Objective: In March 2022, more than 600 million cases of Corona Virus Disease 2019 (COVID-19) and about 6 million deaths have been reported worldwide. Unfortunately, while effective antiviral therapy has not yet been available, chloroquine (CQ)/hydroxychloroquine (HCQ) has been considered an option for the treatment of COVID-19. While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients' lives, controversial results have also been reported. One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval (LQT), an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias. Yet, the mechanisms for this cardiotoxicity of HCQ remained incompletely understood. Materials and methods: Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes. HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene (hERG) K+ channels were used for whole-cell patch-clamp recordings of hERG K+ channel current (IhERG). Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels, respectively. Results: electrocardiogram (ECG) recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits. Whole-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation state. HCQ suppressed the expression of hERG and hindered the formation of the heat shock protein 90 (Hsp90)/hERG complex. Moreover, the expression levels of connexin 43 (CX43) and Kir2.1, the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias, were decreased by HCQ, while those of Cav1.2, the main Ca2+ handling proteins, remained unchanged and SERCA2a was increased. Conclusion: HCQ could induce LQT but did not induce arrhythmias, and whether it is suitable for the treatment of COVID-19 requires more rigorous investigations and validations in the future.

A growing number of companies within the cheese-making industry are now using high-protein (e.g., 4-5%) milks to increase cheese yield. Previous studies have suggested that cheeses made from high-protein (both casein and whey protein; WP) milks may ripen more slowly; one suggested explanation is inhibition of residual rennet activity due to elevated WP levels. We explored the use of microfiltration (MF) to concentrate milk for cheese-making, as that would allow us to concentrate the casein while varying the WP content. Our objective was to determine if reducing the level of WP in concentrated cheese milk had any impact on cheese characteristics, including ripening, texture, and nutritional profile. Three types of 5% casein standardized and pasteurized cheese milks were prepared that had various casein:true protein (CN:TP) ratios: (a) control with CN:TP 83:100, (b) 35% WP reduced, 89:100 CN:TP, and (c) 70% WP reduced, 95:100 CN:TP. Standardized milks were preacidified to pH 6.2 with dilute lactic acid during cheese-making. Composition, proteolysis, textural, rheological, and sensory properties of cheeses were monitored over a 9-mo ripening period. The lactose, total solids, total protein, and WP contents in the 5% casein concentrated milks were reduced with increasing levels of WP removal. All milks had similar casein and total calcium levels. Cheeses had similar compositions, but, as expected, lower WP levels were observed in the cheeses where WP depletion by MF was performed on the cheese milks. Cheese yield and nitrogen recoveries were highest in cheese made with the 95:100 CN:TP milk. These enhanced recoveries were due to the higher fraction of nitrogen being casein-based solids. Microfiltration depletion of WP did not affect pH, sensory attributes, or insoluble calcium content of cheese. Proteolysis (the amount of pH 4.6 soluble nitrogen) was lower in control cheeses compared with WP-reduced cheeses. During ripening, the hardness values and the temperature of the crossover point, an indicator of the melting point of the cheese, were higher in the control cheese. It was thus likely that the higher residual WP content in the control cheese inhibited proteolysis during ripening, and the lower breakdown rate resulted in its higher hardness and melting point. There were no major differences in the concentrations of key nutrients with this WP depletion method. Cheese milk concentration by MF provides the benefit of more typical ripening rates.

心肌纤维化是多种心血管疾病的重要病理特征和改变,包括心肌梗死和心衰等.目前,心肌纤维化的分子机制尚不明确,且无有效的治疗药物.非编码RNAs是一类不具有编码蛋白能力的RNAs,可以在转录调控、转录后调控和表观遗传学水平影响基因的表达,参与细胞的生物学过程.非编码RNAs通过影响心脏成纤维细胞增殖和转化等过程参与心肌纤维化的调控,可作为心肌纤维化的潜在干预靶点和生物标记物,为心肌纤维化相关疾病的治疗提供新的策略和方法.本文旨在对非编码RNAs在心肌纤维化中的功能和机制的研究进展进行综述.

