Cobalt-catalyzed amination of aziridines and azetidines toward 1,2- and 1,3-diamines.

Diamines play important roles in synthetic organic chemistry and thus facilitate life and materials sciences. Herein we report a cobalt-catalyzed ring opening, nucleophilic amination of aziridines and azetidines with N-fluorosulfonamides toward a wide range of 1,2- and 1,3-diamine derivatives in moderate to good yields under mild conditions.

Nickel-Catalyzed Selective C(sp2 )-F Bond Alkylation of Industrially Relevant Hydrofluoroolefin HFO-1234yf.

The selective transition-metal catalyzed C-F bond functionalization of inexpensive industrial fluorochemicals represents one of the most attractive approaches to valuable fluorinated compounds. However, the selective C(sp2 )-F bond carbofunctionalization of refrigerant hydrofluoroolefins (HFOs) remains challenging. Here, we report a nickel-catalyzed selective C(sp2 )-F bond alkylation of HFO-1234yf with alkylzinc reagents. The resulting 2-trifluoromethylalkenes can serve as a versatile synthon for diversified transformations, including the anti-Markovnikov type hydroalkylation and the synthesis of bioactive molecule analogues. Mechanistic studies reveal that lithium salt is essential to promote the oxidative addition of Ni0 (Ln ) to the C-F bond; the less electron-rich N-based ligands, such as bipyridine and pyridine-oxazoline, feature comparable or even higher oxidative addition rates than the electron-rich phosphine ligands; the strong σ-donating phosphine ligands, such as PMe3 , are detrimental to transmetallation, but the less electron-rich and bulky N-based ligands, such as pyridine-oxazoline, facilitate transmetallation and reductive elimination to form the final product.

Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm.

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

Effects of adaptive left bundle branch-optimized cardiac resynchronization therapy: a single centre experience.

BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is associated with improved clinical outcomes. Left bundle branch area pacing (LBBAP) has shown encouraging results as an alternative option for aCRT. A technique that can be accomplished effectively using LBBAP combined with coronary venous pacing (LOT-aCRT). We aimed to assess the feasibility and outcomes of LOT-aCRT. METHODS: LOT-aCRT, capable of providing two pacing modes, LBBAP alone or LBBAP combined with LV pacing, was attempted in patients with CRT indications. Patients were divided into two groups: those with LBBAP and LV pacing (LOT-aCRT) and those with conventional biventricular pacing (BVP-aCRT). RESULTS: A total of 21 patients were enrolled in the study (10 in the LOT-aCRT group, 11 in the BVP-aCRT group). In the LOT-aCRT group, the QRS duration (QRSd) via BVP was narrowed from 158.0 ± 13.0 ms at baseline to 132.0 ± 4.5 ms (P = 0.019) during the procedure, and further narrowed to 123.0 ± 5.7 ms (P < 0.01) via LBBAP. After the procedure, when LOT-aCRT implanted and worked, QRSd was further changed to 121.0 ± 3.8 ms, but the change was not significant (P > 0.05). In the BVP-aCRT group, BVP resulted in a significant reduction in the QRSd from 176.7 ± 19.7 ms at baseline to 133.3 ± 8.2 ms (P = 0.011). However, compared with LOT-aCRT, BVP has no advantage in reducing QRSd and the difference was statistically significant (P < 0.01). During 9 months of follow-up, patients in both groups showed improvements in the LVEF and NT-proBNP levels (all P < 0.01). However, compared with BVP-aCRT, LOT-aCRT showed more significant changes in these parameters (P < 0.01). CONCLUSIONS: The study demonstrates that LOT-aCRT is clinically feasible in patients with systolic heart failure and LBBB. LOT-aCRT was associated with significant narrowing of the QRSd and improvement in LV function.

[Application of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain]. / è¶ å£°å¼•å¯¼å† é•œä¸‹é€†è¡Œé˜‘å°¾ç‚Žæ²»ç–—æœ¯åœ¨é˜‘å°¾ç›¸å ³æ ¢æ€§è ¹ç—›æ‚£å„¿ä¸­çš„åº”ç”¨ä»·å€¼.

OBJECTIVES: To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain. METHODS: A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate. RESULTS: Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×109/L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%). CONCLUSIONS: Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.

A de novo variant of POLR3B causes demyelinating Charcot-Marie-Tooth disease in a Chinese patient: a case report.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants. CASE PRESENTATION: A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A). CONCLUSIONS: In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.

Exonic rearrangements in DMD in Chinese Han individuals affected with Duchenne and Becker muscular dystrophies.

