Palladium-catalyzed cascade cyclization of isocyanides with di-(-iodophenyl)sulfonylguanidines: access to heterocyclic fused quinazolines.

A palladium-catalyzed cascade cyclization reaction of di--iodophenyl sulfonylguanidines with isocyanides for the efficient and selective synthesis of 5- or 6-membered heterocyclic fused quinazolines has been developed. Diverse functional groups are well tolerated, and this method has been successfully applied to a larger scale synthesis.

Radical-Initiated Dearomative Annulation of Tryptamine-Derived Isocyanides: Selective Synthesis of CF-Substituted β-Aza-spiroindolines and β-Carbolines.

A mild approach for synthesizing CF-substituted β-aza-spiroindolines and β-carbolines from tryptamine-derived isocyanides via site-selective radical annulations has been reported. The crucial role of C2 substituents in the selective annulation process has been clarified. The approach shows good generality and practical applicability, highlighting its effectiveness and versatility.

High-resolution yeast actin structures indicate the molecular mechanism of actin filament stiffening by cations.

Actin filament assembly and the regulation of its mechanical properties are fundamental processes essential for eukaryotic cell function. Residue E167 in vertebrate actins forms an inter-subunit salt bridge with residue K61 of the adjacent subunit. Saccharomyces cerevisiae actin filaments are more flexible than vertebrate filaments and have an alanine at this position (A167).

CryoEM Workflow Acceleration with Feret Signatures.

Common challenges in cryogenic electron microscopy, such as orientation bias, conformational diversity, and 3D misclassification, complicate single particle analysis and lead to significant resource expenditure. We previously introduced an in silico method using the maximum Feret diameter distribution, the Feret signature, to characterize sample heterogeneity of disc-shaped samples. Here, we expanded the Feret signature methodology to identify preferred orientations of samples containing arbitrary shapes with only about 1000 particles required.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective non-comparative study.

Aim: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients.

Methods: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo.

Precise Synthesis of Diastereomers of Spiro-oxindole Derivatives through Dynamic Covalent Transformation.

In this study, [1+2+2] cyclization of tryptamine-derived isocyanides with 3-ylideneoxindoles was systematically investigated. A series of structurally complex spiro-oxindole derivatives were obtained. Characteristic dynamic covalent chemistry was observed and confirmed by experiments and density functional theory calculation.

Adequate nutrient intake mitigate the toxic effects of bromate on the rotifer Brachionus calyciflorus.

Bromate is receiving increased attention as a typical disinfection by-product in aquatic environments, but bromate toxicity tests on invertebrate such as Brachionus calyciflorus rotifer are inadequate. In the present study, the long-term toxicity tests on B. calyciflorus were performed during 21 days under the exposure of different bromate concentrations and two algal density conditions.

Integrated Metabolomic and Transcriptomic Analyses Reveal the Potential Regulation of Flavonoids in the Production of Embryogenic Cultures during Early Somatic Embryogenesis of Longan ( Lour.).

Embryogenic cultures of longan ( Lour.) contain various metabolites with pharmacological properties that may function in the regulation of somatic embryogenesis (SE). In this study, based on widely targeted metabolomics, 501 metabolites were obtained from the embryogenic calli, incomplete compact proembryogenic cultures, and globular embryos during early SE of longan, among which 41 flavonoids were differentially accumulated during the SE.

Risk factors for lower extremity deep vein thrombosis in acute stroke patients following endovascular thrombectomy: a retrospective cohort study.

Background: Deep vein thrombosis (DVT) in lower extremities as a common complication of acute ischemic stroke (AIS) has long been studied. However, as the therapeutic options for AIS continue to advance, the pathogenic mechanisms behind DVT may change. Endovascular thrombectomy (EVT) has replaced intravenous thrombolysis and become the preferred treatment for AIS patients with large vessel occlusions.

Coupling-Spirocyclization Cascade of Tryptamine-Derived Isocyanides with Iodonium Ylides and Despirocyclization Reactions.

A cobalt(II)-catalyzed coupling-cyclization cascade reaction between tryptamine-derived isocyanides and iodonium ylides is investigated, which allowed for the synthesis of different types of spiroindoline compounds by variation of substituents at the N1- and C2-positions in the indole skeleton. More interesting is that the spiroindoline products could undergo despirocyclization in the presence of amines, enabling efficient construction of enamine compounds.

Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease.

Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease. As a result of the interaction between the liver and the gut microbiota, bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption. With the development of genomics and metabolomics, more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors.

Clinical application of a modified predeposit autologous red blood cell apheresis in multistage spinal fusion: a single-center retrospective study.

Purpose: This study aimed to evaluate the efficacy and safety of predeposit autologous RBC apheresis (PARA) in patients undergoing multilevel spinal fusion surgery.

Methods: A total of 112 patients from January 2020 to June 2022 were divided into two groups according to PARA: the PARA group ( = 51) and the control group ( = 61). The baseline characteristics of the patients, outcomes, transfusion cost, hospitalization cost, length of stay, complications, and changes in hemoglobin and hematocrit levels between the two groups were compared.

NBS-induced intramolecular annulation reactions for the divergent synthesis of fused- and spirocyclic indolines.

An NBS-induced intramolecular annulation of 3-(1-indol-3-yl)--alkoxypropanamide is described. The reactions proceed well and quickly under mild conditions with the help of a base. It was found that C2-substituents on the indole ring in 3-(1-indol-3-yl)--alkoxypropanamide have a great influence upon the reaction.

Synthesis of Azoxy Compounds: from Copper Compounds to Mesoporous Silica-Encaged Ultrasmall Copper Catalysts.

