Chemoselective α-Sulfidation of Amides Using Sulfoxide Reagents

10.26434/chemrxiv.12755879 ◽

2020 ◽

Author(s):

Mario Leypold ◽

Kyan A. D’Angelo ◽

Mohammad Movassaghi

Keyword(s):

Critical Role ◽

Single Step ◽

Mechanistic Studies ◽

Selective Functionalization ◽

Sulfonium Ions ◽

Activation Conditions ◽

Tertiary Amides ◽

Amide Activation

The direct α-sulfidation of tertiary amides using sulfoxide reagents under electrophilic amide activation conditions is described. Employing readily available reagents, selective functionalization takes place to generate isolable sulfonium ions en route to α-sulfide amides. Mechanistic studies support the critical role of activated sulfoxides that promote the desired transformation. For benzylic amide substrates, a single-step protocol featuring a spontaneous dealkylation step of a sulfonium ion intermediate was developed.

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Mechanistic Studies of Single-Step Styrene Production Catalyzed by Rh Complexes with Diimine Ligands: An Evaluation of the Role of Ligands and Induction Period

ACS Catalysis ◽

10.1021/acscatal.9b01480 ◽

2019 ◽

Vol 9 (8) ◽

pp. 7457-7475 ◽

Cited By ~ 9

Author(s):

Weihao Zhu ◽

Zhongwen Luo ◽

Junqi Chen ◽

Chang Liu ◽

Lu Yang ◽

...

Keyword(s):

Induction Period ◽

Single Step ◽

Mechanistic Studies ◽

Diimine Ligands ◽

Styrene Production

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The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes

Frontiers in Physiology ◽

10.3389/fphys.2021.715852 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yanping Zheng ◽

Ying Ran ◽

Hongxia Zhang ◽

Bangmao Wang ◽

Lu Zhou

Keyword(s):

Gut Microbiome ◽

Metabolic Pathways ◽

Liver Diseases ◽

Critical Role ◽

Short Chain Fatty Acids ◽

Primary Biliary Cholangitis ◽

Mechanistic Studies ◽

Autoimmune Liver Diseases ◽

Acid Metabolites

Recent studies have identified the critical role of microbiota in the pathophysiology of autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Metagenomic studies reveal significant decrease of gut bacterial diversity in AILDs. Although profiles of metagenomic vary widely, Veillonella is commonly enriched in AIH, PBC, and PSC. Apart from gut microbiome, the oral and bile microbiome seem to be associated with these diseases as well. The functional analysis of metagenomics suggests that metabolic pathways changed in the gut microbiome of the patients. Microbial metabolites, including short-chain fatty acids (SCFAs) and microbial bile acid metabolites, have been shown to modulate innate immunity, adaptive immunity, and inflammation. Taken together, the evidence of host–microbiome interactions and in-depth mechanistic studies needs further accumulation, which will offer more possibilities to clarify the mechanisms of AILDs and provide potential molecular targets for the prevention and treatment in the future.

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Chitinase 3-like-1 Contributes to Acetaminophen-induced Liver Injury by Promoting Hepatic Platelet Recruitment

10.1101/2021.04.08.439034 ◽

2021 ◽

Author(s):

Zhao Shan ◽

Leike Li ◽

Constance Lynn Atkins ◽

Meng Wang ◽

Yankai Wen ◽

...

Keyword(s):

Liver Injury ◽

Tissue Injury ◽

Critical Role ◽

Molecular Pathways ◽

Mechanistic Studies ◽

Wild Type ◽

Critical Pathway ◽

Podoplanin Expression ◽

Platelet Accumulation

Hepatic platelet accumulation contributes to acetaminophen (APAP)-induced liver injury (AILI). However, little is known about the molecular pathways involved in platelet recruitment to the liver and whether targeting such pathways could attenuate AILI. The present study unveiled a critical role of chitinase 3-like-1 (Chi3l1) in hepatic platelet recruitment during AILI. Increased Chi3l1 and platelets in the liver were observed in patients and mice overdosed with APAP. Compared to wild-type (WT) mice, Chi3l1-/- mice developed attenuated AILI with markedly reduced hepatic platelet accumulation. Mechanistic studies revealed that Chi3l1 signaled through CD44 on macrophages to induce podoplanin expression, which mediated platelet recruitment through C-type lectin-like receptor 2. Moreover, APAP treatment of CD44-/- mice resulted in much lower numbers of hepatic platelets and liver injury than WT mice, a phenotype similar to that in Chi3l1-/- mice. Recombinant Chi3l1 could restore hepatic platelet accumulation and AILI in Chi3l1-/- mice, but not in CD44-/- mice. Importantly, we generated anti-Chi3l1 monoclonal antibodies and demonstrated that they could effectively inhibit hepatic platelet accumulation and AILI. Overall, we uncovered the Chi3l1/CD44 axis as a critical pathway mediating APAP-induced hepatic platelet recruitment and tissue injury. We demonstrated the feasibility and potential of targeting Chi3l1 to treat AILI.

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The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

Perspectives on Language Learning and Education ◽

10.1044/lle15.2.50 ◽

2008 ◽

Vol 15 (2) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Amy Philofsky

Keyword(s):

Language Development ◽

Critical Role ◽

Children With Autism ◽

Autism Spectrum ◽

Children With Asd ◽

Prevalence Estimates ◽

Notable Increase ◽

Screening Assessment ◽

Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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