Exonic deletions and duplications within DMD are the main pathogenic variants in Duchenne and Becker muscular dystrophies (DMD/BMD). However, few studies have profiled the flanking sequences of breakpoints and the potential mechanism underlying the breakpoints in different fragile regions of DMD. In this study, 896 Chinese male probands afflicted with DMD/BMD were selected from unrelated families and analyzed using multiplex ligation-dependent probe amplification of the DMD gene, in which we identified exon deletions in 784 subjects and duplications in 112 subjects. Deletions occurred most frequently in the genomic region encompassing exons 45-55, accounting for 73% of all deletion patterns. Furthermore, to unravel the potential mechanism that induced breaks, DMD gene capture and sequencing were performed to identify the breakpoints in 37 subjects with deletions encompassing exons 45-55 of DMD; we found that DMD instability did not arise from a single cause; instead, long-sequence motifs, nonconsensus microhomologies, low-copy repeats, and microindels were embedded around the breakpoints, which may predispose DMD to instability. In summary, this study highlights the heterogeneous characteristics of the flanking sequences around the breakpoints and helps us to understand the mechanism underlying DMD gene instability.

Berberine Attenuates Cholesterol Accumulation in Macrophage Foam Cells by Suppressing AP-1 Activity and Activation of the Nrf2/HO-1 Pathway.

Atherosclerosis is a chronic inflammation condition resulting from the interaction between lipoproteins, monocyte-derived macrophages, T lymphocytes, and other cellular elements in the arterial wall. Macrophage-derived foam cells play a key role in both early and advanced stage of atherosclerosis. Previous studies have shown that berberine could inhibit foam cell formation and prevent experimental atherosclerosis. However, its underlying molecular mechanisms have not been fully clarified. In this study, we explored the cholesterol-lowering effects of berberine in macrophage-derived foam cells and investigated its possible mechanisms in prevention and treatment of atherosclerosis. Here, we demonstrated that berberine could inhibit atherosclerosis in apolipoprotein E-deficient mice and induce cholesterol reduction as well as decrease the content of macrophages. Berberine can regulate oxLDL uptake and cholesterol efflux, thus suppresses foam cell formation. Mechanisms study showed that berberine can suppress scavenger receptor expression via inhibiting the activity of AP-1 and upregulate ATP-binding cassette transporter via activating Nrf2/HO-1 signaling in human macrophage. In summary, berberine significantly inhibits atherosclerotic disease development by regulating lipid homeostasis and suppressing macrophage foam cell formation.

Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome.

BACKGROUND: Nance-Horan syndrome (NHS) is an X-linked inheritance disorder characterized by bilateral congenital cataracts, and facial and dental dysmorphism. This disorder is caused by mutations in the NHS gene. However, NHS may be difficult to detect in individuals with subtle facial dysmorphism and dental abnormalities in whom congenital cataracts are the primary clinical manifestations. METHODS: In this study, we present a three-generation family with NHS. Whole exome sequencing was performed to determine the potential pathogenic variant in the proband. Further validation was explored with Sanger sequencing in 9 of the available individuals of the family and additional 200 controls. RESULTS: A novel truncation mutation in gene NHS (c.C4449G, p.Tyr1483Ter) was found in the proband, who presented with a long-narrow face, prominent nose and large anteverted pinnae ear, screw-driver like incisors, mild mulberry like molars, one missing maxillary second molar and malocclusion. We found this mutation was detected in 2 male patients and 4 female carriers in the family. However, the mutation was never detected in the control subjects. CONCLUSIONS: In conclusion, we identified a novel truncation mutation in the NHS gene, which might associate with NHS. Our review on the NHS studies illustrated that NHS has significantly clinical heterogeneity. And NHS mutations in the NHS-affected individuals typically result in premature truncation of the protein. And the new mutation revealed in this study would highlight the understanding of the causative mutations of NHS.

Risk factor analysis of device-related infections: value of re-sampling method on the real-world imbalanced dataset.

BACKGROUND: The incidence of cardiac implantable electronic device infection (CIEDI) is low and usually belongs to the typical imbalanced dataset. We sought to describe our experience on the management of the imbalanced CIEDI dataset. METHODS: Database from two centers of patients undergoing device implantation from 2001 to 2016 were reviewed retrospectively. Re-sampling technique was used to improve the classifier accuracy. RESULTS: CIEDI was identified in 28 out of 4959 procedures (0.56%); a high imbalance existed in the sizes of the patient profiles. In univariate analyses, replacement procedure and male were significantly associated with an increase in CIEDI: (53.6% vs. 23.4, 0.8% vs. 0.3%, P < 0.01). Multivariate logistic regression analysis showed that gender (odds ratio, OR = 3.503), age (OR = 1.032), replacement procedure (OR = 3.503), and use of antibiotics (OR = 0.250) remained as independent predictors of CIEDI (all P < 0.05) after adjustment for diabetes, post-operation fever, and device style, device company. There were 616 under-sampled cases and 123 over-sampled cases in the analyzed cohort after re-sampling. The re-sampling and bootstrap results were robust and largely like the analysis results prior re-sampling method, while use of antibiotics lost the predicting capacity for CIEDI after re-sampling technique (P > 0.05). CONCLUSION: The application of re-sampling techniques can generate useful synthetic samples for the classification of imbalanced data and improve the accuracy of predicting efficacy of CIEDI. The peri-operative assessment should be intensified in male and aged patients as well as patients receiving replacement procedures for the risk of CIEDI.

