Exosomes secreted from M2-polarized macrophages inhibit osteoclast differentiation via CYLD.

Objective: Bone resorption mediated by osteoclast differentiation induces the occurrence of bone-related diseases. Macrophages, an origin of osteoclasts, whose M2 type can reduce inflammation-induced bone damage. We aimed to investigate the effect of M2 macrophage-derived exosomes on osteoclast formation and elucidate its underlying mechanism.

Conformational Locking Induced Enantioselective Diarylcarbene Insertion into B-H and O-H Bonds Using a Cationic Rh(I)/Diene Catalyst.

Transition-metal-catalyzed enantioselective transformations of aryl/aryl carbene are inherently challenging due to the difficulty in distinguishing between two arene rings in the reaction process thus remain largely less explored. The few successful examples reported so far, without exception, have all been catalyzed by Rh(II)-complexes. Herein, we describe our successful development of a novel cationic Rh(I)/chiral diene catalytic system capable of efficient enantioselective B-H and O-H insertions with diaryl diazomethanes, allowing the access to a broad range of gem-diarylmethine boranes and gem-diarylmethine ethers in good yields with high enantioselectivities.

Design of a Coumarin-Based Fluorescent Probe for Efficient Imaging of Amyloid-β Plaques.

Amyloid-β (Aβ) is the core constituent protein of senile plaques, which is one of the key pathological hallmarks of Alzheimer's disease (AD). Here we describe the design, synthesis, and evaluation of coumarin-derived small molecule fluorophores for Aβ imaging. By embedding the aromatic coumarin framework into π bridge of a push-pull chromophore, a novel fluorescence probe applicable to efficient Aβ recognition was discovered.

Rhodium(I)-Catalyzed Direct Enantioselective C-H Functionalization of Indoles.

A highly regiospecific vinylogous carbene insertion protocol for direct asymmetric C-H functionalization of indoles with arylvinyldiazoacetates has been developed. Under the catalysis of simple Rh(I)/chiral diene complexes, the reaction occurs solely at the vinylogous position of the vinylcarbenoid with exceptional selectivity and enantiocontrol. It provides an efficient way to obtain an interesting class of chiral indole scaffolds bearing an α,β-unsaturated ester unit and a -diaryl carbon stereocenter in good yields (≤99%) with excellent enantioselectivities (≤96%) at room temperature.

Low Coordination State Rh -Complex as High Performance Catalyst for Asymmetric Intramolecular Cyclopropanation: Construction of penta-Substituted Cyclopropanes.

A simple, broad-scope rhodium(I)/chiral diene catalytic system for challenging asymmetric intramolecular cyclopropanation of various tri-substituted allylic diazoacetates was successfully developed. The low coordination state Rh -complex exhibits an extraordinarily high degree of tolerance to the variation in the extent of substitution of the allyl double bond, thus allowing the efficient construction of a wide range of penta-substituted, fused-ring cyclopropanes bearing three contiguous stereogenic centers, including two quaternary carbon stereocenters, in a highly enantioselective manner with ease at catalyst loading as low as 0.1 mol %.

Rhodium-Catalyzed Asymmetric 1,4-Addition of α/β-(-Indolyl) Acrylates.

A rhodium-catalyzed asymmetric 1,4-addition of -(-indolyl) acrylates to access highly enantioenriched chiral -alkylindoles promoted by chiral diene or sulfur-olefin ligands under mild reaction conditions has been developed, which provides an efficient and practical approach for constructing carbon stereocenters adjacent to the indole nitrogen. The reaction can be applied to various -indolyl-substituted -unstaturated esters and arylboron reagents, providing access to a wide range of α- and β-(-indolyl) propionate derivatives in high yields with excellent enantioselectivities (≤99% ee).

Rhodium(I) Carbene-Promoted Enantioselective C-H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights.

A rhodium(I)-diene catalyzed highly enantioselective C(sp )-H functionalization of simple unprotected indoles, pyrroles, and their common analogues such as furans, thiophenes, and benzofurans with arylvinyldiazoesters has been developed for the first time. This transformation features unusual site-selectivity exclusively at the vinyl terminus of arylvinylcarbene and enables a reliable and rapid synthetic protocol to access a distinctive class of diarylmethine-bearing α,β-unsaturated esters containing a one or two heteroarene-attached tertiary carbon stereocenter in high yields and excellent enantioselectivities under mild reaction conditions. Mechanistic studies and DFT calculations suggest that, compared to the aniline substrate, the more electron-rich indole substrate lowers the C-C addition barrier and alters the rate-determining step to the reductive elimination, leading to different isotope effect.

CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage.

Aims: Subarachnoid hemorrhage (SAH) is a devastating stroke subtype. Following SAH, erythrocyte lysis contributes to cell death and brain injuries. Blockage of the anti-phagocytic receptor Cluster of Differentiation 47 (CD47) enhances phagocyte clearance of erythrocytes, though it has not been well-studied post-SAH.

Stereodivergent Synthesis of Enantioenriched 2,3-Disubstituted Dihydrobenzofurans via a One-Pot C-H Functionalization/Oxa-Michael Addition Cascade.

