Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.

Numerical investigation of sinusoidal pulsating gas intake to intensify the gas-slag momentum transfer in the top-blown smelting furnace

The variation characteristics of bubble morphology and the thermal-physical properties of bubble boundary in the top-blown smelting furnace were explored by means of the computational fluid dynamics method.The essential aspects of the fluid phase(e.g.,splashing volume,dead zone of copper slag,and gas penetration depth)were explored together with the effect of sinusoidal pulsating gas intake on the momentum-transfer performance between phases.The results illustrated that two relatively larger vortices and two smaller vortices appear in the bubble waist and below the lance,respectively.The expansion of larger ones as well as the shrinking of smaller ones combine to cause the contraction of the bubble waist.Compared to the results of the case with a fixed gas injection velocity(V_(g)=58 m/s),the splashing volume and dead zone volume of the slag under the V_(g)=58+10sin(2πt)condition are reduced by 24.9%and 23.5%,respectively,where t represents the instant time.Gas penetration depth and slag motion velocity of the latter are 1.03 and 1.31 times high-er than those of the former,respectively.

Therapeutic Effect of Rhodopseudomonas palustris-Bioconverted Extract of Lycium barbarum on Rats with Lead Exposure

Lead is a ubiquitous pollutant and Pb pollution is a global public health problem.Lead has been reported to induce multiple adverse effects,including reproductive toxicity,neurotoxicity,carcinogenicity,nephrotoxicity,immunotoxicity,and hypertension[1].The traditional medical treatment available for Pb poisoning is chelation,which can save lives in individuals with very high blood Pb levels.The commonly used chelating agents include CaNa2EDTA and meso-2,3-dimercaptosuccinic acid.However,chelation therapy has strong short-term effects on the overall long-term management of Pb exposure.

Recent advancements in continuously scalable conversion-ratio switched-capacitor converter

Switched-capacitor(SC)DC-DC converter[1]is an impor-tant alternative to inductive DC-DC converter,in terms of removing the bulky power inductor.Hence,it is widely used in low-profile,low-power applications,such as the internet of things(IoT)sensor nodes and energy harvesting[2].Mean-while,considering that capacitor has a much higher energy density than inductor,high-power applications.

Energy-Efficient Implementation of BCD to Excess-3 Code Converter for Nano-Communication Using QCA Technology

Code converters are essential in digital nano communication;therefore,a low-complexity optimal QCA layout for a BCD to Excess-3 code converter has been proposed in this paper.A QCA clockphase-based design technique was adopted to investigate integration with other complicated circuits.Using a unique XOR gate,the recommended circuit’s cell complexity has been decreased.The findings produced using the QCADesigner-2.0.3,a reliable simulation tool,prove the effectiveness of the current structure over earlier designs by considering the number of cells deployed,the area occupied,and the latency as design metrics.In addition,the popular tool QCAPro was used to estimate the energy dissipation of the proposed design.The proposed technique reduces the occupied space by∼40%,improves cell complexity by∼20%,and reduces energy dissipation by∼1.8 times(atγ=1.5EK)compared to the current scalable designs.This paper also studied the suggested structure’s energy dissipation and compared it to existing works for a better performance evaluation.

Robust optical mode converter based on topological waveguide arrays

Optical mode converters are essential for enhancing the capacity of optical communication systems. However, fabrication errors restrict the further improvement of conventional mode converters. To address this challenge, we have designed an on-chip TE0–TE1mode converter based on topologically protected waveguide arrays. The simulation results demonstrate that the converter exhibits a mode coupling efficiency of 93.5% near 1550 nm and can tolerate a relative fabrication error of 30%. Our design approach can be extended to enhance the robustness for other integrated photonic devices, beneficial for future development of optical network systems.

ANovel Non-Isolated Cubic DC-DC Converter with High Voltage Gain for Renewable Energy Power Generation System

In recent years,switched inductor(SL)technology,switched capacitor(SC)technology,and switched inductor-capacitor(SL-SC)technology have been widely applied to optimize and improve DC-DC boost converters,which can effectively enhance voltage gain and reduce device stress.To address the issue of low output voltage in current renewable energy power generation systems,this study proposes a novel non-isolated cubic high-gain DC-DC converter based on the traditional quadratic DC-DC boost converter by incorporating a SC and a SL-SC unit.Firstly,the proposed converter’s details are elaborated,including its topology structure,operating mode,voltage gain,device stress,and power loss.Subsequently,a comparative analysis is conducted on the voltage gain and device stress between the proposed converter and other high-gain converters.Then,a closed-loop simulation system is constructed to obtain simulation waveforms of various devices and explore the dynamic performance.Finally,an experimental prototype is built,experimental waveforms are obtained,and the experimental dynamic performance and conversion efficiency are analyzed.The theoretical analysis’s correctness is verified through simulation and experimental results.The proposed converter has advantages such as high voltage gain,low device stress,high conversion efficiency,simple control,and wide input voltage range,achieving a good balance between voltage gain,device stress,and power loss.The proposed converter is well-suited for renewable energy systems and holds theoretical significance and practical value in renewable energy applications.It provides an effective solution to the issue of low output voltage in renewable energy power generation systems.

