Schizophrenia-Related Synaptic Dysfunction and Abnormal Sensorimotor Gating in Akap11-Deficient Mice.

Background And Hypothesis: Large-scale whole exome sequencing (WES) analyses have implicated rare protein-truncating variants (PTVs) in the AKAP11 gene contributing to schizophrenia risk. Previous studies reported alterations of EEG characteristics and synaptic proteome in Akap11 mutant mice. We hypothesize that synaptic dysfunction contributes to AKAP11 deficiency in the pathogenesis of schizophrenia.

Enantioselective access to 3,3'-disubstituted oxindole derivatives by N-heterocyclic carbene catalysis.

An effectively enantioselective and regioselective N-heterocyclic carbene-catalyzed oxidative spiroannulation of isatin-derived enals with 2,4-dioxoesters to directly synthesize spirooxindole δ-lactones was realized. Subsequently, upon treatment with methanol under reflux, spirooxindole δ-lactones were effectively converted into acyclic 3,3'-disubstituted oxindole derivatives bearing an all-carbon quaternary center that might have been obtained through a novel sequence of deesterification and decarbonylation paths. This approach was qualified with a broad substrate scope and mild reaction conditions, achieving moderate to excellent yield and enantioselectivity.

Elevated NEGR1 in brain induces anxiety or depression-like phenotypes and synaptic dysfunction.

Single nucleotide polymorphisms (SNPs) within 1p31.1 region have shown significant associations with depression, and our prior functional genomics pinpointed a regulatory variant rs3101339 among them. However, its precise role in depression pathogenesis remains elusive.

The complex association of VRK2 with major depressive disorder in Han Chinese population.

Background: Major depressive disorder (MDD) is a polygenic condition with substantial heritability, with genome-wide association studies (GWAS) identifying several risk loci in European populations, including the VRK2 gene. However, the association between VRK2 and MDD in non-European populations, particularly in Han Chinese, remains underexplored.

Methods: We genotyped four VRK2 SNPs (rs2678907, rs11682175, rs1568452, rs1518395) in a cohort of 1878 MDD cases and 1800 controls of Han Chinese descent.

FeCl-Catalyzed Intermolecular Formal [8π+2σ] Cycloaddition of Azaheptafulvene with Bicyclo[1.1.0]butanes for the Synthesis of Cycloheptatriene-Fused 2-Azabicyclo[3.1.1]heptanes.

Higher-order cycloadditions are a simple and effective strategy for constructing significant medium-sized architectures. Azaheptafulvenes reacting with readily accessible bicyclo[1.1.

The INO80E at 16p11.2 locus increases risk of schizophrenia in humans and induces schizophrenia-like phenotypes in mice.

Background: Chromosome 16p11.2 is one of the most significant loci in the genome-wide association studies (GWAS) of schizophrenia. Despite several integrative analyses and functional genomics studies having been carried out to identify possible risk genes, their impacts in the pathogenesis of schizophrenia remain to be fully characterized.

Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression.

Deciphering the genetic architecture of depression is pivotal for characterizing the associated pathophysiological processes and development of new therapeutics. Here we conducted a cross-ancestry genome-wide meta-analysis on depression (416,437 cases and 1,308,758 controls) and identified 287 risk loci, of which 49 are new. Variant-level fine mapping prioritized potential causal variants and functional genomic analysis identified variants that regulate the binding of transcription factors.

Human mood disorder risk gene Synaptotagmin-14 contributes to mania-like behaviors in mice.

Bipolar disorder (BD) and major depressive disorder (MDD) are the most prevalent mood disorders and cause considerable burden worldwide. Compelling evidence suggests a pronounced overlap between these two disorders in clinical symptoms, treatment strategies, and genetic etiology. Here we leverage a BD GWAS (1822 cases and 4650 controls) and a MDD GWAS (5303 cases and 5337 controls), followed by independent replications, to investigate their shared genetic basis among Han Chinese.

Copper-Catalyzed Propargylation of Terminal Olefins to Skipped Enynes.

A highly efficient and easy to operate method for synthesizing skipped enynes catalyzed by copper has been reported for the first time. A wide variety of skipped enynes were obtained in acceptable to good yields employing nonactivated terminal olefins as nucleophiles under mild conditions. This protocol features broad substrate scope and high functional group tolerance, therefore enabling late-stage functionalization and a scale-up experiment further to highlight the synthetic utility.