A one-pot rhodium-catalyzed C-H functionalization/organocatalyzed oxa-Michael addition cascade reaction has been developed. This methodology enables the stereodivergent synthesis of diverse 2,3-disubstituted dihydrobenzofurans with broad functional group compatibility in good yields with high levels of stereoselectivity under exceptionally mild conditions. The full complement of stereoisomers of chiral 2,3-disubstituted dihydrobenzofurans and 3,4-disubstituted isochromans could be accessed at will by appropriate permutations of the two chiral catalysts.

Regiospecific and Enantioselective Arylvinylcarbene Insertion of a C-H Bond of Aniline Derivatives Enabled by a Rh(I)-Diene Catalyst.

Asymmetric insertion of an arylvinylcarbenoid into the C-H bond for direct enantioselective C(sp)-H functionalization of aniline derivatives catalyzed by a rhodium(I)-diene complex was developed for the first time. The reaction occurred exclusively at the uncommon vinyl terminus site with excellent E selectivity and enantioselectivities, providing various chiral γ,γ--diarylsubstituted α,β-unsaturated esters with broad functional group compatibility under simple and mild conditions. It provides a rare example of the asymmetric C-H insertion of arenes with selective vinylogous reactivity.

Water as a Direct Proton Source for Asymmetric Hydroarylation Catalyzed by a Rh(I)-Diene: Access to Nonproteinogenic β/γ/δ-Amino Acid Derivatives.

A highly enantioselective rhodium-catalyzed intermolecular hydroarylation of α-aminoalkyl acrylates using water as a direct proton source has been realized by employing a chiral bicyclo[3.3.0] diene ligand, allowing efficient access to a broad range of α-aryl-methyl-substituted β-, γ-, and δ-amino esters with excellent enantioselectivities (up to 98% ee) under exceptionally mild conditions.

Comparision of Mechanical Thrombectomy With Contact Aspiration or Stent Retriever in Patients With Large-vessel Occlusion in Acute Ischemic Stroke.

Objectives: Whether the direct aspiration approach of thrombectomy for recanalization in patients with acute ischemic stroke has a similar efficacy and safety compared to the stent-retriever still remains uncertain.

Methods: A retrospective data analysis was performed to identify patients with large cerebral artery acute ischemic stroke treated with endovascular thrombectomy. The study was conducted between January 2018 and December 2019 in a single stroke center.

Clinical study of different doses of atorvastatin combined with febuxostat in patients with gout and carotid atherosclerosis.

Objective: To evaluate the efficacy of atorvastatin combined with febuxostat in the treatment of gout patients with carotid atherosclerosis and to observe the effects on serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and C-reactive protein (CRP) levels, carotid plaques, and the adverse reactions.

Methods: Seventy patients with gout and carotid atherosclerosis admitted to Affiliated Hospital of Hebei University from January 2014 to June 2017 were randomly divided into a treatment group and a control group. The treatment group received oral febuxostat 40 mg/day combined with atorvastatin 40 mg/day.

Development of Bisindole-Substituted Aminopyrazoles as Novel GSK-3β Inhibitors with Suppressive Effects against Microglial Inflammation and Oxidative Neurotoxicity.

Development of glycogen synthase kinase-3β (GSK-3β) inactivation-centric agents with polypharmacological profiles is increasingly recognized as a promising therapeutic strategy against the multifactorial etiopathology of Alzheimer's disease (AD). In this respect, a series of disubstituted aminopyrazole derivatives were designed and synthesized as a new class of GSK-3β inhibitors. Most of these derivatives possess GSK-3β inhibitory activities with IC values in the micromolar ranges, among which bisindole-substituted aminopyrazole derivative displayed moderate GSK-3β inhibition (IC = 1.

Association of Killer Cell Immunoglobulin-like Receptor and Human Leukocyte antigen-C Genotype with HLA-B27 Associated Acute Anterior Uveitis and Idiopathic Acute Anterior Uveitis in a Chinese Han Population.

Purpose: whether killer cell immunoglobulin-like receptors () and human leukocyte antigens C ) are associated with associated acute anterior uveitis (B27AAU) and idiopathic AAU (IAAU) remains unclear.

Methods: PCR with sequence-specific primers was used to analyze genes and alleles in a Chinese Han population of 196AAU patients and 210 control subjects.

Results: The higher frequencies of and (.

Chiral diene-promoted room temperature conjugate arylation: highly enantioselective synthesis of substituted chiral phenylalanine derivatives and α,α-di(arylmethyl)acetates.

A highly enantiocontrolled room temperature rhodium-catalyzed conjugate arylation process was developed. The reaction proceeds through 1,4-addition of α-substituted acrylates followed by enantioselective protonation using a C1-symmetric chiral bicyclo[2,2,2] diene as the ligand and water as the proton source. This exceptionally simple protocol provides a reliable and practical access to structurally important phenylalanine derivatives and α,α-di(arylmethyl)acetates in high yields (up to 99%) with good to excellent ee values (up to 99%).

Combined intra-arterial chemotherapy and intravitreal melphalan for the treatment of advanced unilateral retinoblastoma.