An Adaptive Control Strategy for Energy Storage Interface Converter Based on Analogous Virtual Synchronous Generator

In the DC microgrid,the lack of inertia and damping in power electronic converters results in poor stability of DC bus voltage and low inertia of the DC microgrid during fluctuations in load and photovoltaic power.To address this issue,the application of a virtual synchronous generator(VSG)in grid-connected inverters control is referenced and proposes a control strategy called the analogous virtual synchronous generator(AVSG)control strategy for the interface DC/DC converter of the battery in the microgrid.Besides,a flexible parameter adaptive control method is introduced to further enhance the inertial behavior of the AVSG control.Firstly,a theoretical analysis is conducted on the various components of the DC microgrid,the structure of analogous virtual synchronous generator,and the control structure’s main parameters related to the DC microgrid’s inertial behavior.Secondly,the voltage change rate tracking coefficient is introduced to adjust the change of the virtual capacitance and damping coefficient flexibility,which further strengthens the inertia trend of the DC microgrid.Additionally,a small-signal modeling approach is used to analyze the approximate range of the AVSG’s main parameters ensuring system stability.Finally,conduct a simulation analysis by building the model of the DC microgrid system with photovoltaic(PV)and battery energy storage(BES)in MATLAB/Simulink.Simulation results from different scenarios have verified that the AVSG control introduces fixed inertia and damping into the droop control of the battery,resulting in a certain level of inertia enhancement.Furthermore,the additional adaptive control strategy built upon the AVSG control provides better and flexible inertial support for the DC microgrid,further enhances the stability of the DC bus voltage,and has a more positive impact on the battery performance.

Expression of interleukin 1β converting enzyme in 5-FU induced apoptosis in esophageal carcinoma cells

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A Novel Angiotensin I Converting Enzyme Inhibitory Peptide from the Milk Casein:Virtual Screening and Docking Studies

Angiotensin I converting enzyme （ACE） plays an important physiological role in the regulation of hypertension. In this study, we applied virtual screening to discover a novel angiotensin I converting enzyme inhibitory peptides from milk casein. One potential hit was identified based on docking scores, subsequently confirmed by activity studies in vitro （IC50=20.85 μmol L-1）. The proposed peptide in this study contains a unique sequence, Lys-Val-Leu-Ile-Leu-Ala. Moreover, we performed the docking studies to understand the binding mode between the enzyme and peptide hit.

Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough:A meta-analysis

AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.METHODS:We conducted a search in PubMed,EM-BASE,Cinahl,and the Cochrane Database without language limitation.A database of 11 studies on ACEI-related cough,with detailed information regarding ACE I/D or bradykinin B 2 receptor polymorphisms,was created.Eligible studies were synthesized using meta-analysis methods,including cumulative meta-analysis.A subgroup analysis was also performed using ethnicity.RESULTS:Six studies were included on ACE I/D poly-morphism (398 Caucasians,723 East Asians),and three studies were included on bradykinin B 2 receptor poly-morphism (300 East Asians).The distribution of ACE genotypes showed significant differences in the entire population (P=0.004) and in East Asians (P=0.005)but not in Caucasians (P=0.23).Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR)=1.49 (1.11-2.02)].The meta-analysis with a random effects model showed a significant associa-tion between ACE allele I/D and ACEI-related cough [random effects (RE) OR=1.49 (1.11-2.02),P=0.009] in East Asians,but not in Caucasians [RE OR=0.90 (0.60-1.35)].The allelic frequencies of the bradykinin B 2 receptor gene were significantly different [OR=2.25 (1.42-3.57)].The distributions of the T/C genotypes of the bradykinin B 2 receptor gene were significantly dif-ferent (χ 2=8.366,P=0.015).The meta-analyses re-vealed that there was a significant association between the bradykinin B 2 receptor allele and ACEI-related cough in East Asians [RE OR=2.29 (1.42-3.69),P=0.001].CONCLUSION:ACE I/D and Bradykinin B 2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians,but a negative association be-tween ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

Effects of Yinchenhao Decoction on Self-regulation of Renin-angiotensin System by Targeting Angiotensin Converting Enzyme 2 in Bile Duct-ligated Rat Liver

Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.

Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%-15% of nephrotic syndrome cases are non-responders of steroid treatment(SRNS).Angiotensin converting enzyme(ACE)(I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE(I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome(162 boys and 98 girls) and 218(140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE(I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases(minimal change disease, n = 51;focal segmental glomerulosclerosis, n = 27;diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease/focal segmental glomerulosclerosis groups and observed that the ACE’D’ allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the ’Ⅰ’ allele was assessed as having very weak association in cases of minimal change disease. ’Ⅱ’ genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of’ID’ genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE(I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.

Correlation of angiotensin converting enzyme gene polymorphism with perioperative myocardial protection under extracorporeal circulation

Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 【cTnⅠ),creatine kinase isozymes(CK-MB) and muscle red protein(Myo) after cardiopulmonary bypass(CPB),and to investigate the association of polymorphisms in angiotensin converting enzyme genes and myocardial injury.Methods:Sixty-three patients suffered from rheumatic mitral stenosis and scheduled for mitral valve replacement with CPB, were randomly divided into three groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure the expression of ACE,AngⅡ,cTnⅠ,CK-MB, Myo.Results:The level of ACE during and after CPB were significantly higher than those before CPB(P【0.05).As extension of CPB time,the expression of ACE was increased.The level of cTnⅠ, CK-MB,Myo after CPB were significantly higher than those before CPB(P【0.05).The level of cTnⅠ,CK-MB and Myo were highest at T7,T6 and T5 and T7,respectively.The level of ACE,AngⅡ,cTnⅠin patients with DD genotype was significantly higher than the ID andⅡgenotype(P【 0.05).Besides,the level of ACE,AngⅡin patients with ID genotype was significantly higher than the II(P【 0.05).Conclusions:There is certain correlation between CPB perioperative midterm ACE and cTnⅠ,Myo,CK-MB.ACE DD genotype is a susceptibility gene of the CPB perioperative myocardial injury.

Origin and genomic characteristics of SARS-CoV-2 and its interaction with angiotensin converting enzyme type 2 receptors, focusing on the gastrointestinal tract

The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis

The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.

Long-term Administration of Angiotension-Converting Enzyme Inhibitor Improves the Outcome of Chronic Heart Failure in Senile Patients

One hundred and sixteen senile patients (older than 65 years) with chronic heart failure (CHF) were analyzed retrospectively in order to verify if old patients with CHF would benefit from long term (one year) angiotension converting enzym e inhibitor (ACEI) treatment. The frequency of drugs (including ACEI, digitalis and diuretic) used was stratified into four degrees accordingly. Develop ment of the CHF was scored with regard to relapse rate and severity of this dise ase. Stepwise regression analysis was applied to explore the relationship betwee n the scored outcome of CHF and the frequency of individual drug administration. A significant relationship of the scored outcome of CHF to the frequency of ACE I usage but not to digitalis nor to diuretics was found (partial coefficient of the correlation r =0.42, P =0.002). It was concluded that the long term a dministration of ACEI improves the outcome of CHF in senile patients.

Liquid Chromatographic Assay of Peptides Activity with Inhibiting Angiotensin Converting Enzyme

A rapid, simple and interference-free method was developed to evaluate the inhibitory activity of hydrolyzed peptides from egg white protein against the angiotensin-converting enzyme. The total reaction volume was 60 μL, saving the cost. The assay was based on a HPLC separation and quantification of the synthetic substrate hippuryl-L-histidyl-L-leucine and its hydrolyzed product-hippuric acid; the separation was performed on a C18 column eluted by a mobile phase of acetonitrile/water（0.5% TFA） at a volume ratio of 25：75. At a signal to noise ratio（S/N） of 10, the detective limit of the quantitation of hippuric acid was （0.4600±0.0097） μmol/L. The standard curve shows a linear response with a slope of 49488 and a correlation coefficient of 0.9995. The assay was adequate for the study of ACE inhibition by Captopril and peptides derived from food protein, and showed a very good correlation with the previous methods.

Comparison of Properties of Tumor Necrosis Factor-α Converting Enzyme (TACE) and Some Matrix Metalloproteases (MMPs) in Catalytic Domains

The crystal structural data of TACE, MMP-1, MMP-2, MMP-3 and MMP-9 were obtained from PDB database, and then their catalytic domains＇ properties including conformation, molecular surface hydrophobicity and electrostatic potential were analyzed and compared by using Insight II molecular modeling software. It was found that the conformation and molecular surface hydrophobicity of catalytic domains of TACE and MMPs were not obviously different, but the molecular surface electrostatic potential of catalytic domain of TACE＇ and MMPs had obvious differences. The findings are helpful in the Rational Drug Design of TACE selective inhibitor.