Associated and predictive factors of quality of life in patients with temporal lobe epilepsy.

OBJECTIVE: Identifying the factors that are correlated with and predictive of reduced quality of life (QOL) is essential to optimize the treatment of epilepsy and the management of comorbidities. METHODS: We analyzed the independent associations between the Quality of Life in Epilepsy-31 (QOLIE-31) inventory and the demographic, clinical, psychiatric, and cognitive variables of 47 consecutive patients with temporal lobe epilepsy (TLE). Predictors of the correlated variables were analyzed by multiple linear regression analysis. RESULTS: The QOLIE-31 total score was positively correlated with occupational status and Mini-Mental State Examination (MMSE) scores (r = 0.290 and 0.295, respectively; P < 0.05) and negatively correlated with the duration of seizures, adverse effects of antiepileptic drugs (AEDs), and the Pittsburgh Sleep Quality Inventory (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) scores (r = -0.357, 0.321, 0.328, -0.672, and -0.565, respectively; P < 0.05; P < 0.01 for the SAS and SDS). In the final multivariate regression model, anxiety, long durations of seizures, adverse effects of AEDs, and depression explained approximately 60.6% (adjusted R2 = 0.606, R coefficient = 0.800) of the QOLIE-31 overall score variance. CONCLUSION: Anxiety, long durations of seizures, adverse effects of AEDs, and depression were significant predictors of QOL, and these variables had relatively high prediction capacities for the overall QOLIE-31 in the regression model. Comorbid anxiety is the most powerful negative determinant of the QOLIE-31.

Microalgae cultivation and nutrients removal from sewage sludge after ozonizing in algal-bacteria system.

The feasibility of growing algae in concentrated wastewater generated from sludge ozonation for simultaneous nutrients removal and biomass production was studied. The effects of bacteria addition into microalgae on nutrients removal, biomass yield and settleability, the growth rate of algae and concentrations of extracellular polymeric substances (EPS) and soluble microbial products (SMP) were investigated. The results showed that the growth rate of algae in algal-bacteria system (0.2182) was improved than in algae-only system (0.1852), while both of them are comparable with others reported previously. And the addition of bacteria enhanced COD, NH4+-N, TN and TP removal rate by 23.9 ±â€¯3.3%, 27.7 ±â€¯3.6%, 16.6 ±â€¯1.8% and 14.9 ±â€¯2.2%, respectively. And 32.8 ±â€¯0.7% of the TN and 50.3 ±â€¯1.8% of the TP were recycled from ozonated sludge-supernatant (OSS) being absorbed into algal-bacterial biomass. The algal-bacteria system also demonstrated advantages on biomass settleability and heavy metals removal. Finally, the mechanism involving matter exchange and algal-bacteria system on OSS treatment in this study were discussed through evaluation of nutrients, SMP and EPS contents, nitrogen and phosphorus balance.

Visible-Light-Promoted Tandem Difluoroalkylation-Amidation: Access to Difluorooxindoles from Free Anilines.

An efficient and synthetically convenient method for the synthesis of 3,3-difluoro-2-oxindole through a visible-light-induced photoredox difluoromethylation-amidation is described. The process can generate a broad range of difluorooxindoles using bromodifluoroacetate and broadly available free anilines. The wide range of substrate tolerance and mild reaction conditions make this transformation a highly valuable method in applications for drug discovery and development.

[Effect of eicosapentaenoic acid on mRNA expression of tight junction protein ZO-1 in intestinal epithelial cells after Escherichia coli LF82 infection].

OBJECTIVE: To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection. METHODS: The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 µmol/L EPA) and EPA (0, 25, 50, 100, and 200 µmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant. RESULTS: After EPA treatment (25 and 50 µmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P<0.05). The EPA treatment (100 and 200 µmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P<0.05). The EPA treatment (100 and 200 µmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P<0.05). The 6- and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 µmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). The Caco-2 cells treated with E.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated Caco-2 cells (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 µmol/L EPA for 6 or 12 hours showed a reduction in the secretion of TNF-α with the increasing concentration of EPA and had significantly lower secretion than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). CONCLUSIONS: EPA can effectively prevent the destruction of tight junction of intestinal epithelial cells induced by E.coli LF82 infection and inhibit the secretion of inflammatory factors. Therefore, it has a certain protective effect on intestinal mucosal barrier.

Dual-specificity phosphatase 14 protects the heart from aortic banding-induced cardiac hypertrophy and dysfunction through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway.