Aim: To evaluate the efficacy and safety of combined intra-arterial chemotherapy (IAC) and intravitreal melphalan (IVM) for the treatment of advanced unilateral retinoblastoma.

Methods: This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma. All patients were initially treated with IAC combined with IVM.

Pd(II)-Catalyzed Asymmetric Annulation toward the Synthesis of 2,3-Disubstituted Chiral Indenols.

An enantioselective asymmetric annulation of 2-formylboronic acids with internal alkynes has been realized using a chiral phosphinooxazoline/palladium(II) catalyst. The reaction tolerates a variety of alkynes including the relatively inert diaryl substituted internal ones. A wide range of optically active 2,3-disubstituted indenols was afforded in high yields with good to excellent enantioselectivities (up to 99% yield and 99% ee).

Rhodium-Catalyzed Enantioselective Addition of Arylboroxines to Isatin-Derived -Boc Ketimines Using Chiral Phosphite-Olefin Ligands: Asymmetric Synthesis of 3-Aryl-3-amino-2-oxindoles.

An efficient rhodium-catalyzed enantioselective arylation of isatin-derived -Boc ketimines with arylboroxines has been developed using H-BINOL-derived phosphite-olefin as a chiral ligand. This method allows access to a broad variety of valuable tetrasubstituted 3-amino-2-oxindole derivatives in good yields (up to 98%) with excellent enantioselectivities (up to 98% ee).

Construction of Chiral 1,3-Diamines through Rhodium-Catalyzed Asymmetric Arylation of Cyclic N-Sulfonyl Imines.

A rhodium/sulfur-olefin complex catalyzed asymmetric 1,2-addition of arylboronic acids to six-membered 1,2,6-thiadiazinane 1,1-dioxide-type cyclic imines to access highly optically active sulfamides (95-99% ee) has been developed. By taking advantage of the simple functional group transformations, an interesting array of valuable chiral 1,3-diamines with different substitution patterns can be readily obtained in a highly enantioenriched manner.

Analysis of Peripheral Blood Cells' Transcriptome in Patients With Subarachnoid Hemorrhage From Ruptured Aneurysm Reveals Potential Biomarkers.

Background: Subarachnoid hemorrhage (SAH) is an uncommon disease. Considering ruptured intracranial aneurysms as the main cause of this disease and only a minority of the intracranial aneurysms will rupture sooner or later, to understand the underlying pathology or a specific gene expression profile of an impending ruptured intracranial aneurysm is of great importance.

Methods: The transcriptome in peripheral blood cells of patients with SAH from ruptured aneurysm was compared with that of control patients suffering from headaches.

Highly enantioselective synthesis of α-tertiary chiral amino acid derivatives through rhodium-catalyzed asymmetric arylation of cyclic N-sulfonyl α-ketimino esters.

By employing an easily available, exceptionally simple sulfur-olefin ligand, a highly enantioselective rhodium-catalyzed arylation of cyclic N-sulfonyl α-ketimino esters with arylboronic acids has been developed. The reaction allows facile access to a wide range of α,α-gem-diaryl substituted chiral amino esters in excellent yields with extremely high enantioselectivities (uniformly 98-99% ee). The synthetic utility of this approach was highlighted by the efficient synthesis of a series of interesting molecules including unique chiral spirocycles bearing 2,3-dihydrobenzofuran and 1H-isoindole skeletons.

Access to Spiroindolines and Spirodihydrobenzofurans via Pd-Catalyzed Domino Heck Spiroyclization through C-H Activation and Carbene Insertion.

A new palladium-catalyzed domino approach for the synthesis of attractive spirocyclic indolines and dihydrobenzofurans was developed. The reaction proceeds through a sequential intramolecular Heck spirocyclization, remote C-H activation, and diazocarbonyl carbene insertion. Various spiroindolines and spirodihydrobenzofurans containing two quartenary carbon stereocenters were readily obtained in good to excellent yields.

Rhodium-Catalyzed Enantioselective Alkenylation of Cyclic Ketimines: Synthesis of Multifunctional Chiral α,α-Disubstituted Allylic Amine Derivatives.

By employing a simple open-chain chiral phosphite-olefin ligand, a highly enantioselective rhodium-catalyzed alkenylation of 1,2,5-thiadiazole 1,1-dioxide-type cyclic ketimines with diverse vinylboronic acids was achieved under mild conditions at room temperature. This protocol provides an efficient and practical access to multifunctional α,α-disubstituted chiral allylic amines bearing quaternary stereocenters in high yields (up to 99%) with good to excellent ee's (up to 99%).

Ligand-Controlled Rhodium-Catalyzed Site-Selective Asymmetric Addition of Arylboronic Acids to α,β-Unsaturated Cyclic N-Sulfonyl Ketimines.

A site-selective rhodium-catalyzed asymmetric 1,4-/1,2-addition of arylboronic acids to challenging α,β-unsaturated cyclic ketimines was realized through a ligand-controlled strategy. By employing different chiral olefin ligands, a ligand-controlled switch in the reaction regioselectivity was attained for the first time. The reactions allow the synthesis of highly valuable α,α-disubstituted chiral allylic amines and enantioenriched 1,4-adducts.