Revised Mechanism of Gold-Catalyzed Thioallylation of Propiolates.

Gold-catalyzed enantioselective thioallylation of propiolates proved effective in delivering highly enantio-enriched α-allyl-β-thioacrylates. In this work, we report a revised mechanism for this process based on the new mechanistic experiments and kinetic data in the presence of a competitive inhibitor. The employment of thioethers as nucleophiles inevitably involves their competitive binding to the only catalytic site of the Au(I) catalyst, which may inhibit the activity.

Aged related human skin microbiome and mycobiome in Korean women.

We examined differences in the skin microbiome of two separate age groups to find key microbial and skin physiological indicators associated with aging. We recruited healthy Korean women 19-28 years old (Y-group) and 60-63 years old (O-group) and evaluated their cheek and forehead skin microbiome, including bacteria and fungi. The microbiome was significantly different by age group, with bacterial and fungal communities displaying higher alpha-diversity in the O-group than in the Y-group.

Long-Term Efficacy of Ultrasound-Guided Laser Ablation for Papillary Thyroid Microcarcinoma: Results of a 10-Year Retrospective Study.

The aim of this study was to evaluate the 10-year efficacy and safety of laser ablation (LA) for the treatment of solitary papillary thyroid microcarcinoma (PTMC). LA was performed on patients with low-risk PTMC (diagnosed using fine-needle aspiration cytology) who refused or were ineligible for surgery between 2008 and 2011. Ultrasonography was performed to evaluate the ablated volumes and potential recurrences on the day after the procedure, as well as at 1 week, 1, 3, and 6 months, and every 6 months thereafter for 10 years.

Antinociceptive effect of intrathecal P7C3 via GABA in a rat model of inflammatory pain.

The recently identified molecule P7C3 has been highlighted in the field of pain research. We examined the effect of intrathecal P7C3 in tissue injury pain evoked by formalin injection and determined the role of the GABA system in the activity of P7C3 at the spinal level. Male Sprague-Dawley rats with intrathecal catheters implanted for experimental drug delivery were studied.

Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement.

A gold(I)-catalyzed enantioselective thioallylation of propiolates with allyl sulfides is described. The key mechanistic element is a sulfonium-induced Claisen rearrangement which helps minimize the allyl dissociation and render higher enantioselectivity. This protocol features remarkable scope of the allyl moiety, allowing enantiocontrolled synthesis of all-carbon quaternary centers, and exhibits exceptional functional group compatibility with many Lewis bases and π-bonds.

Structures of the Skin Microbiome and Mycobiome Depending on Skin Sensitivity.

Sensitive skin (SS) syndrome is a globally widespread, self-diagnosed discomfort characterized by subjective complaints. Although the skin microbiome is considered important in skin health, the relationship between the skin microbiome and skin sensitivity is still unknown. Here, we aimed to (i) investigate whether the microbiome and mycobiome of SS are distinct from those of non-sensitive skin (NS), and (ii) define the characteristics of the skin microbiome associated with skin sensitivity.

Synthesis of γ-substituted carbonyl compounds from DMSO-mediated oxidation of enynamides: mechanistic insights and carbon- and hetero-functionalizations.

Oxidative coupling of 1,3-enynamides using DMSO as a terminal oxidant has been developed. Carbon as well as unmodified heteroatom nucleophiles, including aliphatic alcohols, thiols, and hydrazides, could be efficiently alkylated at the γ-position in a highly regioselective fashion. The kinetic analysis suggested a nucleophile-dependent mechanism ranging from a concerted S2'' to a carbocationic mechanism.

Segregation of age-related skin microbiome characteristics by functionality.

Although physiological changes are the most evident indicators of skin aging by alteration of the skin's structure and function, we question whether skin aging is also affected by the structure and assembly process of the skin microbiome. We analysed the skin microbiomes of 73 healthy Chinese women in two age groups (25-35 years old and 56-63 years old) using 16S rRNA gene amplicon sequencing; the overall microbiome structure was significantly different between the two age groups. An analysis using ecological theory to evaluate the process of microbial community assembly processes revealed that the microbiomes of the older group were formed under a greater influence of the niche-based process, with the network of microbes being more collapsed than that of the younger group.

MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma.

15-hydroxyprostaglandin dehydrogenase (15-PGDH), the rate-limiting enzyme in prostaglandin E2 degradation, is decreased in gastric cancers and microRNA (miR)-21 is one of the regulators. We investigated the expression and regulation of 15-PGDH in eary gastric carcinogenesis utilizing endoscopic submucosal dissection (ESD) and gastric cancer cell lines. Expression of 15-PGDH and cyclooxygenase-2 as well as the promoter methylation of 15-PGDH were evaluted.

Asymmetric Synthesis of Dihydropyranones via Gold(I)-Catalyzed Intermolecular [4+2] Annulation of Propiolates and Alkenes.

Intermolecular asymmetric gold catalysis involving alkyne activation presents a significant challenge due to its distinct mechanistic mode from other metals. Herein, we report a highly enantioselective synthesis of α,β-unsaturated δ-lactones from [4+2] annulation of propiolates and alkenes in upto 95 % ee. Notably, for the desired chiral recognition, the choice of 1,1,2,2-tetrachloroethane as solvent was found to be crucial.

