Visible-light-promoted direct desulfurization of glycosyl thiols to access C-glycosides.

C-Glycosides are essential for the study of biological processes and the development of carbohydrate-based drugs. Despite the tremendous hurdles, glycochemists have often fantasized about the efficient, highly stereoselective synthesis of C-glycosides with the shortest steps under mild conditions. Herein, we report a desulfurative radical protocol to synthesize C-alkyl glycosides and coumarin C-glycosides under visible-light induced conditions without the need of an extra photocatalyst, in which stable and readily available glycosyl thiols that could be readily obtained from native sugars are activated in situ by pentafluoropyridine.

Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader.

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) and other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders of CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery of as a potent, selective, and orally bioavailable CDK12/13 PROTAC degrader.

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.

Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells.

Rap1A Modulates Store-Operated Calcium Entry in the Lung Endothelium: A Novel Mechanism Controlling NFAT-Mediated Vascular Inflammation and Permeability.

Background: Store-operated calcium entry mediated by STIM (stromal interaction molecule)-1-Orai1 (calcium release-activated calcium modulator 1) is essential in endothelial cell (EC) functions, affecting signaling, NFAT (nuclear factor for activated T cells)-induced transcription, and metabolic programs. While the small GTPase Rap1 (Ras-proximate-1) isoforms, including the predominant Rap1B, are known for their role in cadherin-mediated adhesion, EC deletion of Rap1A after birth uniquely disrupts lung endothelial barrier function. Here, we elucidate the specific mechanisms by which Rap1A modulates lung vascular integrity and inflammation.

Crucial time of emergency monitoring for reliable numerical pollution source identification.

The Pollution source identification (PSI) is an important issue on river water quality management especially for urban receiving water. Numerical inversion method is theoretically an effective PSI technique, which employs monitored downstream pollutant breakthrough curves to identify the pollution source. In practice, it is important to know how much monitoring data should be accumulated to provide PSI results with acceptable accuracy and uncertainty.

Novel strategy of S. mutans gcrR gene over-expression plus antibacterial dimethylaminohexadecyl methacrylate suppresses biofilm acids and reduces dental caries in rats.

Objective: Streptococcus mutans (S. mutans) is a major contributor to dental caries, with its ability to synthesize extracellular polysaccharides (EPS) and biofilms. The gcrR gene is a regulator of EPS synthesis and biofilm formation.

Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

Background: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT.

Methods: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy.

Evaluation of a Cascaded Deep Learning-based Algorithm for Prostate Lesion Detection at Biparametric MRI.

Background Multiparametric MRI (mpMRI) improves prostate cancer (PCa) detection compared with systematic biopsy, but its interpretation is prone to interreader variation, which results in performance inconsistency. Artificial intelligence (AI) models can assist in mpMRI interpretation, but large training data sets and extensive model testing are required. Purpose To evaluate a biparametric MRI AI algorithm for intraprostatic lesion detection and segmentation and to compare its performance with radiologist readings and biopsy results.

Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study.

Background: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels.

Methods: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019.

Charge-Transfer-Induced Interfacial Ferromagnetism in Ferromagnet-Free Oxide Heterostructures.

Due to the strong interlayer coupling between multiple degrees of freedom, oxide heterostructures have demonstrated exotic properties that are not shown by their bulk counterparts. One of the most interesting properties is ferromagnetism at the interface formed between "nonferromagnetic" compounds. Here we report on the interfacial ferromagnetic phase induced in the superlattices consisting of the two paramagnetic oxides CaRuO (CRO) and LaNiO (LNO).

Improved Detection of Target Metabolites in Brain Tumors with Intermediate TE, High SNR, and High Bandwidth Spin-Echo Sequence at 5T.

Background And Purpose: Due to high chemical shift displacement, challenges emerge at ultra-high fields when measuring metabolites using H-MRS. Our goal was to investigate how well the high SNR and high bandwidth spin-echo (HISE) technique perform at 5T for detecting target metabolites in brain tumors.

Materials And Methods: Twenty-six subjects suspected of having brain tumors were enrolled.

Genome-Wide Characterization of Differentially Expressed Scent Genes in the MEP Control Network of the Flower of Lilium 'Sorbonne'.

Fragrance is an important feature of ornamental lilies. Components of volatile substances and important genes for monoterpene synthesis in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway were examined in this study. Twenty volatile compounds (2 in the budding stage, 3 in the initial flowering stage, 7 in the semi-flowering stage, 17 in the full-flowering stage, and 5 in withering stage) were detected in the Oriental lily 'Sorbonne' using gas chromatography-mass spectrometry.