Azoxy compounds have aroused extensive attention due to their unique biological activities, but the chemical synthesis of these compounds often suffers from limitations due to their requirement for stoichiometric oxidants, high costs, and restricted substrate range. Herein, a series of azoxy compounds were constructed via facile coupling reactions by using cost-effective N-methoxyformamide and nitroso compounds over Cu-based catalysts, affording high product yields with excellent tolerance of functional groups. Significantly, the mesoporous silica nanosphere-encapsulated ultrasmall Cu (Cu@MSN) catalyst was developed via a one-pot synthetic method and first used for the synthesis of azoxy compounds.

Influencing factors analysis of adaptability of cancer patients to return-to-work.

Objectives: To clarify the adaptability of cancer patients to return to work and explore its influencing factors.

Design: A cross-sectional study.

Settings/participants: From March to October 2021, 283 cancer patients in the follow-up period were recruited from the oncology departments of four secondary and above hospitals and cancer friendship associations in Nantong city using self-developed scale of adaptability to return to work for cancer patients by convenience sampling method.

Divergent Synthesis of Pentacyclic Isoindolinones Enabled by Sequential Insertion of Two Different Isocyanides and Acid Promoted Cyclization of Ketenimines.

A palladium-catalyzed multicomponent reaction involving -bromobenzaldehydes and two different isocyanides was developed to assemble series of isoindolinones with spiroindolenine or azepinoindole skeletons. This sequential insertion reaction features mild conditions, a wide substrate scope, and high efficiency. Preliminary mechanistic study indicated that the difference in steric hindrance between isocyanide components is crucial when regulating the reaction sequence, whereas the ligand also played an important role during the whole process.

MEPSi: A tool for simulating tomograms of membrane-embedded proteins.

The throughput and fidelity of cryogenic cellular electron tomography (cryo-ET) is constantly increasing through advances in cryogenic electron microscope hardware, direct electron detection devices, and powerful image processing algorithms. However, the need for careful optimization of sample preparations and for access to expensive, high-end equipment, make cryo-ET a costly and time-consuming technique. Generally, only after the last step of the cryo-ET workflow, when reconstructed tomograms are available, it becomes clear whether the chosen imaging parameters were suitable for a specific type of sample in order to answer a specific biological question.

Characterization of heterogeneity in nanodisc samples using Feret signatures.

Nanodiscs have become a popular tool in structure determination of membrane proteins using cryogenic electron microscopy and single particle analysis. However, the structure determination of small membrane proteins remains challenging. When the embedded protein is in the same size range as the nanodisc, the nanodisc can significantly contribute to the alignment and classification during the structure determination process.

Genome-wide identification of miRNAs and targets associated with cell wall biosynthesis: Differential roles of dlo-miR397a and dlo-miR408-3p during early somatic embryogenesis in longan.

The dynamic alterations in cell wall (CW) biosynthesis play an essential role in physiological isolation during the plant somatic embryogenesis (SE). However, the mechanisms underlying the functions of cell wall-associated miRNAs (CW-miRNA) remain poorly understood in plant SE. Here, we have identified 36 distinct candidate miRNAs associated with CW biosynthesis from longan third-generation genome as well as miRNA transcriptome, and modified RLM-RACE validated four distinct miRNA, which specifically targeted four CW-related genes.

-Stereoselective C3-Spirocyclization and C2-Amination of 3-(2-Isocyanoethyl)indole Using ,-Cyclic Azomethine Imines.

By utilizing an underexplored reaction mode of ,-cyclic azomethine imines, a catalyst-free [1+2+3] cycloaddition/N-N bond cleavage sequential reaction for accessing spiroindolines with -stereoselectivity was developed. On the basis of experimental results and DFT calculations, peroxide and ethereal solvent were identified to trigger the hydrogen abstraction of the unstable [1+2+3] cycloaddition adducts, followed by homolytic cleavage of the N-N bond and hydrogen absorption.

[4 + 1 + 1] Tandem Cyclization Reaction Involving Isocyanides: Access to 2-(Trifluoromethyl)quinazolin-4(3)-imines.

A palladium-catalyzed three-component reaction of isocyanides, 2,2,2-trifluoro--(2-iodophenyl)acetimidoyl chlorides, and amines for the one-pot synthesis of 2-(trifluoromethyl)quinazolin-4(3)-imines was described. The protocol features a wide substrate scope, high efficiency, and readily available raw materials.

Divergent Reaction of Isocyanides with -Bromobenzaldehydes: Synthesis of Ketenimines and Lactams with Isoindolinone Cores.

A divergent reaction of isocyanides with -bromobenzaldehydes for the synthesis of isoindolinone-derived ketenimines and lactams was disclosed. The reaction features readily available reactants, relatively mild conditions, and high yields of products. Ketenimines could be applied in further transformations for access to other functional molecules.

Cascade Reaction of Tryptamine-Derived Isocyanides with Nitrile Oxides: Construction of Oxazine Fused-Spiroindoline Derivatives.

A one-step cascade reaction of tryptamine-derived isocyanides with generated nitrile oxides for the synthesis of fused spiroindolines was described. The desired products could be efficiently synthesized in moderate to good yields (42-87%). The protocol features mild conditions, wide substrate scope, and high efficiency.

Cobalt-Catalyzed Isocyanide-Based Three-Component Cascade for the Synthesis of Quinazolines.

A Co-catalyzed cyclization reaction of isocyanides, azides, and amines to access quinazoline derivatives was described. This protocol features a high atom economy, mild reaction conditions, excellent yields, and a broad substrate scope. This cascade reaction involved three or four C-N bonds and the formation of one or two rings.

The actomyosin interface contains an evolutionary conserved core and an ancillary interface involved in specificity.

Plasmodium falciparum, the causative agent of malaria, moves by an atypical process called gliding motility. Actomyosin interactions are central to gliding motility. However, the details of these interactions remained elusive until now.