OBJECTIVE: To study the influence of micro ribonucleic acid (miR)-26a on myocardial cell apoptosis in rats with acute myocardial infarction (AMI) through the glycogen synthase kinase 3 beta (GSK-3 beta) pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12), and miR-26a mimics group (n=12). Only the heart was exposed, and normal saline was intraperitoneally injected postoperatively in sham group, and the model of AMI was prepared in model group. Besides, after modeling, miR-26a mimics were injected into the left ventricle in miR-26a mimics group. At 48 h after operation, sampling was performed. Then, the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax), as well as the protein expression of phosphorylated GSK-3 beta (p-GSK-3 beta) were detected via immunohistochemistry and Western blotting, respectively. Moreover, the expression level of miR-26a was measured via quantitative polymerase chain reaction (qPCR), and cell apoptosis was evaluated using terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. RESULTS: Compared with those in sham group, the expression level of Bax was substantially raised, but that of Bcl-2 was notably lowered in model group and miR-26 mimics group (p<0.05), and miR-26 mimics group had a markedly lower expression level of Bax and a remarkably higher expression level of Bcl-2 than model group (p<0.05). According to Western blotting results, the protein expression level of p-GSK-3p in model and miR-26a mimics groups was considerably higher than that in sham group (p<0.05), and miR-26a mimics group exhibited a notably higher protein expression level of p-GSK-3 beta than model group (p<0.05). In comparison with that in sham group, the expression level of miR-26a rose markedly in both model group and miR-26a mimics group (p<0.05), and its expression level in miR-26a mimics group was dramatically higher than that in model group (p<0.05). Additionally, the TUNEL-positive cells were considerably increased in both model group and miR-26a mimics group in comparison with that in sham group (p<0.05), and miR-26a mimics group had markedly fewer TUNEL-positive cells than model group (p<0.05). CONCLUSIONS: MiR-26a activates the GSK-3 beta signaling pathway to inhibit myocardial cell apoptosis after AMI.

Some European dairies use low concentration factor microfiltration (MF) in their cheese plants. Removal of whey protein (WP) from milk before cheesemaking using microfiltration without concentration provides the opportunity to produce a value-added by-product, milk-derived whey. However, few studies have focused on the effects on cheese properties caused by the depletion of WP from cheese milk. Most studies have concentrated cheese milk using MF in addition to depletion of WP. In our approach, cheese milk was not concentrated during WP depletion using MF. We wanted to quantify residual WP levels in cheese made from MF milk and to explore whether WP depletion from milk would influence functionality, nutritional profile, and cheese quality during ripening. Casein (CN) contents for all milks were kept at ∼2.5%, to eliminate the confounding factor of concentration of CN, which was observed in some previous MF studies. Cheese milks had similar ratios of CN to fat. Three standardized milks were produced with various CN:true protein (TP) ratios: (a) control with a CN:TP ratio of 83:100, (b) 35% WP depletion, 89:100 CN:TP, and (c) 70% WP depletion, 95:100 CN:TP. Cheddar cheeses were made from MF milk with various WP depletion levels and aged for 9 mo, and their functionality was evaluated during ripening. We found no major differences in cheese composition or pH values between samples. Cheese yield, solids recovery, and nitrogen recovery were slightly higher in the 95:100 CN:TP cheeses compared with the control. These enhanced recoveries reflect that MF-treated milk started with a higher fraction of CN-based protein solids, rather than WP solids. The standardized milk from the 95:100 CN:TP treatment also had a slightly higher fat content compared with the control, likely helping to increase cheese yield. Rheological properties of cheeses during heating were similar between treatments. Hardness initially decreased with age for all cheeses due to proteolysis or solubilization, or both, of calcium phosphate. Maximum loss tangent (LT), an index of cheese meltability, was slightly lower for the control cheese until 30 d of ripening, but after 30 d, all treatments exhibited similar maximum LT values. The temperature where LT = 1 (crossover temperature), an index of softening point during heating, was slightly lower for MF cheese compared with the control cheeses during ripening. Microfiltration treatment had no significant influence on proteolysis. Sensory properties were similar between the cheeses, except for bitterness. Bitterness intensity was slightly lower in the MF cheeses than in the control cheeses and increased in all cheeses during ripening. We detected no major differences in the concentrations of key nutrients or vitamins between the various cheeses. Depletion of WP in cheese milk by MF did not negatively affect cheese quality, or its nutritional profile, and resulted in similar cheesemaking yields.

MicroRNA let-7家族为最早发现于秀丽隐杆线虫的microRNA之一,由于其在心血管组织中高表达,因此let-7在心血管疾病中发挥的功能和调控作用一直受到科研工作者的关注.随着对let-7研究的不断深入,let-7靶向作用的基因也不断被更新报道,除较早发现的靶基因Toll样受体4(Toll-like receptor 4,TLR4)和Bcl-xL以外,最新发现的靶基因如β1-肾上腺素受体(β1-adrenergic receptor,β1-AR)、钙调蛋白基因(calmodulin gene,CaM)以及相应的信号通路在心血管疾病中也发挥着重要的调控作用,说明let-7有可能成为心血管疾病的临床诊断和治疗的新靶点.