Chiral Phosphoric Acid-Catalyzed Asymmetric Synthesis of Axially Chiral Arylpyrazole.

A chiral phosphoric acid-catalyzed efficient, operationally simple, general method for straightforward syntheses of axially chiral arylpyrazole employing -alkyl of 3-aryl-5-aminopyrazoles reacting with azonaphthalenes was achieved. A wide variety of axially chiral heterobiaryl diamines in generally good yields with excellent enantioselectivities were obtained under mild conditions. In addition, a scaled-up experiment and postmodification of the chiral product further highlighted the synthetic utility.

Asymmetric Synthesis of Optically Active Pyrazolidines or Pyrazoline Derivatives via Ni(II)-Bipyridine-,'-dioxide Complexes.

Easily obtainable and efficient chiral -symmetric bipyridine-,'-dioxide ligands with Ni(OTf) were developed for application in catalyzing [3 + 2] cycloaddition reactions to synthesize optically active fused pyrazolidines or pyrazoline derivatives featuring three contiguous stereogenic centers by employing azomethine imines and α,β-unsaturated 2-acyl imidazoles, affording the corresponding adducts with the opposite configuration compared to previous synthetic products in 80-98% yields with 28-99% ee and >20:1 dr. In addition, subsequent amplification experiments and derivative transformations of the product further demonstrated the efficient catalytic performance of the catalyst Ni(II)-bipyridine-,'-dioxide complexes and the practicality of this synthesis methodology.

Asymmetric Synthesis of Polycyclic Heterocyclic Compounds via Friedel-Crafts Reaction/Cyclization Reaction Catalyzed by Nickel Catalyst.

The first highly enantioselective asymmetric Friedel-Crafts reaction/cyclization reaction of 5-aminopyrazoles with 3-alkenyloxindoles to afford polycyclic heterocyclic compounds bearing an all-carbon quaternary stereocenter catalyzed by a complex of Ni with the -symmetric bipyridine-,'-dioxide ligand has been developed. The relevant products with a wide range of substrates and good functional tolerance were obtained in 89-98% yield with 56-99% ee in the presence of 10 mol % Ni(OTf) and 11 mol % in DCM at 25 °C. Moreover, an experiment on scaling up the process along with the transformations of the cycloadducts further emphasized the practical application of the synthesis.

Cu(II)-Catalyzed Reaction of Ethynyl Methylene Cyclic Carbamates and Amines: Synthesis of Polysubstituted Pyrroles.

A copper-catalyzed efficient, operationally simple, general method for straightforward syntheses of polysubstituted pyrroles employing ethynyl methylene cyclic carbamates as precursors reacting with commercially available amines was first reported. A wide variety of polysubstituted pyrroles were obtained in acceptable to good yields under mild conditions. This protocol features broad substrate scope, high functional group tolerance, and easy operation, therefore enabling late-stage functionalization and rapid synthesis of bioactive compounds, including structurally complex marketed drugs and natural products.

Asymmetric Synthesis of Chiral Cyclopropanes from Vinyl Sulfoxonium Ylides Catalyzed by a Chiral-at-Metal Rh(III) Complex.

A chiral-at-metal Rh(III) complex-mediated [2+1] cyclization of vinyl sulfoxonium ylides with α,β-unsaturated 2,2-acylimidazoles has been demonstrated for the first time. This work provides a practical approach for assembling 1,2,3-trisubstituted chiral cyclopropane with alkyl structural units, which had advantages such as a wide range of substrates, good functional group tolerance, and mild reaction conditions. In addition, further amplification experiments and transformation of cycloaddition products were carried out to highlight the practicality of the method.

Intermolecular Formal [2π + 2σ] Cycloaddition of Enol Silyl Ethers with Bicyclo[1.1.0]butanes Promoted by Lewis Acids.

Silyl enol ethers react with bicyclo[1.1.0]butanes (BCBs) through Yb(OTf)-promoted formal [2π + 2σ] cycloaddition reactions to furnish bicyclo[2.

Genomic landscape and functional characterization of structural variations in schizophrenia and bipolar disorder.

