Total Synthesis of -Steroids via Cycloaddition Strategy.

ConspectusSteroids continue to play a significant role in organic chemistry, medicinal chemistry, and drug discovery due to their important biological activities and diverse intriguing structures. Although synthetic organic chemists have successfully constructed and elaborated the classical [6-6-6-5] tetracyclic steroid skeleton for nearly a century, synthesis of the unusual rearranged steroids, particularly -steroids with a medium-sized ring, remains a challenge in the synthetic community. Furthermore, the structures of -steroids are complex and diverse, containing a seven-membered ring embedded in the fused or bridged A/B ring system and possessing numerous stereogenic centers.

Asymmetric Total Synthesis of Twin Bufogargarizins A and B.

The first and asymmetric total synthesis of bufogargarizins A and B, two unusual and highly oxygenated twin steroids with rearranged A/B rings, was achieved. The synthetically challenging [7-5-6-5] tetracyclic ring system of bufogargarizin A was efficiently constructed by the first intramolecular Ru-catalyzed [5 + 2] cycloaddition reaction of a vinyl ether cyclopropane-yne. Notably, the interesting [5-7-6-5] tetracyclic skeleton of bufogargarizin B was diastereoselectively reassembled by unique retro-aldol/transannular aldol cascade reactions from the [7-5-6-5] tetracyclic framework.

Analysis of N6-Methyladenosine RNA Methylation Regulators in Diagnosis and Distinct Molecular Subtypes of Ankylosing Spondylitis.

The most frequent internal modification in eukaryotic mRNA is N6-methyladenosine (m6A). However, what we know about the m6A regulators in Ankylosing spondylitis (AS) is still limited. In our study, eight distinct m6A regulators were selected utilizing Differentially Expressed Gene (DEG) analysis of the Gene Expression Omnibus GSE73754 dataset for making comparisons between AS (Ankylosing spondylitis) and non-AS patients.

Targeting neuropilin-1 interactions is a promising anti-tumor strategy.

Neuropilins (NRP1 and NRP2) are multifunctional receptor proteins that are involved in nerve, blood vessel, and tumor development. NRP1 was first found to be expressed in neurons, but subsequent studies have demonstrated its surface expression in cells from the endothelium and lymph nodes. NRP1 has been demonstrated to be involved in the occurrence and development of a variety of cancers.

Asymmetric Total Synthesis of Bufospirostenin A.

The first and asymmetric total synthesis of bioactive bufospirostenin A, an unusual spirostanol with rearranged A/B rings, was accomplished. The synthetically challenging [5-7-6-5] tetracyclic ring system, found in bufospirostenin A and some other natural products, was efficiently constructed by the unique intramolecular rhodium-catalyzed Pauson-Khand reaction of an alkoxyallene-yne. The 11 stereocenters in the final product, including the 10 contiguous stereocenters, were installed diastereoselectively.

Unusual KIE and dynamics effects in the Fe-catalyzed hetero-Diels-Alder reaction of unactivated aldehydes and dienes.

Hetero-Diels-Alder (HDA) reaction is an important synthetic method for many natural products. An iron(III) catalyst was developed to catalyze the challenging HDA reaction of unactivated aldehydes and dienes with high selectivity. Here we report extensive density-functional theory (DFT) calculations and molecular dynamics simulations that show effects of iron (including its coordinate mode and/or spin state) on the dynamics of this reaction: considerably enhancing dynamically stepwise process, broadening entrance channel and narrowing exit channel from concerted asynchronous transition states.

Application of Newcastle disease virus in the treatment of colorectal cancer.

Colorectal cancer (CRC) is one of the main reasons of tumor-related deaths worldwide. At present, the main treatment is surgery, but the results are unsatisfactory, and the prognosis is poor. The majority of patients die due to liver or lung metastasis or recurrence.

Screening of aptamers and their potential application in targeted diagnosis and therapy of liver cancer.

Aptamers are a class of single oligonucleotide molecules (DNA or RNA) that are screened from random DNA or RNA oligonucleotide chain libraries by the systemic evolution of ligands by exponential enrichment technology. The selected aptamers are capable of specifically binding to different targeting molecules, which is achieved by the three-dimensional structure of aptamers. Aptamers are similar in function to monoclonal antibodies, and therefore, they are also referred to as "chemical antibodies".

Isolation, Structure Elucidation, and Total Synthesis of Myrtuspirone A from Myrtus communis.

