Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

Photo-catalyzed acetoxysulfoximination of styrene with sulfoximidoyl thianthrenium salt.

We report the design and synthesis of a redox-active thianthrenium-containing sulfoximination reagent. Photo-catalyzed acetoxysulfoximination of styrene with various functional groups is described. Preliminary mechanistic studies indicated that the sulfoximination reagent (2aa) received a single electron transfer (SET) from the photo-excited Ir(ppy)3 catalyst to produce a sulfoximidoyl radical as a key intermediate in this transformation.

RNF38 inhibits osteosarcoma cell proliferation by binding to CRY1.

The PI3K/AKT pathway plays an important role in the development of osteosarcoma. RNF38 interferes with activation of the AKT pathway. Cryptochrome1 (CRY1) inhibits osteosarcoma proliferation through the AKT pathway. We aimed to clarify whether RNF38 affects the proliferation of osteosarcoma cells by regulating the PI3K/AKT pathway through its interaction with CRY1. The mRNA levels of RNF38 were determined using qRT-PCR. Protein levels of RNF38, p-p70S6, p70S6, +p-AKT, AKT, p-mTOR, mTOR, and CRY1 were detected by western blotting. The proliferation of osteosarcoma cells was detected using CCK-8 and colony formation assays. The interaction between CRY1 and RNF38 was detected by co-immunoprecipitation and GST pull-down assays. RNF38 expression was higher in Saos-2 and U20S cells than in hFOB cells. Overexpression of RNF38 promoted the proliferation of osteosarcoma cells, the number of colonies, and p-AKT and p-mTOR levels, suggesting that overexpression of RNF38 activated the PI3K/AKT pathway. In addition, RNF38 directly binds to the N-terminal of CRY1. The simultaneous knockdown of RNF38 and CRY1 restored the level of p-AKT, which was reduced by RNF38 knockdown alone. RNF38 affects the proliferation of osteosarcoma cells by regulating the PI3K/AKT pathway through its interaction with CRY1.

Photoinduced Acetylation of Anilines under Aqueous and Catalyst-Free Conditions.

A green and efficient visible-light induced functionalization of anilines under mild conditions has been reported. Utilizing nontoxic, cost-effective, and water-soluble diacetyl as photosensitizer and acetylating reagent, and water as the solvent, a variety of anilines were converted into the corresponding aryl ketones, iodides, and bromides. With advantages of environmentally friendly conditions, simple operation, broad substrate scope, and functional group tolerance, this reaction represents a valuable method in organic synthesis.

Faradaic Counter for Liposomes Loaded with Potassium, Sodium Ions, or Protonated Dopamine.

Collisional electrochemistry between single particles and a biomimetic polarized micro-liquid/liquid interface has emerged as a novel and powerful analytical method for measurements of single particles. Using this platform, rapid detection of liposomes at the single particle level is reported herein. Individual potassium, sodium, or protonated dopamine-encapsulated (pristine or protein-decorated) liposomes collide and fuse with the polarized micro-liquid/liquid interface accompanying the release of ions, which are recorded as spike-like current transients of stochastic nature. The sizing and concentration of the liposomes can be readily estimated by quantifying the amount of encapsulated ions in individual liposomes via integrating each current spike versus time and the spike frequency, respectively. We call this type of nanosensing technology "Faradaic counter". The estimated liposome size distribution by this method is in line with the dynamic light scattering (DLS) measurements, implying that the quantized current spikes are indeed caused by the collisions of individual liposomes. The reported electrochemical sensing technology may become a viable alternative to DLS and other commercial nanoparticle analysis systems, for example, nanoparticle tracking analysis.

Photoinduced Deaminative Coupling of Alkylpyridium Salts with Terminal Arylalkynes.

A novel and simple Z-alkene synthesis by the photocatalyzed coupling reactions of alkylpyridium salts, which were prepared from primary amines, with terminal aryl alkynes at room temperature is reported here. A wide range of primary amines, which contain different functional groups, were tolerated under these conditions. The mild reaction conditions, broad substrate scope, functional group tolerance, and operational simplicity make this deaminative coupling reaction a valuable method in organic syntheses.

