Galvanic Cell-Stimulated Mesenchymal Stem Cell Mesh for Enhanced Pelvic Organ Prolapse Treatment.

Implantation of a mesh loaded with mesenchymal stem cells (MSCs) is a common approach for the treatment of pelvic organ prolapse (POP). The mesh provides effective support to pelvic floor, enhancing muscle contraction of pelvic organs while reducing inflammation. In this study, a fully degradable mesh is designed for the treatment of POP, utilizing MSCs stimulated by a galvanic battery-powered electric field.

Organocatalytic diastereo- and atropo-selective construction of eight-membered bridged (hetero)biaryls asymmetric intramolecular [3 + 2] cycloaddition.

An unprecedented and straightforward route for the asymmetric construction of privileged atroposelective bridged (hetero)biaryl eight-membered scaffolds has been accomplished through chiral phosphoric acid catalyzed asymmetric intramolecular [3 + 2] cycloaddition of innovative (hetero)biaryl aldehydes with 3-aminooxindole hydrochlorides. A class of eight-membered bridged (hetero)biaryl lactones fused to spiro[pyrrolidine-oxindole] derivatives, possessing both chiral C-C/C-N axes and multiple contiguous stereocenters, were obtained in good yields with excellent enantioselectivities and diastereoselectivities in one step through this direct strategy. In addition, the good scalability and derivatization of the title compounds demonstrated their synthetic utility.

Asymmetric synthesis of atropisomeric arylpyrazoles direct arylation of 5-aminopyrazoles with naphthoquinones.

Construction of axially chiral arylpyrazoles represents an attractive challenge due to the relatively low rotational barrier of biaryl structures containing five-membered heterocycles. This work describes the catalytic asymmetric construction of axially chiral arylpyrazoles using 5-aminopyrazoles and naphthoquinone derivatives. The chiral axis could be formed through a central-to-axial chirality relay step of the chiral phosphoric acid-catalyzed arylation reaction, which features excellent yields and enantioselectivities with a broad substrate scope under mild reaction conditions.

Squaramide-catalyzed asymmetric regioselective allylic alkylation of 4-aminopyrazolones with Morita-Baylis-Hillman carbonates.

An efficient squaramide-catalyzed asymmetric allylic alkylation of 4-aminopyrazolones with various MBH carbonates different pathways has been described. This method provides access to a series of pyrazolone derivatives bearing a nitrogen-containing quaternary stereocenter in high yields with excellent enantioselectivities and regioselectivities under mild conditions. In addition, we utilized the target products to construct a range of bi-heterocyclic skeletons through [3 + 2] cycloadditions.

DMAP-Catalyzed [4+3] Spiroannulation of Pyrazolone-Derived Morita-Baylis-Hillman Carbonates with -(-Chloromethyl)aryl Amides to Forge Spiro[pyrazolone-azepine] Scaffolds.

A novel DMAP-catalyzed [4+3] spiroannulation of pyrazolone-derived Morita-Baylis-Hillman carbonates with -(-chloromethyl)aryl amides was developed. This reaction led to the assembly of medicinally relevant pyrazolone and azepine nuclei into a structurally new spirocyclic scaffold, and a diverse array of spiro[pyrazolone-azepine] products were afforded in good to excellent yields (up to 93%) with a wide substrate scope (23 examples) under mild conditions. Moreover, a gram-scale reaction and product transformations were conducted, which further increased the diversity of products.

Desymmetrization of Prochiral -Pyrazolyl Maleimides via Organocatalyzed Asymmetric Michael Addition with Pyrazolones: Construction of Tri--Heterocyclic Scaffolds Bearing Both Central and Axial Chirality.

The desymmetrization of -pyrazolyl maleimides was realized through an asymmetric Michael addition by using pyrazolones under mild conditions, leading to the formation of a tri--heterocyclic pyrazole-succinimide-pyrazolone assembly in high yields with excellent enantioselectivities (up to 99% yield, up to 99% ee). The use of a quinine-derived thiourea catalyst was essential for achieving stereocontrol of the vicinal quaternary-tertiary stereocenters together with the C-N chiral axis. Salient features of this protocol included a broad substrate scope, atom economy, mild conditions and simple operation.