Hypertension is a public health issue around the world.At present,Canada is one of the few countries that have achieved remarkable success in the prevention and control of hypertension.Canada has accumulated a considerable amount of advanced experience in the control of hypertension and in the implementation of effective measures against it.This article introduces the prevalence of hypertension in Canada and the development of control strategies and measures against hypertension in Canada,including the Canadian Hypertension Society,the Canadian Hypertensive Education Program,public policies,community interventions,and healthcare systems.We summarize these advanced experiences in order to provide a policy-making basis for the development of hypertension prevention and control in China.

The aligned W18O49 nanowire clusters were synthesized via a facile and economic ethanol-assisted hydrothermal method using peroxopolytungstic acid as precursor. Results show that the as-prepared W18O49 exhibits a high yield and ultrathin structure with preferential growth direction along [0 1 0]. The amount of peroxopolytungstic acid and reaction time play significant role on the morphology of W18O49 nanowires. The nanowires have unique structure, high degree of crystallinity, large specific surface area, and large number of defects such as oxygen vacancies, which are responsible for their high photocatalytic performance for degradation of methylene blue. The photocatalytic conversion of methylene blue can reach above 98% after degradation. W18O49 also exhibits good photodegradation stability after five cycles of reuse. The results demonstrate that the as-prepared W18O49 nanowire clusters are expected to be a promising material for applications in the field of environment. (C) 2017 Elsevier B.V. All rights reserved.

Background The polyphenol resveratrol (Rev) has been reported to exhibit cardioprotective effects, such as inhibition of TAC (transverse aortic constriction) or isoprenaline (ISO)‐induced hypertrophy. Micro RNA ‐155 (miR‐155) was found to be decreased in hypertrophic myocardium, which could be further reduced by pretreatment of Rev. The study was designed to investigate the molecular effects of miR‐155 on cardiac hypertrophy, focusing on the role of breast cancer type 1 susceptibility protein ( BRCA 1). Methods and Results We demonstrated that Rev alleviated severity of hypertrophic myocardium in a mice model of cardiac hypertrophy by TAC treatment. Down‐regulation of miR‐155 was observed in pressure overload– or ISO ‐induced hypertrophic cardiomyoctyes. Interestingly, administration of Rev substantially attenuated miR‐155 level in cardiomyocytes. In agreement with its miR‐155 reducing effect, Rev relieved cardiac hypertrophy and restored cardiac function by activation of BRCA 1 in cardiomyoctyes. Our results further revealed that forkhead box O3a (FoxO3a) was a miR‐155 target in the heart. And miR‐155 directly repressed FoxO3a, whose expression was mitigated in miR‐155 agomir and mimic treatment in vivo and in vitro. Conclusions We conclude that BRCA 1 inactivation can increase expression of miR‐155, contributing to cardiac hypertrophy. And Rev produces their beneficial effects partially by down‐regulating miR‐155 expression, which might be a novel strategy for treatment of cardiac hypertrophy.

Bioactive peptides, including angiotensin-I-converting enzyme-inhibitory (ACEI) peptides, were investigated in commercially produced Wisconsin Cheddar cheeses that ranged in age from ≤ 6d to more than 2 yr. The ACEI activity of cheese was determined in water-soluble extracts (WSE) that were fractionated for components with molecular weight (MW) ≤ 3,000 Da, and peptides identified using HPLC and tandem mass spectrometry. The number of types of bioactive peptides increased with an increase in ripening time. Six of the identified ACEI peptides, Ile-Pro-Pro (IPP), Val-Pro-Pro (VPP), Glu-Lys-Asp-Glu-Arg-Phe (EKDERF), Val-Arg-Tyr-Leu (VRYL), Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn (YPFPGPIPN), and Phe-Phe-Val-Ala-Pro (FFVAP), with known high ACEI activity (low IC50 values, the concentration needed to inhibit ACE to 50% of its original activity) were synthesized and used to quantify the amounts of these peptides in various cheese extracts. The concentrations of these 6 ACEI peptides increased up to a certain stage of ripening. The maximum contents of IPP, VPP, and EKDERF were 2.8, 7.4, and 5.3mg/100 g of cheese, respectively, and these levels were found in a 1-yr-old Cheddar cheese sample. The maximum content of VRYL (7.5mg/100 g of cheese) was found in a 2-yr-old Cheddar cheese sample, whereas the maximum content of YPFPGPIPN (6.8 mg/100 g of cheese) was found in a 6-mo-old Cheddar cheese sample. Trace amounts of FFVAP were found in these cheeses. Aged Cheddar cheese was found to be a rich source of ACEI peptides even though large differences exist between cheeses from different manufacturers.

