Common variants in Neuraminidases genes contribute to predisposition to and progression of chronic heart failure.

Introduction The role of neuraminidases in cardiovascular disease has recently gained increasing attention. However, the association between neuraminidase gene polymorphisms and heart failure (HF) has not yet been investigated. Methods and Results Genotyping of nine single nucleotide polymorphisms (SNPs) in the NEU2/NEU3/NEU4 genes was performed in 610 HF patients and 600 healthy controls from the Southwest Han Chinese population using TaqMan SNP Genotyping Assay. Individuals carrying the A allele of rs11545301 had decreased risk of HF (additive model: OR=0.704, 95% CI=0.511-0.97; P = 0.032). While the C allele of rs2293763 increased the risk of HF in recessive model (OR=1.486, 95% CI=1.095-2.012; P = 0.011). Rs2233384, rs2233394 and rs2293763 were significantly associated with the mortality risk of HF in dominant model, both with and without adjustment for conventional risk factors (HR= 0.686, 95% CI= 0.52-0.906, P = 0.008 for rs2233384; HR= 1.357, 95% CI= 1.035-1.78, P = 0.027 for rs2233384 and HR= 0.76, 95% CI= 0.592-0.975; P = 0.031 for rs2293763). Conclusion Our findings demonstrated the association between a series of variants in NEU2/NEU4 genes and the risk or prognosis of HF in Han Chinese Population. These data suggested an important role of NEU2 and NEU4 in the pathogenesis of HF.

Highly selective AlCl3 initiated intramolecular α-alkylation of α,ß-unsaturated lactams and lactones.

An unprecedented example of AlCl3 initiated intramolecular α-alkylation of α,ß-unsaturated lactams and lactones is reported. A variety of substrates containing an intramolecular diene yield exclusively regioselective six-membered ring products. This reaction protocol generates a new stereo centre which may be of high interest for the functionalization of bioactive coumarin and quinolinone derivatives.

Cu(II)-Catalyzed 6π-Photocyclization of Dienynes.

The first 6π-photocyclization of dienynes was developed, which provides a new and effective protocol for the synthesis of the phenyl ring in excellent yields with nice functional group tolerance. In this transformation, the Cu(OTf)2 catalyst plays a key role in the conversion of alkyne moiety into an alkene-type moiety, which means that the dienyne reactant is converted into a triene-type substrate. Thus, this reaction proceeds via a Cu(II)-catalyzed 6π-photocyclization of triene-type derivatives.

An eleven autophagy-related genes-based prognostic signature for endometrial carcinoma.

BACKGROUND: Endometrial cancer (EC) is a common malignant tumor in women with increasing mortality. The prognosis of EC is highly heterogeneous which needs more effective biomarkers for clinical decision. Here, we reported the effect of autophagy-related genes (ARGs) on the prognosis of EC. METHODS: The expression data of EC tissues and adjacent non-tumor samples were available from the TCGA dataset and 232 autophagy-related genes were from The Human Autophagy Database. A prognostic ARGs risk model was further constructed by using LASSO-Cox regression, and its prognostic and predictive value were evaluated by nomogram. Further functional analysis was conducted to reveal a significant signaling pathway. RESULTS: A total of 45 differentially expressed ARGs were obtained, including 18 upregulated and 27 downregulated genes. Eleven ARGs (BID, CAPN2, CDKN2A, DLC1, GRID2, IFNG, MYC, NRG3, P4HB, PTK6, and TP73) were finally selected to build ARGs risk. This signature could well distinguish between the high- and low-risk patients (survival analysis: P = 1.18E-10; AUC: 0.733 at 1 year, 0.795 at 3 years, and 0.823 at 5 years). Furthermore, a nomogram was plotting to predict the possibility of overall survival and suggested good value for clinical utility. CONCLUSION: We established an eleven-ARG signature, which was probably effective in the prognostic prediction of patients with EC.

Visible light-induced one-pot synthesis of CF3/CF2-substituted cyclobutene derivatives.

An efficient one-pot approach for the controllable synthesis of trifluoromethyl/gem-difluoromethylene substituted cyclobutene derivatives has been developed. The mechanism may involve visible light-induced [2+2]-cycloaddition of quinolinones with 1-bromo-1-trifluoromethylethene, followed by base-promoted dehydrobromination, [1,3]-H shift and further dehydrofluorination. A variety of CF3/CF2-substituted cyclobutenes that are currently difficult to obtain are afforded in good yields in this protocol, which may find its way into future fluorinated cyclobutene preparation.

Visible Light-Induced Pericyclic Cascade Reaction for the Synthesis of Quinolinone Derivatives with an Oxabicyclo[4.2.0]octene Skeleton.

A photoinduced pericyclic cascade reaction has been developed to afford oxabicyclo[4.2.0]octenes. Mechanistic studies show that this reaction undergoes [2 + 2]-photocycloaddition, base-promoted elimination, retro-4π-electrocyclization, [1,5]-H shift, and 4π-electrocyclization procedures. This reaction features wide substrate scope, good functional group tolerance, and excellent diastereoselectivity.

