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.

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.

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

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

AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 fluorouracil (5 FU) were observed under light and electron microscope. Expression of ICE in the tumor cells exposed to 5 FU was examined by the immunocytochemical method. RESULTS The cells treated with 5 FU displayed disappearance of nucleoli, chromatin gathering under nuclear envelope, karyorrhexis, budding and the formation of apoptotic bodies. The expression of ICE was negative in control cells, and 5 FU could induce the ICE expression in Eca 109 cells undergoing apoptosis. The number and the staining intensity of positive cells increased with the extension of action time. CONCLUSION 5 FU may induce apoptosis in human esophageal carcinoma Eca 109 cells; ICE gene may be involved in the regulation of 5 FU induced apoptosis; and ICE protein may mediate apoptosis induced by 5 FU.

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.

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.

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.

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.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.

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.

Soil Erosion Control Degree of the Project of Converting Farmland to Forest in Mountainous Areas at China's Southwest Border:A Case Study in Mangshi,Yunnan Province

There have been few in-depth quantitative studies on soil erosion control and the ecological effects of land use changes. Soil erosion is the first eco-environmental problem particularly in mountainous areas. A major problem in the conversion of farmland to forest is to control soil erosion and improve ecological environment and thus to improve land use sustainability. We report results of calculation and analysis on soil erosion from converted farmland parcels in city of Mangshi （near the SW frontier of China） and the surrounding areas before and after the nine-year （2000-2009） project of converting farmland to forest. There was increased water conservation effect, as a result of decreased soil erosion. The average erosion modulus of the farmland returning to eco-friendly uses decreased by 5,535.59 t/km2·a and the control degree of soil erosion modulus reached 71.00%. The increased soil erosion after the returning in the typical sample area ＂did not drop, but increased＂ as the terraced fields decreased but sloping farmland inereased and yet woodland decreased.

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.

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.

Neural network based on adaptive chaotic gradient descending optimization algorithm and its application in matte converting process

An adaptive chaotic gradient descending optimization algorithm for single objective optimization was presented. A local minimum judged by two rules was obtained by an improved mutative-step gradient descending method. A new optimal minimum was obtained to replace the local minimum by mutative-scale chaotic search algorithm whose scales are magnified gradually from a small scale in order to escape local minima. The global optimal value was attained by repeatedly iterating. At last, a BP (back-propagation) neural network model for forecasting slag output in matte converting was established. The algorithm was used to train the weights of the BP neural network model. The simulation results with a training data set of 400 samples show that the training process can be finished within 300 steps to obtain the global optimal value, and escape local minima effectively. An optimization system for operation parameters, which includes the forecasting model, is achieved, in which the output of converter increases by 6.0%, and the amount of the treated cool materials rises by 7.8% in the matte converting process.

POLYMORPHISM OF ANGIOTENSIN CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness. Methods. A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0 05; odd ratio 4 98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P<0 05; odd ratio 3 8). Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (73 78% vs 56 56%, P<0 05; 79 19% vs 69 29%, P<0 05, respectively). Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.

Expression of tumor necrosis factor-alpha converting enzyme in liver regeneration after partial hepatectomy

AIM:To study the expression of tumor necrosis factor- alpha converting enzyme (TACE) and evaluate its significance in liver regeneration after partial hepatectomy in vivo. METHODS: Male SD rats underwent 70% partial hepatec- tomy. The remaining liver and spleen tissue samples were collected at indicated time points after hepatectomy. TACE expression was investigated by Western blotting, immunohistochemistry, and serial section immunostaining. RESULTS: Expression of TACE in liver and spleen tissues after partial hepatectomy was a time-dependent alteration, reaching a maximal level between 24 and 48 h and remaining elevated for more than 168 h. TACE protein was localized to mononuclear cells (MNC), which infiltrated the liver from the spleen after hepatectomy. The kinetics of TACE expression was in accordance with the number of TACE-staining MNCs and synchronized with those of transforming growth factor-α (TGFα). In addition, TACE-staining MNC partially overlapped with CD3+ T lymphocytes. CONCLUSION: TACE may be involved in liver regenera- tion by pathway mediated with TGFα-EGFR in the cell- cycle progressive phase in vivo. TACE production and effect by paracrine may be a pathway of involvement in liver regeneration for the activated CD3+ T lymphocytes.

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.

Purification and Characterization of Angiotensin I Converting Enzyme Inhibition Peptides from Sandworm Sipunculus nudus

Three angiotensin I converting enzyme(ACE) inhibition peptides were isolated from sandworm Sipunculus nudus protein hydrolysate prepared using protamex. Consecutive purification methods, including size exclusion chromatography and reverse-phase high performance liquid chromatography(RP-HPLC), were used to isolate the ACE inhibition peptides. The amino acid sequences of the peptides were identified as Ile-Asn-Asp, Val-Glu-Pro-Gly and Leu-Ala-Asp-Glu-Phe. The IC_(50) values of the purified peptides for ACE inhibition activity were 34.72 μmol L^(-1), 20.55 μmol L^(-1) and 22.77 μmol L^(-1), respectively. These results suggested that S. nudus proteins contain specific peptides that can be released by enzymatic hydrolysis. This study may provide an experimental basis for further systematic research, rational development and clinical utilization of sandworm resources.

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.

Multifunctional interlayer with simultaneously capturing and catalytically converting polysulfides for boosting safety and performance of lithium-sulfur batteries at high-low temperatures

Lithium-sulfur(Li-S) batteries as extremely promising high-density energy storage devices have attracted extensive concern. However, practical applications of Li-S batteries are severely restricted by not only intrinsic polysulfides shuttle resulting from their concentration gradient diffusion and sluggish conversion kinetics but also serious safety issue caused by thermolabile and combustible polymer separators.Herein, it is presented for the first time that a robust and multifunctional separator with urchin-like Co-doped Fe OOH microspheres and multiwalled carbon nanotubes(MWCNTs) as an interlayer simultaneously achieves to suppress polysulfides shuttle as well as improves thermotolerance and nonflammability of commercial PP separator. Accordingly, Li-S batteries with modified separator exhibit remarkable performance in a wide range temperatures of-25–100 ℃. Typically, under 25 ℃, ultrahigh initial capacities of 1441 and 827.29 m A h g-1 at 1 C and 2 C are delivered, and remained capacities of 936 and 663.18 mA h g-1 can be obtained after 500 cycles, respectively. At 0.1 C, the S utilization can reach up to 97%. Significantly, at 1 C, the batteries also deliver an excellent performance with remained capacities of high to862.3, 608.4 and 420.6 m A h g-1 after 100, 300 and 450 cycles under 75, 0 and-25 ℃, respectively. This work provides a new insight for developing stable and safe high-performance Li-S batteries.