Endoscopic Transplantation of Mesenchymal Stem Cell Sheets in Experimental Colitis in Rats.

Owing to the recent progress in regenerative medicine technology, clinical trials that harnessed the regeneration and immune modulation potentiality of stem cells for treating IBD have shown promising results. We investigated the feasibility and utility of intraluminal endoscopic transplantation of rat MSC sheets in murine models of experimental colitis for targeted delivery of stem cells to lesions. We isolated adipose-derived mesenchymal stem cells (AD-MSC) and bone marrow-derived mesenchymal stem cells (BM-MSC) from EGFP-transgenic rats and fabricated the cells in sheet forms using temperature-responsive culture dishes.

Fragile skin microbiomes in megacities are assembled by a predominantly niche-based process.

Given the higher incidence of skin diseases in more urbanized populations and its association with the skin microbiome, we questioned how the skin microbiome differed depending on the degree of urbanization. Skin microbiomes of 231 healthy subjects in five large cities in China varied mainly with environment and socioeconomic status of the cities in question. The differences among microbiomes could be explained by the predominantly niche-based assembly of microbial communities, which was supported by a dominance test, β-null deviation, and edge-length abundance distribution.

Hippo-mediated suppression of IRS2/AKT signaling prevents hepatic steatosis and liver cancer.

Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for liver cancer; therefore, its prevention is an important clinical goal. Ablation of phosphatase and tensin homolog (PTEN) or the protein kinase Hippo signaling pathway induces liver cancer via activation of AKT or the transcriptional regulators YAP/TAZ, respectively; however, the potential for crosstalk between the PTEN/AKT and Hippo/YAP/TAZ pathways in liver tumorigenesis has thus far remained unclear. Here, we have shown that deletion of both PTEN and SAV1 in the liver accelerates the development of NAFLD and liver cancer in mice.

Clinical implications of the Hippo-YAP pathway in multiple cancer contexts.

The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers.

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

Mycolactone, a polyketide molecule produced by , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts.

Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma.

Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients.

Sinomenine produces peripheral analgesic effects via inhibition of voltage-gated sodium currents.

Sinomenium acutum has been used in traditional medicine to treat a painful disease such as rheumatic arthritis and neuralgia. Sinomenine, which is a main bioactive ingredient in Sinomenium acutum, has been reported to have an analgesic effect in diverse pain animal models. However little is known about the detailed mechanisms underlying peripheral analgesic effect of sinomenine.

Brønsted Acid Catalyzed Oxygenative Bimolecular Friedel-Crafts-type Coupling of Ynamides.

A non-metal approach for accessing α-oxo carbene surrogates for a C-C bond-forming bimolecular coupling between ynamides and nucleophilic arenes was developed. This acid-catalyzed coupling features mild temperature, which is critical for the required temporal chemoselectivity among nucleophiles. The scope of nucleophiles includes indoles, pyrroles, anilines, phenols and silyl enolethers.

Prostaglandin E Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice.

Background & Aims: Prostaglandin E (PGE) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE signaling pathway that contribute to tumor formation. We investigated whether yes-associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE function.

The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis.

Renal tubulointerstitial fibrosis (TIF) is the final pathway of various renal injuries that result in chronic kidney disease. The mammalian Hippo-Salvador signaling pathway has been implicated in the regulation of cell proliferation, cell death, tissue regeneration, and tumorigenesis. Here, we report that the Hippo-Salvador pathway plays a role in disease development in patients with TIF and in a mouse model of TIF.

Unconstrained detection of freezing of Gait in Parkinson's disease patients using smartphone.

Freezing of gait (FOG) is a common motor impairment to suffer an inability to walk, experienced by Parkinson's disease (PD) patients. FOG interferes with daily activities and increases fall risk, which can cause severe health problems. We propose a novel smartphone-based system to detect FOG symptoms in an unconstrained way.

The relative importance of performance factors in Korean archery.

This study explored the factors affecting archery performance by calculating their relative importance in Korean archery. This study used the Delphi technique and the analytic hierarchy process (AHP). After reviewing the literature and collecting data on performance factors in archery, the importance of factors affecting archery performance was calculated by holding meetings with experts (20 archery experts) and conducting confirmatory factor analysis (463 archers) and the AHP (36 archery experts).

Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism.

Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day) for 11 years.

Hippo-Foxa2 signaling pathway plays a role in peripheral lung maturation and surfactant homeostasis.

Respiratory distress syndrome (RDS), which is induced by insufficient production of surfactant, is the leading cause of mortality in preterm babies. Although several transcription factors are known to be involved in surfactant protein expression, the molecular mechanisms and signaling pathways upstream of these transcription factors have remained elusive. Here, using mammalian Hippo kinases (Mst1/2, mammalian sterile 20-like kinase 1/2) conditional knockout mice, we demonstrate that Mst1/2 kinases are critical for orchestration of transcription factors involved in surfactant protein homeostasis and prevention of RDS.