Asymmetric Catalytic 1,2-Azaarene Migration to α-Azaaryl-α-Hydroxy Esters Enabled by a Tailored Ligand.

Despite their prevalence in bioactive molecules, the stereoselective construction of α-azaaryl-α-hydroxycarboxylates remains a formidable challenge. Notably, although the benzilic ester rearrangement (BER) is an efficient approach to α-hydroxycarboxylates, asymmetric catalytic BER remains poorly developed, largely due to poor stereorecognition of the vicinal diketone substituents by common chiral catalysts. In response to these issues, here we report a copper-catalyzed asymmetric BER of azaarene-derived 1,2-diketones with simple alcohols to give diverse α-azaaryl-α-hydroxy esters.

Venous return index after mechanical thrombectomy predicts parenchymal hemorrhage and poor outcomes.

Background And Purpose: The significance of early venous filling on digital subtraction angiography (DSA) after mechanical thrombectomy (MT) is unclear. This study introduces the Venous Return Index (VRI) to explore the relationship between VRI in different intracranial veins and outcomes after MT in acute anterior circulation large vessel occlusion (AC-LVO) stroke.

Methods: A retrospective analysis of AC-LVO stroke patients who underwent successful MT (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b) within 24 hours from April 2014 to March 2023 was conducted.

Switchable skeletal editing of quinolines enabled by cyclizative sequential rearrangements.

The rapid diversification of core ring structures in complex molecules through switchable skeletal editing is valuable in the drug discovery process. However, controllable methods for chemically divergent modifications of azaarene frameworks using common substrates are challenging, despite the potential to maximize structural diversity and complexity. Here we report the tunable skeletal editing of quinolines through Brønsted acid-catalysed multicomponent reactions of quinoline N-oxides, dialkyl acetylenedicarboxylates and water to generate nitrogen-containing heteroaromatic compounds together with linear compounds in a modular fashion.

Simple and Smart Metal-Phenolic Micelles for Optimizing Immunotherapy by Disrupting Tumor Stemness.

cGAS-STING pathway activation has attracted considerable attention in antitumor immunotherapy, but clinical outcomes lag behind expectations due to overlooked negative feedback mechanisms. Here, we determine that STING activation promotes tumor stemness, which weakens the efficacy of STING-based therapies, presenting a double-edged sword. To address this therapeutic paradox, a simple metal-phenolic polymeric micelle (HMQ) was developed, in which Mn (a STING agonist) is coordinated with quercetin (a stemness inhibitor) and hyaluronic acid (HA), to unlock the full therapeutic potential of the cGAS-STING pathway.

The Prognostic Significance of CTSV Expression in Patients with Hepatocellular Carcinoma.

Purpose: Cathepsin V (CTSV) is a cysteine protease peptidase, which is typically upregulated in cancer and is associated with various oncogenic processes, such as angiogenesis, proliferation, apoptosis, and invasion. The study explored the role of CTSV in hepatocellular carcinoma (HCC) and its potential as a potential biomarker.

Patients And Methods: This study collected tumor and peritumoral archived specimens from 180 HCC patients who underwent surgical resection at Zhongshan Hospital, Fudan University (Shanghai, China) between 2009 and 2010.

Enamine Acylation Enabled Desymmetrization of Malonic Esters.

Asymmetric enamine alkylation represents a powerful tool for stereoselective C-C bond formation; in contrast, the development of enantioselective enamine acylation remains elusive. Here, we report that a chiral phosphoric acid can render an in-situ-formed enamine to undergo a stereoselective intramolecular α-carbon acylation, providing an alternative approach for the synthesis of useful pyrrolinones and indolinones bearing tetrasubstituted stereocenters. Utilizing an effective integration of the desymmetrization strategy and bifunctional organocatalysis, the first example of enantioselective enamine acylation is achieved by employing readily available aminomalonic esters and cyclic ketones.

Pan-cancer analysis of prognostic and immunological role of IL4I1 in human tumors: a bulk omics research and single cell sequencing validation.

Background: Interleukin-4 inducible gene 1 (IL4I1) regulates tumor progression in numerous tumor types. However, its correlation with immune infiltration and prognosis of patients in a pan-cancer setting remains unclear.

Methods: Data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), Gene Expression Omnibus (GEO), cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource(TIMER) databases were used to evaluate IL4I1 expression, clinical features and prognostic effects, gene set enrichment, and correlation with immune cell infiltration, as well as the relationship between IL4I1 methylation and expression and survival prognosis.

Catalytic Asymmetric Cyclizative Rearrangement of Anilines and Vicinal Diketones to Access 2,2-Disubstituted Indolin-3-ones.

The efficient synthesis of chiral 2,2-disubstituted indolin-3-ones is of great importance due to its significant synthetic and biological applications. However, catalytic enantioselective methods for de novo synthesis of such heterocycles remain scarce. Herein, a novel cyclizative rearrangement of readily available anilines and vicinal diketones for the one-step construction of enantioenriched 2,2-disubstituted indolin-3-ones is presented.

Quality evaluation of natural monomer flavors for Chinese tobacco industry based on dual mode combined Fourier transform ion cyclotron resonance mass spectrometry and isotopic fine structures.

Rationale: Natural monomer flavors can modify the taste of cigarettes. However, no report was published to establish the quality control method for their chemical compositions.

Methods: In this study, licorice, a traditional natural monomer flavor used in tobacco aroma processing, was selected, and the fingerprint was developed by high-performance liquid chromatography (HPLC).

Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor-designed ZnFeO-based nanosystem.

The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFeO-based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFeO nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells.

Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown.

Objective: To assess the efficacy of argatroban for END in AIS.

Design, Setting, And Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022.