Visible-Light-Induced Dehydrohalogenative Coupling for Intramolecular α-Alkenylation: A Way to Build Seven- and Eight-Membered Rings.

A visible-light-induced intramolecular α-alkenylation has been developed via metal-free dehydrohalogenative C(sp2)-C(sp2) coupling reaction to afford seven- and eight-membered rings. Extensive mechanistic studies prove that this reaction proceeds through a [2 + 2]-photocycloaddition, elimination, and retro-[2 + 2]-photocycloaddition process, with cyclobutane and cyclobutene being involved as key intermediates. This transformation is broadly applicable and highly stereoselective, yielding exclusively cyclic (1Z,3Z)-1,3-diene via photochemically allowed disrotation. This protocol excavates new applications of [2 + 2]-photocycloadditions, which may find their way in future olefin-olefin coupling reactions and medium-sized ring synthesis.

Immediate and short-term effects of transcatheter device closure of large atrial septal defect in senior people.

OBJECTIVES: We sought to evaluate the safety and efficacy in improving cardiac function and functional capacity with device closure of large atrial septal defects (ASD) in senior adults. BACKGROUND: Atrial septal defect accounts for about 10% of all congenital heart disease. It still remains unclear whether large ASD closure in senior people should be performed or not. Hence we aim to prospectively assess the safety and clinical status of senior patients after transcatheter closure in large ASD. PATIENTS AND INTERVENTIONS: This was a prospective study of all patients aged over 50 years who underwent device closure of a secundum large ASD between January 2013 and January 2018. Investigations including brain natriuretic peptide level, electrocardiography, chest X-ray, transthoracic echocardiogram, transesophageal echocardiogram, and 6-minute walk test were performed before and at 2 days and 4 weeks and 6 months after the procedure. RESULTS: Twenty patients (median age 68 years, 10 women) had transcatheter device closure of large ASD successfully. Median ASD size was 32 mm (range 30-39 mm). Median pulmonary artery pressure was 58 mm Hg (range 47-67 mm Hg). At 6 months, there was a significant change in right atrium size (P < .001) and right ventricle size (P < .01) and left ventricle size (P < .001) and also pulmonary artery pressure (P < .0001), New York Heart Association functional class improved (P = .03) in 19 patients and also significant improvement in 6-minute walk test distance (P < .001). There were no major complications. CONCLUSIONS: Our data showed that large ASD closure at senior people results in satisfactory cardiac remodeling and cardiac function improvement.

Resequencing of 429 chickpea accessions from 45 countries provides insights into genome diversity, domestication and agronomic traits.

We report a map of 4.97 million single-nucleotide polymorphisms of the chickpea from whole-genome resequencing of 429 lines sampled from 45 countries. We identified 122 candidate regions with 204 genes under selection during chickpea breeding. Our data suggest the Eastern Mediterranean as the primary center of origin and migration route of chickpea from the Mediterranean/Fertile Crescent to Central Asia, and probably in parallel from Central Asia to East Africa (Ethiopia) and South Asia (India). Genome-wide association studies identified 262 markers and several candidate genes for 13 traits. Our study establishes a foundation for large-scale characterization of germplasm and population genomics, and a resource for trait dissection, accelerating genetic gains in future chickpea breeding.

A Newly Designed Mobile-Based Computerized Cognitive Addiction Therapy App for the Improvement of Cognition Impairments and Risk Decision Making in Methamphetamine Use Disorder: Randomized Controlled Trial.

BACKGROUND: Cognitive rehabilitation therapy has been found to improve cognitive deficits and impulse control problems in methamphetamine use disorder (MUD). However, there is limited research regarding this therapy's feasibility when using mobile-based health technologies in supporting recovery from MUD in China. OBJECTIVE: The main aim of this study was to test whether 4 weeks of a newly designed computerized cognitive addiction therapy (CCAT) app can improve cognitive impairments, eliminate drug-related attention bias, and attenuate risk decision-making behaviors in participants with MUD. METHODS: Forty MUD participants were assigned randomly to either the CCAT group (n=20), who received 4 weeks of CCAT plus regular detoxification treatment as usual, or the control group (n=20), who only received the regular detoxification treatment as usual, in drug rehabilitation centers in Shanghai. The CCAT was designed by combine methamphetamine use-related picture stimuli with cognitive training with the aim of improving cognitive function and eliminating drug-related attention bias. The CogState Battery, Delay Discounting Task (DDT), Iowa Gambling Task (IGT), and Balloon Analog Risk Task (BART) were administered face-to-face to all participants before and after CCAT interventions. RESULTS: Forty male patients were recruited. The mean age was 32.70 (SD 5.27) years in the CCAT group and mean 35.05 (SD 8.02) years in the control group. Compared to the control group, CCAT improved working memory in the CCAT group (P=.01). Group×time interactions were observed among DDT, IGT, and BART tasks, with rates of discounting delayed rewards, IGT, and BART scores (P<.001) being reduced among those who received CCAT, whereas no changes were found in the control group. CONCLUSIONS: The newly designed CCAT can help to improve cognitive impairment and impulsive control in MUD. Further study is needed to understand the underlying brain mechanisms of the cognitive therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03318081; https://clinicaltrials.gov/ct2/show/NCT03318081 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT03318081).