Palladium-Catalyzed Stereoselective Construction of 1,3-Stereocenters Displaying Axial and Central Chirality via Asymmetric Alkylations.

The concurrent construction of 1,3-stereocenters remains a challenge. Herein, we report the development of stereoselective union of a point chiral center with allenyl axial chirality in 1,3-position by Pd-catalyzed asymmetric allenylic alkylation between racemic allenyl carbonates and indanone-derived β-ketoesters. Various target products bearing a broad range of functional groups were afforded in high yield (up to 99%) with excellent enantioselectivities (up to 98% ee) and good diastereoselectivities (up to 13:1 dr).

Asymmetric [3+2] spiroannulation of pyrazolone-derived Morita-Baylis-Hillman carbonates with alkynyl ketones: facile access to spiro[cyclopentadiene-pyrazolone] scaffolds.

A tertiary amine-catalyzed asymmetric [3+2] spiroannulation reaction of pyrazolone-derived Morita-Baylis-Hillman carbonates with alkynyl ketones was achieved under mild conditions. This protocol offers a facile approach to chiral spiro[cyclopentadiene-pyrazolone] scaffolds in good to high yields (up to 92%) with good degrees of enantiocontrol (up to 98% ee). In addition, scale-up reaction and transformation of the products were performed to show the synthetic utility of this protocol.

C-4 benzofuranylation of pyrazolones by a metal-free catalyzed indirect heteroarylation strategy.

A metal-free catalyzed indirect heteroarylation of pyrazolones with 2-(3-hydroxy-3,3-diarylprop-1-yn-1-yl) phenols has been developed, and a series of novel 4-benzofuranyl substituted pyrazolone derivatives were obtained in moderate to excellent yields (up to 90%). The process has the salient features of metal-free catalysis, operational simplicity, good substrate compatibility and mild reaction conditions. In particular, the integration of the pyrazolone skeleton and benzofuran scaffold into a single molecule is expected to be of potential interest for medicinal research.

Construction of a spiro[pyrazolone-4,2'-pyridoindole] scaffold a [3 + 3] cycloaddition of 2-indolylmethanol with a 4-aminopyrazolone-derived azomethine ylide.

This work reports a facile [3 + 3] cycloaddition sequence of two important heterocyclic pharmacophores, pyrazolone and 2-indolylmethanol, integrated into a polycyclic hybrid scaffold. In this process, an generated azomethine ylide obtained from 4-aminopyrazolone and benzaldehyde reacts with 2-indolylmethanols to offer spiro[pyrazolone-pyridoindole] scaffolds in high yields with excellent diastereoselectivities. Remarkably, the reaction is carried out at room temperature without any catalyst and base.

The effect and prediction of diurnal temperature range in high altitude area on outpatient and emergency room admissions for cardiovascular diseases.

Purpose: Diurnal temperature range (DTR) is a meteorological indicator closely associated with global climate change. Thus, we aim to explore the effects of DTR on the outpatient and emergency room (O&ER) admissions for cardiovascular diseases (CVDs), and related predictive research.

Methods: The O&ER admissions data for CVDs from three general hospitals in Jinchang of Gansu Province were collected from 2013 to 2016.

An effect of 24-hour temperature change on outpatient and emergency and inpatient visits for cardiovascular diseases in northwest China.

Some studies suggested that 24-h temperature change (TC24) was one of the potential risk factors for human health. However, evidence of the short-term effect of TC24 on outpatient and emergency department (O&ED) visits and hospitalizations for cause-specific cardiovascular diseases (CVDs) is still limited. The aim of this study is to explore the short-term effects of TC24 on O&ED visits and hospitalizations for CVDs in northwest China which is an area with large temperature variation.

Corticosteroids Improve Renal Survival: A Retrospective Analysis From Chinese Patients With Early-Stage IgA Nephropathy.

The efficacy and safety of corticosteroids and immunosuppressive therapy remain controversial for the treatment of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the effects of corticosteroid and immunosuppressant therapy in Chinese patients with early-stage IgAN whose estimated glomerular filtration rate (eGFR) was ≥45 ml/min/1.73 m and proteinuria was ≥1 g/24 h at biopsy.