Multicomponent Cyclizative 1,2-Rearrangement Enabled Enantioselective Construction of 2,2-Disubstituted Pyrrolinones.

The 1,2-rearrangement reaction is one of the most important approaches to construct carbon-carbon bonds in organic synthesis. However, the development of catalytic asymmetric 1,2-rearrangements is still far from mature and often suffers from problems such as complex substrates, single product structure, and lack of synthetic application. Multicomponent reaction has been recognized as a robust tool for the synthesis of diverse and tunable products from readily available starting material.

Symmetrical femtosecond laser arc incision in correcting corneal astigmatism in cataract patients.

Aim: To evaluate the effect of symmetrical arc incision correcting corneal astigmatism in femtosecond laser-assisted phacoemulsification (FLACS).

Methods: This study enrolled patients with cataract combined with regular corneal astigmatism of >0.75 D, who underwent FLACS.

Catalytic Enantioselective Biltz Synthesis.

The Biltz synthesis establishes straightforward access to 5,5-disubstituted (thio)hydantoins by combining a 1,2-diketone and a (thio)urea. Its appealing features include inherent atom and step economy together with the potential to generate structurally diverse products. However, control of the stereochemistry of this reaction has proven to be a daunting challenge.

Zinc chloride-catalyzed cyclizative 1,2-rearrangement enables facile access to morpholinones bearing aza-quaternary carbons.

Morpholines and morpholinones are important building blocks in organic synthesis and pharmacophores in medicinal chemistry, however, C3-disubstituted morpholines/morpholinones are extremely difficult to access. Here we show the ZnCl-catalyzed cyclizative 1,2-rearrangement for the efficient synthesis of morpholinones bearing aza-quaternary stereocenters. A series of structurally diverse C3-disubstituted morpholin-2-ones which are difficultly accessible by existing methods were efficiently constructed from readily available two achiral linear compounds.

CA9 knockdown enhanced ionizing radiation-induced ferroptosis and radiosensitivity of hypoxic glioma cells.

Purpose: Ferroptosis is a type of regulatory cell death, caused by excessive lipid peroxidation This study aimed to explore whether ionizing radiation could induce ferroptosis in glioma cells and whether carbonic anhydrase 9 (CA9) knockdown could enhance the killing effect of ionizing radiation on hypoxic glioma cells through ferroptosis.

Materials And Methods: The protein levels of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) were detected by Western blot in glioma cells irradiated by different doses of X-ray. The relative mRNA levels of ferroptosis markers and intracellular iron-associated proteins were detected by Real-time qPCR.

Manganese facilitated cGAS-STING-IFNI pathway activation induced by ionizing radiation in glioma cells.

Purpose: After irradiation, double-stranded DNA leaked into the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, leading to the production of type I interferon (IFNI). In this study, we sought to probe the effect of ionizing radiation on activity of cGAS-STING-IFNI pathway in normoxic or hypoxic glioma cells and explore a more effective method to activate the signaling pathway, thereby activating the anti-tumor immune response and improving the therapeutic effect of radiotherapy for glioma.

Materials And Methods: Human glioma cells U251 and T98G cultured in normoxia or hypoxia (1% O) were irradiated with different doses of X-ray.

The conservative management for improving Visual Analog Scale (VAS) pain scoring in greater trochanteric pain syndrome: a Bayesian analysis.

Background: Greater trochanteric pain syndrome (GTPS) possesses a harmful influence on quality of life. Numerous conservative management modalities with varying success have been proposed for patients with GTPS. However, it is not clear which treatment is more effective for reducing pain.

Effect of gastrodin against cognitive impairment and neurodegeneration in APP/PS1 mice via regulating gut microbiota-gut-brain axis.

Gastrodin (Gas) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of Gas against cognitive impairment via regulating gut microbiota. APPswe/PSEN1dE9 transgenic (APP/PS1) mice were treated intragastrically with Gas for 4 weeks, and then cognitive deficits, deposits of amyloid-β (Aβ) and phosphorylation of tau were analyzed.

Comparative studies of hexagonal boron phosphide/VCS heterostructure and homogeneous bilayers as metal-ion battery anodes.

Heterostructures can not only maintain/avoid the desired characteristics/defects of their monolayers, but also have synergistic effects due to the contribution of an internal electric field from the heterostructure interlayer. Hexagonal boron phosphide (h-BP) and VCS were constructed into heterostructure (h-BP/VCS) and homogeneous bilayers (Dh-BP and DVCS), which were studied comparatively for their storage performances as anodes for metal (Li/Na/Mg/Ca)-ion batteries (LIBs/NIBs/MIBs/CIBs) using first-principles. The h-BP/VCS can adsorb five layers of Mg atoms while Dh-BP cannot adsorb any Mg atoms; heterostructures with a maximum adsorption concentration are stable at room temperature, while Dh-BP structures are unstable in the same cases, which make Dh-BP unsuitable as LIB/NIB/MIB/CIB anodes.

Asymmetric Construction of α,α-Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement.

An unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α-disubstituted piperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2-nitrogen shift/1,2-aryl or alkyl migration sequence, employing readily available vicinal tricarbonyl compounds and 1,2-diamines as starting materials. This approach provides an efficient access to chiral C3-disubsituted piperazin-2-ones with high enantiocontrol, which are exceedingly difficult to access from the existing synthetic methodologies.

Prevalence of HIV-1 infection among foreign applicant to residency in Shanghai, China, 2005-2016.

Shanghai is one of the largest cities in China and has the highest proportion of inbound travelers in the world. The HIV (human immunodeficiency virus) infection status of this population can reflect the global HIV epidemic trend to a certain extent. Therefore, we conducted a retrospective epidemic survey to clarify the prevalence and characteristics of HIV-1 infection among inbound travelers applying for Shanghai residency.