Construction of the third-generation Zea mays haplotype map.

Background: Characterization of genetic variations in maize has been challenging, mainly due to deterioration of collinearity between individual genomes in the species. An international consortium of maize research groups combined resources to develop the maize haplotype version 3 (HapMap 3), built from whole-genome sequencing data from 1218 maize lines, covering predomestication and domesticated Zea mays varieties across the world. Results: A new computational pipeline was set up to process more than 12 trillion bp of sequencing data, and a set of population genetics filters was applied to identify more than 83 million variant sites. Conclusions: We identified polymorphisms in regions where collinearity is largely preserved in the maize species. However, the fact that the B73 genome used as the reference only represents a fraction of all haplotypes is still an important limiting factor.

Merging photoredox catalysis with Lewis acid catalysis: activation of carbon-carbon triple bonds.

Here, we demonstrate that merging photoredox catalysis with Lewis acid catalysis provides a fundamentally new activation mode of C-C triple bonds, to achieve the bond-forming reaction of alkynes with weak nucleophiles. Using a synergistic merger of Eosin Y and Cu(OTf)2, a highly efficient cyclization reaction of arene-ynes was developed.

Supramolecular metal-organic frameworks that display high homogeneous and heterogeneous photocatalytic activity for H2 production.

Self-assembly has a unique presence when it comes to creating complicated, ordered supramolecular architectures from simple components under mild conditions. Here, we describe a self-assembly strategy for the generation of the first homogeneous supramolecular metal-organic framework (SMOF-1) in water at room temperature from a hexaarmed [Ru(bpy)3](2+)-based precursor and cucurbit[8]uril (CB[8]). The solution-phase periodicity of this cubic transition metal-cored supramolecular organic framework (MSOF) is confirmed by small-angle X-ray scattering and diffraction experiments, which, as supported by TEM imaging, is commensurate with the periodicity in the solid state. We further demonstrate that SMOF-1 adsorbs anionic Wells-Dawson-type polyoxometalates (WD-POMs) in a one-cage-one-guest manner to give WD-POM@SMOF-1 hybrid assemblies. Upon visible-light (500 nm) irradiation, such hybrids enable fast multi-electron injection from photosensitive [Ru(bpy)3](2+) units to redox-active WD-POM units, leading to efficient hydrogen production in aqueous media and in organic media. The demonstrated strategy opens the door for the development of new classes of liquid-phase and solid-phase ordered porous materials.

Recent breeding programs enhanced genetic diversity in both desi and kabuli varieties of chickpea (Cicer arietinum L.).

In order to understand the impact of breeding on genetic diversity and gain insights into temporal trends in diversity in chickpea, a set of 100 chickpea varieties released in 14 countries between 1948 and 2012 were re-sequenced. For analysis, the re-sequencing data for 29 varieties available from an earlier study was also included. Copy number variations and presence absence variations identified in the present study have potential to drive phenotypic variations for trait improvement. Re-sequencing of a large number of varieties has provided opportunities to inspect the genetic and genomic changes reflecting the history of breeding, which we consider as breeding signatures and the selected loci may provide targets for crop improvement. Our study also reports enhanced diversity in both desi and kabuli varieties as a result of recent chickpea breeding efforts. The current study will aid the explicit efforts to breed for local adaptation in the context of anticipated climate changes.

Effect of autonomic nervous system on the transmural dispersion of ventricular repolarization in intact canine.

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (MAPs) of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall in 12 open-chest dogs. MAPD90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD90 of Epi, Mid and Endo before autonomic nervous stimulation were 278 +/- 11 ms, 316 +/- 16 ms and 270 +/- 12 ms respectively, the MAPD90 of Mid was significantly longer than that of Epi or Endo (P<0.01). MAPD90 of Epi, Mid and Endo were shortened by 19 +/- 4 ms, 45 +/- 6 ms, 18 +/- 3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44 +/- 4 ms to 15 +/- 3 ms (P<0.01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41%) during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.

Experimental study of the effect of autonomic nervous system on the transmural dispersion of ventricular repolarization under acute myocardial ischemia in vivo.

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), mid-myocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs. MAPD90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial ischemia, TDR was increased from 55 +/- 8 ms to 86 +/- 15 ms during sympathetic stimulation (P < 0.01). The TDR (53 +/- 9 ms) during parasympathetic stimulation was not significantly different from that of the control (55 +/- 8 ms) (P > 0.05). The EAD was elicited in the Mid of 2 dogs (16%) 10 min after acute myocardial ischemia, but the EAD were elicited in the Mid of 7 dogs (58%) during sympathetic stimulation (P < 0.01). It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolarization and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which provide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.