Water-Compatible Iminium Activation: Highly Enantioselective Organocatalytic Michael Addition of Malonates to α,β-Unsaturated Enones

The highly enantioselective Michael addition of malonates to α,β-unsaturated ketones in water was reported to be catalyzed by a primary−secondary diamine catalyst containing a long alkyl chain. This asymmetric Michael addition process was found to be effective for a variety of α,β-unsaturated ketones

Gold-Catalyzed Intermolecular Nitrene Transfer from 2<i>H</i>‑Azirines to Ynamides: A Direct Approach to Polysubstituted Pyrroles

An effective gold-catalyzed intermolecular nitrene transfer by the reaction of 2<i>H</i>-azirines and ynamides is reported, which provides highly substituted pyrroles in a straightforward manner. This transformation proceeds under mild conditions and gives the polysubstituted pyrroles in good-to-excellent yields. Preliminary results indicate that a nongold carbenoid pathway is preferred for current pyrrole synthesis

Copper(II)-Mediated Dehydrogenative Cross-Coupling of Heteroarenes

Cu(OAc)₂-mediated dehydrogenative cross-coupling between two heteroarenes has been realized in the absence of any other additive. A mechanism involving a formal Cu(II) to Cu(0) route by convergent disproportionation of the copper mediator is proposed and has been evidenced by copper mirror formation during the reaction. This synthetic protocol provides a concise and “green” access to unsymmetrical biheteroarenes bearing structural motifs of substantial utility in organic synthesis

Table_1_The Antibody Assay in Suspected Autoimmune Encephalitis From Positive Rate to Test Strategies.docx

ObjectiveThe aim of this study was to analyze the positive rate and test strategies of suspected autoimmune encephalitis (SAE) based on an antibody assay.MethodsPatients who were diagnosed with suspected autoimmune encephalitis in Guizhou Province between June 1, 2020, and June 30, 2021 and who had anti-neuronal autoantibodies detected by Guizhou KingMed Diagnostics Group Co., Ltd. were included in this study. The positive rate and the test strategies were analyzed based on the results of the anti-neuronal antibody assay.ResultsA total of 263 patients with SAE were included, 58.2% (153/263) of whom were males, with a median age of 33 years (1-84 years). 84% (221/263) of all patients completed both serum and CSF tests. A total of 46.0% (121/263) of SAE patients received the AE-6 examination package. The antibody-positive rate was 9.9% (26/263) in the current cohort, with an observed incidence of antibody positive of 0.2 in 100,000 (26/11,570,000, 95% CI: 0.15-0.30), and the estimated incidence was 0.9 in 100,000 (95% CI: 0.84-0.95) of the total population. A total of 9 different anti-neuronal antibodies were detected. Anti-NMDAR antibody was the most common antibody in 46.2% (12/26) of subjects, 70.0% (7/10) of whom were children, followed by anti-Caspr2 antibody in 30.8% (8/26); the remaining 7 antibodies were detected in 23.1% (6/26) of the population. There were no obvious differences among age, sex or season in the positive rate of anti-neuronal antibodies. The cost of antibody testing per capita was $439.30 (SD±$195.10). The total cost of AE-14 was the highest at $48.016.81 (41.56%) among all examination packages.ConclusionsThis study described the positive rate associated with AE-related anti-neuronal antibodies and test strategies in the current cohort, which provides a basis for clinicians in clinical practice.</p

Table_1_The Identification of Differentially Expressed Genes Showing Aberrant Methylation Patterns in Pheochromocytoma by Integrated Bioinformatics Analysis.xlsx