Long non-coding RNA uc.80- overexpression promotes M2 polarization of microglias to ameliorate depression in rats.

Microglia polarization is associated with the pathogenesis of depression. A previous study shows that long non-coding RNA uc.80- is down-regulated in the hippocampus of depressed rats. Thus, this article aims to investigate the role of uc.80- in microglia polarization in depression. We first established depression model rats by chronic unpredictable mild stress (CUMS) regiment. We found that hippocampus of depressed rats exhibited an increase of M1 microglias and a decrease of M2 microglias. uc.80- was down-regulated in hippocampus of depressed rats. Furthermore, the detection of behaviouristics of depressed rats showed that uc.80- overexpression alleviated depression of rats. In addition, uc.80- overexpression promoted M2 polarization of microglias in vivo and in vitro. uc.80- overexpression led to a decrease in apoptosis of hippocampal neurons in vivo and in vitro. In conclusion, our study confirms that lncRNA uc.80- overexpression ameliorates depression in rats by promoting M2 polarization of microglias. Thus, our work suggests that uc.80- may be a target gene for depression treatment.

A comprehensive evaluation of single nucleotide polymorphisms associated with atrophic gastritis risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with atrophic gastritis (AG) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with AG. METHODS: To identify all associated studies of SNPs and AG published, databases had been searched through January 2020 from the databases of PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, Embase, the Chinese Science and Technology Periodical Database (VIP), Cochrane Library, and Wanfang databases. With the help of network meta-analysis and Thakkinstian algorithm, the best genetic model with the strongest correlation with AG was selected, the final result - matching to the noteworthy correlation - was obtained by referring to the false positive reporting rate (false positive report probability, FPRP). Based on STREGA's stated criteria, the methodological quality of the data we collected was valued. Both Stata 14.0 and GeMTC will be used for a comprehensive review of the system and will be used in our meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with AG susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with AG susceptibility. REGISTRATION: INPLASY202050016.

Up-regulation of paired-related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a.

Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired-related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha-smooth muscle actin (α-SMA). Both Prrx2 and Wnt5a gene expressions were up-regulated in mice following MI, accompanied with increased mRNA and protein levels of α-SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus-mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia-induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF-ß increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. Further, overexpression of Prrx2 or Wnt5a mirrored the effects of TGF-ß on cell differentiations of cardiac fibroblasts. Gene silence of Wnt5a also ablated cell differentiations induced by Prrx2 overexpression in cardiac fibroblasts. Mechanically, Prrx2 was able to bind with Wnt5a gene promoter to up-regulate Wnt5a gene expression. In conclusions, targeting Prrx2-Wnt5a signalling should be considered to improve cardiac remodelling in patients with ischaemic heart diseases.

Silver-Mediated Trifluoromethoxylation of (Hetero)aryldiazonium Tetrafluoroborates.

Here we report a silver-mediated trifluoromethoxylation of (hetero)aryldiazonium tetrafluoroborates by converting an aromatic amino group into an OCF3 group. This method, which can be considered to be a trifluoromethoxylation variation of the classic Sandmeyer-type reaction, uses readily available aryl and heteroaromatic amines as starting materials and AgOCF3 as trifluoromethoxylating reagents. The broad substrate scope and simple, mild reaction condition made this transformation a valuable method in constructing aryl-OCF3 bonds.

Data on SEM and TEM of controllable construction of ZnWO4 nanostructure with enhanced performance for photosensitized Cr(VI) reduction.

The data presented in this article are related to the research article entitled "Controllable construction of ZnWO4 nanostructure with enhanced performance for photosensitized Cr(VI) reduction"[1] published in Applied Surface Science. The data of SEM/TEM given in this manuscript shown the effect of the hydrothermal time on the morphology of zinc tungstate samples. The photocatalytic degradation activity of methyl orange (MO) over ZnWO4 nanorods obtained after 14 h hydrothermal process was investigated.