Dual-specificity phosphatase 14 (Dusp14), an important negative modulator of mitogen-activated protein kinase (MAPK) signaling pathways, has been implicated in inflammatory immune response, cancers, cell differentiation and proliferation. The role of Dusp14 in chronic pressure overload-induced cardiac hypertrophy has not been explored. Here we have shown that Dusp14-/- knockout mice and cardiac-specific Dusp14 transgenic mice were generated and subjected to aortic banding (AB) for 4 weeks. Our results demonstrated that genetic loss of Dusp14 significantly aggravated cardiac hypertrophy, fibrosis, ventricular dilation and dysfunction, whereas transgenic cardiac-specific Dusp14 overexpression significantly attenuated AB-induced cardiac dysfunction and remodeling. In vitro, adenoviral overexpression of constitutive Dusp14 blocked angiotensin II-induced hypertrophic growth of cardiomyocytes, while Dusp14 knockdown led to opposite effects. Mechanistically, excessive phosphorylation of TAK1, P38MAPK and JNK1/2 was evidenced in Dusp14-/- knockout mice post-AB and inactivation of TAK1-P38MAPK and -JNK1/2 signaling using TAK1 inhibitor 5Z-7-ox shares similar antihypertrophic effect as Dusp14 overexpression. Moreover, we show that Dusp14 directly interacted with TAK1. Results from present experiments indicate that Dusp14 protects the heart from AB-induced cardiac hypertrophy and dysfunction possibly through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway. Future studies are warranted to test the feasibility of overexpressing Dusp14 as a therapeutic strategy to attenuate cardiac hypertrophy and failure.

TRIM28 as an independent prognostic marker plays critical roles in glioma progression.

Tripartite motif (TRIM) proteins are involved in tumorigenesis. Here, we examined the expression, biological function, and clinical significance of tripartite motif containing 28 (TRIM28) in glioma, a locally aggressive brain tumor. First, TRIM28 expression was significantly higher in glioma (n = 138) than in non-glioma controls (n = 6). TRIM28 expression was positively correlated with tumor malignancy, and associated with poor overall survival (OS) and progression-free survival (PFS). Notably, TRIM28 expression was negatively correlated with p21 expression in patients with glioblastoma multiforme (GBM). A multivariate analysis that included relevant measures indicated that high TRIM28 expression is an independent prognostic factor for poor OS and PFS in GBM patients. In experiments with cultured glioma cells, down-regulating TRIM28 with shRNA increased p21 expression, and induced cell cycle arrest at the G1 phase. In a xenograft model, down-regulating TRIM28 suppressed tumor growth. These results indicate that over-expression of TRIM28 is associated with poor outcome in glioma patients.

Subgroup characteristics of insular low-grade glioma based on clinical and molecular analysis of 42 cases.

Although the classification of insular glioma has been established based on the anatomical location in order to facilitate personalized surgical resection, the diagnosis based on anatomical and functional characteristics becomes more complex when insular tumors extend into either the frontobasal brain region and/or the temporal lobe, as part of the limbic system. Moreover, prognosis of insular tumor resection is still controversial. Further analysis of subgroup characteristics of insular grade II gliomas based on clinical and molecular analysis is required to reliably determine patients' survival rates. In this retrospective study 20 purely insular grade II gliomas patients and 22 paralimbic grade II gliomas that involved frontal and/or temporal lobes were compared with regard to epidemiological and clinical characteristics. The molecular profiles including Isocitrate dehydrogenase 1 (IDH1), telomerase reverse transcriptase (TERT) promoter, and P53 mutations, 1p19q co-deletion were analyzed, and microRNA profiles were assessed by microarray and bioinformatics analysis. Purely insular grade II gliomas displayed a high frequency of IDH1 mutations with favorable outcome. IDH1 mutated paralimbic glioma shared many parameters with the purely insular glioma in respect to growth patterns, survival, and microRNA profile, but differed significantly from the IDH1 wild type paralimbic gliomas. Our findings suggest that IDH1 mutations can define subpopulations of insular gliomas with distinct disease entities regardless of tumor extension patterns. These findings could be useful to develop a customized treatment strategy for insular glioma patients.

Semaphorin 3a transfection into the left stellate ganglion reduces susceptibility to ventricular arrhythmias after myocardial infarction in rats.

AIMS: Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling. METHODS AND RESULTS: Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups. CONCLUSION: Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis.

Tandem Difluoroalkylation-Arylation of Enamides Catalyzed by Nickel.

A nickel-catalyzed three-component reaction for the synthesis of difluoroalkylated compounds through tandem difluoroalkylation-arylation of enamides has been developed. The reaction tolerates a variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The significant advantages of this protocol are the low-cost nickel catalyst, synthetic convenience, excellent functional-group compatibility and high reaction efficiency.