A pair of enantiomeric triketone-phloroglucinol hybrids, (+)- and (-)-myrtuspirone A (1), featuring an unprecedented 3-isopropyl-3 H-spiro[benzofuran-2,1'-cyclohexane] backbone, were isolated from the leaves of Myrtus communis. The absolute configuration of each enantiomer of 1 was determined by X-ray diffraction and chemical calculations. Furthermore, the gram-scale total syntheses of (±)-1 and (-)-1 were conducted in four steps using a Michael- N-iodosuccinimide (NIS)-mediated (3 + 2)-annulation reaction.

APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production.

The adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC) but remains a challenge for drug development. Long noncoding RNAs (lncRNAs) are invaluable in identifying cancer pathologies and providing therapeutic options for patients with cancer. Here, we identified a lncRNA (lncRNA-APC1) activated by APC through lncRNA microarray screening and examined its expression in a large cohort of CRC tissues.

Catalytic asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E.

Herein, we describe a concise catalytic approach to the first asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E. The syntheses proceed in only 5-7 steps from the readily available compound , without the need for protecting groups. Key features of the syntheses include a unique organocatalytic asymmetric Friedel-Crafts-type Michael addition with high enantioselectivity and a broad substrate scope, a novel Michael-ketalization-annulation cascade reaction, and an oxidative [3 + 2] cycloaddition.

Efficacy and safety of thrombopoietin receptor agonists in children with chronic immune thrombocytopenia: a meta-analysis.

Background And Aim: Thrombopoietin receptor agonists (TPO-RAs) have been shown to be safe and effective for adults with chronic immune thrombocytopenia (ITP). The aim of this meta-analysis is to assess the efficacy and safety of thrombopoietin receptor agonists for children with chronic ITP.

Materials And Methods: Clinical randomized controlled trials (RCTs) evaluating the efficacy and safety of TPO-RAs in pediatric ITP patients published up to June 2017 were retrieved from PubMed, Cochrane Library, and Embase databases.

[Effect of Kangxianling Recipe on p38MAPK/NF-KBp65 Mediated Inflammatory Factors in 5/6 Nephrectomized Mice].

Objective To observe effects of Kangxianling Recipe ( KXLR) on p38MAPK/NF- κBp65 mediated inflammatory factors in chronic renal failure ( CRF) model mice. Methods Totally 56 C57BL/6J male mice (18 -22 g) were recruited in this experiment. Ten were randomly selected as a sham-operation group.

[Protective effect and underlying mechanism of cordycepin on non-alcoholic fatty liver in ob/ob mice].

This study is designed to investigate the protective effect and mechanism of cordycepin on non- alcoholic fatty liver in ob/ob mice. Twelve-week-old male ob/ob mice were divided into 5 groups according to their body weight and blood glucose, and C57BL/6J mice were used in the control group. The animals were orally administered with cordycepin for 7 weeks.

[Antifungal azoles exacerbate vinblastine-related hyponatremia in ALL children].

The purpose of this study was to investigate the clinical characteristics and the treatments of patients with vinblastine-related hyponatremia which was aggravated by azole antifungal agents in children with acute lymphoblastic leukemia(ALL). A total of 93 children treated with vinblastine in our department during April 2013 to March 2014 were enrolled in this study and were divided into 3 groups:VDLD, VDLD with azoles antifungal, VDLD with non azoles antifungal. The incidence and severity of hyponatremia were statistically analysed.

Impulse oscillometry for leukotriene D4 inhalation challenge in asthma.

Background: The value of impulse oscillometry (IOS) for bronchial provocation testing is poorly defined. We investigated the positive threshold derived from the parameters and diagnostic power of IOS for asthma with the leukotriene D(4) bronchial provocation test.

Methods: We enrolled 62 subjects with asthma and 21 healthy subjects.

[Pulmonary function of children with right lung middle lobe syndrome].

Objective: To study the changes of pulmonary function in children with right lung middle lobe syndrome before and after treatment.

Methods: Thirty children with right lung middle lobe syndrome were classified into two age groups: < or =4 years old and >4 years old. Pulmonary function was tested by the 2600-type and the MIR-type pulmonary function spirometry in the < or =4 years and the >4 years age groups, respectively before and after treatment.

A novel process for production of hepatitis A virus in Vero cells grown on microcarriers in bioreactor.

Aim: To develop a novel process for production of HAV in Vero cells grown on microcarriers in a bioreactor.

Methods: Vero cells infected with HAV strain W were seeded at an initial density of 1 x 10(5) cells/mL into a 7-L bioreactor containing Cytodex-I microcarriers. During the stage of cell proliferation, the following conditions were applied: pH 7.