Selective Syntheses of Z-Alkenes via Photocatalyzed Decarboxylative Coupling of N-Hydroxyphthalimide Esters with Terminal Arylalkynes.

A novel, efficient Z-alkene synthesis via photocatalyzed decarboxylative couplings between terminal aryl alkynes and alkyl N-hydroxyphthalimide (NHPI) esters, which are derived from aliphatic carboxylic acids, is described. A wide range of primary, secondary, and tertiary carboxylates as well as α-amino acid and α-oxyacid-derived esters were employed as suitable substrates. The mild reaction conditions, broad substrate scope, functional group tolerance, and operational simplicity make this decarboxylative coupling reaction a valuable method in organic syntheses.

LncRNA PRNCR1 regulates CXCR4 expression to affect osteogenic differentiation and contribute to osteolysis after hip replacement.

BACKGROUND: Osteogenic differentiation plays an essential role in the pathogenesis of osteolysis, which is a complication of hip orthroplasty. The roles of lncRNA PRNCR1 in osteogenic differentiation and osteolysis were dissected in this study. METHODS: The expression of PRNCR1, miR-211-5p and C-X-C chemokine receptor-4 (CXCR4) protein in wear particles and mesenchymal stem cells (MSCs) were determined by qRT-PCR and Western blot, separately. The osteogenic differentiation degree of MSCs was assessed by ALP activity detection and ARS staining. Binding and interaction between RNA and protein were determined with RIP and RNA pull-down assay, respectively. Interaction between miR-211-5p and CXCR4 was examined by Dual luciferase reporter assay. RESULTS: PRNCR1 and CXCR4 were up-regulated in wear particles around prosthesis and in MSCs treated with PMMA, while miR-211-5p was down-regulated. Repression of PRNCR1 weakened the inhibitory effect of wear particles on osteogenic differentiation. PRNCR1 positively regulated CXCR4 through inhibiting miR-211-5p. Wear particles increased CXCR4 level through miR-211-5p to inhibit osteogenic differentiation of MSCs. Wear particles down-regulated miR-211-5p level through PRNCR1 to influence osteogenic differentiation of MSCs. CONCLUSION: LncRNA PRNCR1 up-regulates CXCR4 through targeting miR-211-5p, which affects osteogenic differentiation and thus contributing to osteolysis after hip replacement.

miR-411 suppresses acute spinal cord injury via downregulation of Fas ligand in rats.

OBJECTIVE: To explore the role of miR-411/FasL in acute spinal cord injury (ASCI). METHODS: The ASCI rat model was established, and expression of miR-411 and Fas ligand (FasL) was examined. Basso, Beattie and Bresnahan (BBB) score was used to evaluate the rats' neurological function. PC12 oxygen-glucose deprivation (OGD) model was also established. Gene manipulation (including miR-411 mimic or inhibitor) was used to modulate gene expression. Luciferase reporter assay was conducted to confirm the targeting relationship between miR-411 and FasL. Flow cytometry was applied in the measurement of PC12 cell apoptosis. Finally, the miR-411 mimic was injected into the vertebral canal of ASCI rats to determine the effects of miR-411 in vivo. RESULTS: Compared with sham group, the expression of miR-411 and FasL was significantly decreased and increased in ASCI group, respectively (P < 0.05). Similarly, the expression of miR-411 and FasL was significantly lower and higher in OGD group than that in control group, respectively (P < 0.05). miR-411 directly controlled the FasL expression. miR-411 mimic can dramatically reduce the increased percentage of apoptosis cells caused by OGD when comparing to mimic control, which was greatly reversed by the overexpression of FasL (P < 0.05). Further, the BBB score was significantly elevated in the miR-411 mimic group when comparing to mimic control group, with decreased FasL expression (P < 0.05). CONCLUSION: miR-411 mimic suppressed PC12 cell apoptosis via FasL, and relieved ASCI in rats.

LncRNA PRNCR1 regulates osteogenic differentiation in osteolysis after hip replacement by targeting miR-211-5p.