Malignant pheochromocytoma (PHEO) can only be fully diagnosed when metastatic foci develop. However, at this point in time, patients gain little benefit from traditional therapeutic methods. Methylation plays an important role in the pathogenesis of PHEO. The aim of this research was to use integrated bioinformatics analysis to identify differentially expressed genes (DEGs) showing aberrant methylation patterns in PHEO and therefore provide further understanding of the molecular mechanisms underlying this condition. Aberrantly methylated DEGs were first identified by using R software (version 3.6) to combine gene expression microarray data (GSE19422) with gene methylation microarray data (GSE43293). An online bioinformatics database (DAVID) was then used to identify all overlapping DEGs showing aberrant methylation; these were annotated and then functional enrichment was ascertained by gene ontology (GO) analysis. The online STRING tool was then used to analyze interactions between all overlapping DEGs showing aberrant methylation; these results were then visualized by Cytoscape (version 3.61). Next, using the cytoHubba plugin within Cytoscape, we identified the top 10 hub genes and found that these were predominantly enriched in pathways related to cancer. Reference to The Cancer Genome Atlas (TCGA) further confirmed our results and further identified an upregulated hypomethylated gene (SCN2A) and a downregulated hypermethylated gene (KCNQ1). Logistic regression analysis and receiver operating characteristic (ROC) curve analysis indicated that KCNQ1 and SCN2A represent promising differential diagnostic biomarkers between benign and malignant PHEO. Finally, clinical data showed that there were significant differences in the concentrations of potassium and sodium when compared between pre-surgery and post-surgery day 1. These suggest that KCNQ1 and SCN2A, genes that encode potassium and sodium channels, respectively, may serve as putative diagnostic targets for the diagnosis and prognosis of PHEO and therefore facilitate the clinical management of PHEO.</p

Identification of an Iridium(III)-Based Inhibitor of Tumor Necrosis Factor‑α

The novel iridium­(III) complex <b>1</b> was verified as a potent inhibitor of the TNF-α–TNFR protein–protein interaction in vitro and in cellulo. The iridium­(III) center plays a critical role in organizing the structure of the bioactive metal complex, as the isolated ligands were found to be completely inactive. Both iridium enantiomers inhibited TNF-α-induced NF-κB activity and TNF-α–TNFR binding. <b>1</b> represents a promising scaffold for the further development of more potent organometallic TNF-α inhibitors

sj-docx-2-tan-10.1177_17562864211057661 – Supplemental material for Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Supplemental material, sj-docx-2-tan-10.1177_17562864211057661 for Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients by Kimberley Allen-Philbey, Stefania De Trane, Zhifeng Mao, Cesar Álvarez-González, Joela Mathews, Amy MacDougall, Andrea Stennett, Xia Zhou, Ozlem Yildiz, Ashok Adams, Lucia Bianchi, Camilla Blain, Christine Chapman, Karen Chung, Cris S Constantinescu, Catherine Dalton, Rachel A Farrell, Leonora Fisniku, Helen Ford, Bruno Gran, Jeremy Hobart, Zhaleh Khaleeli, Miriam Mattoscio, Sue Pavitt, Owen Pearson, Luca Peruzzotti-Jametti, Antonio Scalfari, Basil Sharrack, Eli Silber, Emma C Tallantyre, Stewart Webb, Benjamin P Turner, Monica Marta, Sharmilee Gnanapavan, Gunnar Juliusson, Gavin Giovannoni, David Baker and Klaus Schmierer in Therapeutic Advances in Neurological Disorders</p

sj-docx-1-tan-10.1177_17562864211057661 – Supplemental material for Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Supplemental material, sj-docx-1-tan-10.1177_17562864211057661 for Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients by Kimberley Allen-Philbey, Stefania De Trane, Zhifeng Mao, Cesar Álvarez-González, Joela Mathews, Amy MacDougall, Andrea Stennett, Xia Zhou, Ozlem Yildiz, Ashok Adams, Lucia Bianchi, Camilla Blain, Christine Chapman, Karen Chung, Cris S Constantinescu, Catherine Dalton, Rachel A Farrell, Leonora Fisniku, Helen Ford, Bruno Gran, Jeremy Hobart, Zhaleh Khaleeli, Miriam Mattoscio, Sue Pavitt, Owen Pearson, Luca Peruzzotti-Jametti, Antonio Scalfari, Basil Sharrack, Eli Silber, Emma C Tallantyre, Stewart Webb, Benjamin P Turner, Monica Marta, Sharmilee Gnanapavan, Gunnar Juliusson, Gavin Giovannoni, David Baker and Klaus Schmierer in Therapeutic Advances in Neurological Disorders</p