Supported Pt-based alloy nanoparticles have attracted greater attention in catalysis due to their high activity, reduced cost, and easy recycling in chemical reactions. In this work, mesoporous SiO2 microspheres were employed as support to immobilize PtNi alloy nanocatalysts with different mass ratios of Pt and Ni (1:0, 3:1, 1:1, 1:3 and 0:1) by a facile in situ one-step reduction in the absence of any capping agent. SEM, EDS, TEM, FTIR, XRD, ICP-AES, XPS and nitrogen adsorption/desorption analysis were employed to systematically investigate the morphology and structure of the obtained SiO2 microspheres and SiO2/PtNi nanocatalysts. Results show that uniform PtNi nanoparticles can be homogeneously and firmly embedded into the surface of SiO2 microspheres. When the as-prepared SiO2/PtNi nanocatalysts were used in the reduction process of p-nitrophenol to p-aminophenol, the nanocatalyst with Pt and Ni mass ratio of 1:3 showed the highest catalytic activity (TOF of 5.35 × 1018 molecules⋅g −1⋅s −1) and could transform p-nitrophenol to p-aminophenol completely within 5 min. The SiO2/PtNi nanocatalyst can also maintain high catalytic activity in the fourth cycle, implying its excellent stability during catalysis.

The peanut-shaped monoclinic scheelite BiVO4 crystals were synthesized via a facile one step hydrothermal method without using any templates, followed by annealing at different temperatures. The as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Brunauer-Emmet-Teller (BET) and UV-vis diffuse reflectance spectra (DRS), showing that the annealing procedure could not only change the surface morphology and crystallinity of BiVO4 but also increase the specific surface area without damaging the peanut shape. The band gap values of the samples annealed at different temperatures could be reduced to 2.44-2.46 eV as compare with that of 2.47 eV of the original sample. The photocatalytic activities of BiVO4 crystals were evaluated by degradation of methylene blue in aqueous solution under artificial solar-light. Results demonstrated that the sample annealed at 450 degrees C exhibited the highest activity, and the photocatalytic conversion of methylene blue could reach above 94% after 150 min of irradiation. (C) 2015 Elsevier Ltd. All rights reserved.

Peanut shells were transformed into porous carbon with a high surface area through a simple ZnCl2-molten salt synthesis process.

The monoclinic scheelite BiVO4 crystals with peanut-like, oval, twin-quadrangle and twin-four-pointed star morphologies were synthesized via a facile one step hydrothermal method by using sodium citrate as the chelating agent. The X-ray diffraction and scanning electron microscopy were employed to elucidate the structures and mophologies of the as-prepared BiVO4 samples. The results showed that the formation of m-BiVO4 with different morphologies relied on the pH value of the precursor solution. The band gaps values (Eg) of all the BiVO4 samples were around 2.37–2.45 eV according to the UV–vis diffuse reflectance spectrum, which indicated that samples could strongly absorb in the visible light region. The photocatalytic activities of BiVO4 crystals were evaluated by degradation of MB in aqueous solution under artificial solar-light. The BiVO4 samples obtained at different pH values showed different photocatalytic activities during the sunlight-driven photodegradation of methylene blue (MB). The sample with peanut-like-shape prepared at pH=1 exhibited the highest activity, and the photocatalytic conversion could reach above 90% after 3 h of irradiation. The result suggested that m-BiVO4 with peanut-like-shape could be used as an effective photocatalyst in practical application for organic pollutants degradation.

心律失常是心脏疾病常见的病症之一,不仅引起心脏功能障碍还可引起心源性猝死.MicroRNAs(miRNAs)是一类长度约22 nt的单链非编码RNA.MiRNAs广泛参与细胞增殖、凋亡、分化、氧化应激等病理生理过程.MiRNAs不仅与心肌梗死、心肌肥厚及心肌纤维化等疾病发生密切相关,更与多种心脏病理状态下心脏电重构和心律失常的发生密切相关.近年来越来越多的研究证实miR-1、miR-328、let-7、miR-26、miR-208a等在心律失常发生发展过程中发挥了重要作用,并有望成为心律失常预警、诊断和治疗的新靶点.在这里阐述了这些miRNAs在心房纤颤、室性心律失常及心肌纤维化发生中的作用及意义.