Recent findings suggest that A20 is essential for the development and functional performance of dendritic cell, B cell, T cell and macrophage. A number of studies further demonstrate that these cells are crucial in the pathogenesis of autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease, ankylosing arthritis, Sjögren's syndrome and rheumatoid arthritis. In this article, we focus on the recent advances on the roles of A20 in autoimmune diseases and discuss the therapeutic significance of these new findings.

The roles of Egr-2 in autoimmune diseases.

Being a member of the early growth response (Egr) family of transcription factors, Egr-2 is expressed in a variety of cell types of the immune system. Recent findings imply that Egr-2 is important in the development and function of T helper (Th) 17 cell, regulatory T (Treg) cell, as well as dendritic cell (DC). Although these cells perform significantly in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and systemic sclerosis, the roles of Egr-2 in the pathogenesis of autoimmune diseases can not be neglected. In this article, we will discuss recent findings about the important roles of Egr-2 in immune cells and the possible pathological roles of Egr-2 in autoimmune diseases.

Increased urinary 8-hydroxy-2'-deoxyguanosine levels in workers exposed to di-(2-ethylhexyl) phthalate in a waste plastic recycling site in China.

BACKGROUND: Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in industrial and diverse consumer products. Animal studies indicate DEHP caused developmental, reproductive, and hepatic toxicities. However, human studies of the potential effects of DEHP are limited. METHODS: The exposed site with a history of over 20 years of waste plastic recycling was located in Hunan Province, China. The reference site without known DEHP pollution source was about 50 km far away from the exposed site. In this study, 181 workers working in plastic waste recycling and 160 gender-age matched farmers were recruited. DEHP concentrations in water and cultivated soil samples, serum thyroid-stimulating hormone, malondialdehyde (MDA), superoxide dismutase (SOD), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and micronuclei frequency in human capillary blood lymphocytes were analyzed. RESULTS: Mean levels of DEHP were greater in environment at the recycling site than at reference site (industry wastewater for the exposed: 42.43 µg/l; well water: 14.20 vs. 0.79 µg/l, pond water: 135.68 vs. 0.37 µg/l, cultivated soil: 13.07 vs. 0.81 mg/kg, p < 0.05 for all). The workers had higher median levels of MDA (3.80 vs. 3.14 nmol/ml) and urinary 8-OHdG (340.37 vs. 268.18 µmol/mol creatinine) and decreased SOD activities (112.15 vs. 123.82 U/ml) than the reference group (p < 0.01 for all). Multivariate analysis revealed that the history of working in waste plastic recycling was an independent risk factor for the increased urinary 8-OHdG levels in the male workers (p < 0.01). CONCLUSIONS: The occupational DEHP exposure might contribute to oxidative deoxyribonucleic acid damage in the male workers.