Multiple types of variations have been postulated to confer risk of schizophrenia and bipolar disorder, but majority of present GWAS solely focused on SNPs or small indels, and the impacts of structural variations (SVs) remain less understood. Nevertheless, accumulating evidence suggest that SVs may explain the association signals in certain GWAS hits. Here, we conducted pairwise linkage disequilibrium (LD) analyses of SNPs and SVs in populations from 1000 Genomes Project.

Bipyridine-,'-dioxides Catalysts: Design, Synthesis, and Application in Asymmetric Synthesis of 1-Pyrazolo[3,4-]pyridine Analogues.

A novel type of highly efficient chiral 2-symmetric bipyridine-,'-dioxides ligand application in catalyzing Michael addition/Cyclization of 5-aminopyrazoles with α,β-unsaturated 2-acyl imidazoles has been developed, affording the corresponding adducts in 85-97% yield with up to 99% enantioselectivity under mild conditions with a lower catalyst loading and broad scope. Remarkably, this protocol exhibits advantages in terms of reactivity and enantioselectivity, giving the fact that as low as 2.2 mol % of and 2.

Research on driver's anger recognition method based on multimodal data fusion.

Objectives: This paper aims to address the challenge of low accuracy in single-modal driver anger recognition by introducing a multimodal driver anger recognition model. The primary objective is to develop a multimodal fusion recognition method for identifying driver anger, focusing on electrocardiographic (ECG) signals and driving behavior signals.

Methods: Emotion-inducing experiments were performed employing a driving simulator to capture both ECG signals and driving behavioral signals from drivers experiencing both angry and calm moods.

Asymmetric Synthesis of Tertiary α-Hydroxylation-Cyclopentanones via Synergetic Catalysis of Chiral-at-Metal Rhodium(III) Complexes/Pyrrolidine.

Catalytic and asymmetric domino Michael/aldol reaction of 1,2-dicarbonyl compounds with α,β-unsaturated ketones under the synergetic catalysis of chiral-at-metal rhodium complexes and pyrrolidine to deliver tertiary α-hydroxylation-cyclopentanones (45-89% yields with 81-99% ee and up to >20:1 dr) bearing three contiguous stereogenic centers had been established. Moreover, the scalability and practical utility of this protocol were well demonstrated by employing a gram-scale reaction and some representative transformations.

Catalytic asymmetric conjugate addition of coumarins to unsaturated ketones catalyzed by a chiral-at-metal Rh(III) complex.

The first catalytic asymmetric vinylogous Michael addition of coumarins to unsaturated ketones catalyzed by chiral rhodium catalysts has been established. This strategy allowed the synthesis of a variety of highly enantioenriched compounds containing coumarin skeletons in 41-99% yields and 84-99% ee. The developed reaction enriches the chemistry of catalytic asymmetric vinylogous Michael additions of 3-cyano-4-methylcoumarins.

Safety of entecavir antiviral therapyduring an accidental pregnancy in patients with chronic hepatitis B.

The present study aimed to investigate the effects of accidental pregnancy CHB patients' reproductive age on their offspring during entecavir (ETV) antiviral therapy. A total of 112 couples were retrospectively enrolled, and they were divided into an observational and control group. A total of 53 couples who had accidental pregnancies while receiving long-term ETV antiviral medication were recruited for the observational group.

Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice.

Background: Genome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs on VRK2 as well as their roles in the illness are yet to be elucidated.

Methods: Based on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulating VRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice with Vrk2 repression.

Results: We identified a SNP rs2678907 located in the 5' upstream of VRK2 gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues.

Expression and secretion of glycosylated barley oxalate oxidase in Pichia pastoris.

Oxalate oxidase is an enzyme that degrades oxalate and is used in commercial urinary assays to measure oxalate levels. The objective of this study was to establish an enhanced expression system for secretion and purification of oxalate oxidase using Pichia pastoris. A codon optimized synthetic oxalate oxidase gene derived from Hordeum vulgare (barley) was generated and cloned into the pPICZα expression vector downstream of the N-terminal alpha factor secretion signal peptide sequence and used for expression in P.

Non-invasive methods to evaluate liver fibrosis in patients with non-alcoholic fatty liver disease.

Non-alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease that is strongly related to insulin resistance and metabolic syndrome, and it has become the most common liver disorder in developed countries. NAFLD embraces the full pathological process of three conditions: steatosis, non-alcoholic steatohepatitis, and finally, cirrhosis. As NAFLD progresses, symptoms will become increasingly severe as fibrosis develops.