Background Osteogenic differentiation and osteolysis after hip replacement are both associated with bone metabolism. Interaction between the long non-coding RNA (lncRNA) prostate cancer non-coding RNA 1 (PRNCR1) and miR-211-5p was analyzed to illuminate their roles in osteogenic differentiation and osteolysis. Methods The expression of PRNCR1, miR-211-5p and C-X-C chemokine receptor-4 (CXCR4) protein in tissues and mesenchymal stem cells (MSCs) were determined by qRT-PCR and western blot, separately. The osteogenic differentiation was assessed with Alkaline phosphatase (ALP) activity detection and ARS staining. The endogenous expressions of genes were modulated by recombinant plasmid and cell transfection. Combination condition and interaction between RNA and protein were determined with RIP and RNA pull-down assay, respectively. Interaction between miR-211-5p and CXCR4 was examined with Dual luciferase reporter assay. Results PRNCR1 and CXCR4 were up-regulated in wear particles around prosthesis and in MSCs incubated with Polymethylmethacrylate (PMMA), while miR-211-5p was down-regulated. Repression of PRNCR1 weakened the inhibitory effect of wear particles on osteogenic differentiation. PRNCR1 positively regulated CXCR4 through inhibiting miR-211-5p. Wear particles regulated CXCR4 level through miR-211-5p to affect osteogenic differentiation of MSCs. Wear particles regulated the miR-211-5p level through PRNCR1 to affect osteogenic differentiation of MSCs. Conclusion LncRNA PRNCR1 up-regulates CXCR4 through inhibiting miR-211-5p, which inhibits osteogenic differentiation and thereby leading to osteolysis after hip replacement.

Solvent Effects: Syntheses of 3,3-Difluorooxindoles and 3-Fluorooxindoles from Hydrazonoindolin-2-one by Selectfluor.

Efficient syntheses of 3,3-difluorooxindoles and 3-fluorooxindoles via fluorination of hydrazonoindolin-2-one with Selectfluor are reported. Under different solvent conditions, this method produced 3,3-difluorooxindoles and 3-fluorooxindoles selectively. The broad substrate scope and mild reaction conditions make this transformation a valuable method in drug discovery and development.

Decarboxylative Fluorination of Electron-Rich Heteroaromatic Carboxylic Acids with Selectfluor.

A transition-metal-free decarboxylative fluorination of electron-rich five-membered heteroaromatics, including furan-, pyrazole-, isoxazole-, thiophene-, indole-, benzofuran- and indazolecarboxylic acids, with Selectfluor is reported. Fluorinated dimer products were observed for nitrogen-containing heteroaromatic carboxylic acids, such as indole and pyrazole. An effective method has been developed to synthesize the monomer of 2- and 3-fluoroindoles with Li2CO3 as base at low temperature.

GluN2B-containing NMDA receptors contribute to the beneficial effects of hydrogen sulfide on cognitive and synaptic plasticity deficits in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is the most common type of clinical dementia. Previous studies have demonstrated that hydrogen sulfide (H2S) is implicated with the pathology of AD, and exogenous H2S attenuates spatial memory impairments in AD animal models. However, the molecular mechanism by which H2S improves cognition in AD has not been fully explored. Here, we report that chronic administration of sodium hydrosulfide (NaHS, a H2S donor) elevated hippocampal H2S levels and enhanced hippocampus-dependent contextual fear memory and novel object recognition in amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice. In parallel with these behavioral results, treating transgenic mice with NaHS reversed impaired hippocampal long-term potentiation (LTP), which is deemed as the neurobiological basis of learning and memory. At the molecular level, we found that treatment with NaHS did not affect the expression of the GluN1 and GluN2A subunits of NMDA receptor (NMDAR), but did prevent the downregulation of GluN2B subunit and restored its synaptic abundance, response and downstream signaling in the hippocampus in transgenic mice. Moreover, applying Ro 25-6981, a specific GluN2B antagonist, abolished the beneficial effects of NaHS on cognitive performance and hippocampal LTP in transgenic mice. Collectively, our results indicate that H2S can reverse cognitive and synaptic plasticity deficits in AD model mice by restoring surface GluN2B expression and the function of GluN2B-containing NMDARs.