Increased long-distance and homo-trans interactions related to H3K27me3 in Arabidopsis hybrids.

In plants, the genome structure of hybrids changes compared with their parents, but the effects of these changes in hybrids remain elusive. Comparing reciprocal crosses between Col × C24 and C24 × Col in Arabidopsis using high-throughput chromosome conformation capture assay (Hi-C) analysis, we found that hybrid three-dimensional (3D) chromatin organization had more long-distance interactions relative to parents, and this was mainly located in promoter regions and enriched in genes with heterosis-related pathways. The interactions between euchromatin and heterochromatin were increased, and the compartment strength decreased in hybrids.

Deep Learning-Based Detection and Classification of Bone Lesions on Staging Computed Tomography in Prostate Cancer: A Development Study.

Rationale And Objectives: Efficiently detecting and characterizing metastatic bone lesions on staging CT is crucial for prostate cancer (PCa) care. However, it demands significant expert time and additional imaging such as PET/CT. We aimed to develop an ensemble of two automated deep learning AI models for 1) bone lesion detection and segmentation and 2) benign vs.

s^{±}-Wave Pairing and the Destructive Role of Apical-Oxygen Deficiencies in La_{3}Ni_{2}O_{7} under Pressure.

Recently, the bilayer perovskite nickelate La_{3}Ni_{2}O_{7} has been reported to show evidence of high-temperature superconductivity (SC) under a moderate pressure of about 14 GPa. To investigate the superconducting mechanism, pairing symmetry, and the role of apical-oxygen deficiencies in this material, we perform a random-phase approximation based study on a bilayer model consisting of the d_{x^{2}-y^{2}} and d_{3z^{2}-r^{2}} orbitals of Ni atoms in both the pristine crystal and the crystal with apical-oxygen deficiencies. Our analysis reveals an s^{±}-wave pairing symmetry driven by spin fluctuations.

Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.

Background: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases.

N,S coordination in Ni single-atom catalyst promoting CORR towards HCOOH.

Carbon-based single atom catalysts (SACs) are attracting extensive attention in the CO reduction reaction (CORR) due to their maximal atomic utilization, easily regulated active center and high catalytic activity, in which the coordination environment plays a crucial role in the intrinsic catalytic activity. Taking NiN as an example, this study reveals that the introduction of different numbers of S atoms into N coordination (Ni-NS ( = 1-4)) results in outstanding structural stability and catalytic activity. Owing to the additional orbitals around -1.

Global, Regional, and National Burden of Gastric Cancer in Adolescents and Young Adults, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

Introduction: Gastric cancer is a significant global health concern, ranking as the fifth most common cancer worldwide and the third leading cause of cancer-related mortality. While improvements in health awareness and medical technology have contributed to a decline in the incidence of gastric cancer in many countries, the rate of gastric cancer in adolescents and young adults (GCAYA) has shown an upward trend. Timely and effective strategies for screening, detection, and treatment are crucial for managing the burden of GCAYA and optimizing the allocation of medical resources.

Safety, tolerability, pharmacokinetics and efficacy of HB0017, a humanized monoclonal antibody that targets interleukin-17A, in healthy participants and patients with moderate-to-severe plaque psoriasis.

Background: Several interleukin (IL)-17 inhibitors have been approved for the treatment of moderate-to-severe plaque psoriasis (PsO). There is still scope for the development of affordable treatments for PsO.

Objectives: To assess, in a phase Ia study, the safety, tolerability and pharmacokinetics (PK) of HB0017, a humanized monoclonal antibody that targets IL-17A, in healthy participants and patients with moderate-to-severe plaque PsO; and, in a phase Ib study, to assess the efficacy of HB0017 in patients with moderate-to-severe plaque PsO.

Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.

Association of Procedure Time With Clinical and Procedural Outcome in Patients With Basilar Occlusion Undergoing Embolectomy.

Background And Objectives: Previous studies have demonstrated the association between the procedure time (PT) and outcomes for patients with proximal large vessel occlusion; however, whether the relationship remains for patients with acute basilar artery occlusion (ABAO) was not clear. We aimed to characterize the association between PT and other procedure-related variables on clinical outcomes among patients with ABAO who underwent endovascular treatment (EVT).

Methods: Patients with ABAO who underwent EVT with a documented PT in the EVT for Acute Basilar Artery Occlusion (BASILAR) study from January 2014 to May 2019 among 47 comprehensive centers in China were included.

Effect of Imaging Selection Paradigms on Endovascular Thrombectomy Outcomes in Patients With Acute Ischemic Stroke.

Background: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China.

Methods: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021).