Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.

Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of the EGFR signaling pathway

The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.

Engineering high amylose and resistant starch in maize by CRISPR/Cas9-mediated editing of starch branching enzymes

To improve the amylose content(AC)and resistant starch content(RSC)of maize kernel starch,we employed the CRISPR/Cas9 system to create mutants of starch branching enzyme I(SBEI)and starch branching enzyme IIb(SBEIIb).A frameshift mutation in SBEI(E1,a nucleotide insertion in exon 6)led to plants with higher RSC(1.07%),lower hundred-kernel weight(HKW,24.71±0.14 g),and lower plant height(PH,218.50±9.42 cm)compared to the wild type(WT).Like the WT,E1 kernel starch had irregular,polygonal shapes with sharp edges.A frameshift mutation in SBEIIb(E2,a four-nucleotide deletion in exon 8)led to higher AC(53.48%)and higher RSC(26.93%)than that for the WT.E2 kernel starch was significantly different from the WT regarding granule morphology,chain length distribution pattern,X-ray diffraction pattern,and thermal characteristics;the starch granules were more irregular in shape and comprised typical B-type crystals.Mutating SBEI and SBEIIb(E12)had a synergistic effect on RSC,HKW,PH,starch properties,and starch biosynthesis-associated gene expression.SBEIIa,SS1,SSIIa,SSIIIa,and SSIIIb were upregulated in E12 endosperm compared to WT endosperm.This study lays the foundation for rapidly improving the starch properties of elite maize lines.

Addition of Protease Enzyme to Dog and Cat Feed and Its Influence on the Digestibility Coefficient, Immune Response, and Metabolic Biomarkers

Promoting better protein digestibility through exogenous enzymes in the diet is essential in the nutrition of companion animals, mainly for better performance and maintenance of the animals’ physiological and metabolic systems, promoting health and adequate growth. In addition, it reduces the cost of the diet by possibly reducing protein in the diet, which is the main and most expensive ingredient for dogs and cats. The objective of this study was to verify whether the addition of protease to dog and cat food can improve the protein digestibility of the food, thus facilitating greater absorption of amino acids and influencing metabolic biomarkers and immune response. To this end, two experiments were carried out to evaluate the protease from the fermentation of Aspergillus niger and Bacillus subtilis. Experiment 1 was carried out with ten male, non-castrated beagles divided into two groups of five animals: the control group (without enzyme) and the test group (with 250 g of protease/ton). The animals underwent two 45-day experimental periods, and in the second period, after a 15-day interval, the dogs in the control group became part of the treatment group (crossover model). Adding this enzyme to the dogs’ diet had no adverse effects on the animals’ health besides improving the digestibility of dry matter and crude protein consumed by the dogs. Experiment 2 was carried out with sixteen female cats of no defined breed, non-castrated, divided into four groups with four animals per group, namely: Treatment A (without enzyme), Treatment B (with protease at a dose of 100 g/ton), Treatment C (with protease at a dose of 200 g/ton) and Treatment D (with protease at a dose of 400 g/ton). The cats underwent two 30-day experimental periods, and in the second period, after a 15-day interval, the animals switched between treatments (crossover model) to increase the power of the statistical test. The enzyme consumption did not affect the felines’ metabolism and health but improved the digestibility of crude protein at doses of 200 and 400 g/ton. The results allow us to conclude that the protease used in this study can improve the digestibility of crude protein for dogs and cats.

Processing Effects on Selected Antioxidant Activities and Metabolizing Enzyme Inhibition of M. Koneigii (Curry Leaves) Extracts

Curry leaves, scientifically termed Murraya koenigii, are renowned in South Asian cuisine for their flavor enhancement and potential health benefits, including antioxidative, anti-inflammatory, and antidiabetic properties. This study aimed to evaluate the impact of thermal processing methods on curry leaves by analysing Total Phenolic Content (TPC), Total Flavonoid Content (TFC), antioxidant activity, and metabolizing enzyme inhibition. Fresh curry leaves were subjected to thermal treatments: Oven-dried at 60˚C and Air-dried at 25˚C for 2 weeks. Extracts were prepared using Ethanol and water solvents. Results indicated that Air-dried leaves exhibited significantly higher TPC (5132.65 mg GAE/100 g) and TFC (243.13 mg CE/100 g) compared to Fresh and Oven-dried leaves. Antioxidant assays show that oven-dried curry leaves at 60˚C displayed higher results in NORS, FRAP, and TEAC assays compared to Fresh and Air-dried leaves. Ethanol extracts showed better extraction of bioactive compounds than aqueous extracts. Moreover, Lipase inhibition activity was notably high, indicating potential health benefits. This study provides valuable insights into the effects of processing methods on curry leaf extracts, emphasizing the importance of solvent selection for optimal extraction of bioactive compounds.

Dietary manganese supplementation inhibits abdominal fat deposition possibly by regulating gene expression and enzyme activity involved in lipid metabolism in the abdominal fat of broilers

Excessive abdominal fat deposition seriously restricts the production efficiency of broilers.Several studies found that dietary supplemental manganese(Mn)could effectively reduce the abdominal fat deposition of broilers,but the underlying mechanisms remain unclear.The present study aimed to investigate the effect of dietary supplementation with the inorganic or organic Mn on abdominal fat deposition,and enzyme activity and gene expression involved in lipid metabolism in the abdominal fat of male or female broilers.A total of 4201-d-old AA broilers(half males and half females)were randomly allotted by body weight and gender to 1 of 6 treatments with 10 replicates cages of 7 chicks per cage in a completely randomized design involving a 3(dietary Mn addition)×2(gender)factorial arrangement.Male or female broilers were fed with the Mn-unsupplemented basal diets containing 17.52 mg Mn kg^(-1)(d 1-21)and 15.62 mg Mn kg^(-1)(d 22-42)by analysis or the basal diets supplemented with 110 mg Mn kg^(-1)(d 1-21)and 80 mg Mn kg^(-1)(d 22-42)as either the Mn sulfate or the Mn proteinate with moderate chelation strength(Mn-Prot M)for 42 d.The results showed that the interaction between dietary Mn addition and gender had no impact(P>0.05)on any of the measured parameters;abdominal fat percentage of broilers was decreased(P<0.003)by Mn addition;Mn addition increased(P<0.004)adipose triglyceride lipase(ATGL)activity,while Mn-Prot M decreased(P<0.002)the fatty acid synthase(FAS)activity in the abdominal fat of broilers compared to the control;Mn addition decreased(P<0.009)diacylglycerol acyltransferase 2(DGAT2)mRNA expression level and peroxisome proliferator-activated receptor γ(PPARγ)mRNA and protein expression levels,but up-regulated(P<0.05)the ATGL mRNA and protein expression levels in the abdominal fat of broilers.It was concluded that dietary supplementation with Mn inhibited the abdominal fat deposition of broilers possibly via decreasing the expression of PPARγand DGAT2 as well as increasing the expression and activity of ATGL in the abdominal fat of broilers,and Mn-Prot M was more effective in inhibiting the FAS acitivity.

Identification of key enzymes in lignocellulose biosynthesis from dynamic observations in maize stalks

Maize stalk lignin and cellulose contents are linked to lodging resistance,disease resistance,feed quality and ethanol conversion efficiency.After the six-leaf stage of maize(V6),these constituents are biosynthesized and accumulated under the control of related enzymes and genes.However,the key enzymes,critical MYB transcription factors,and their dynamic alterations pattern under natural field circumstances are still unknown.Hence,we selected five cultivars with significant differences in lignocellulose content and lodging resistance as testing materials,performed field experiments for two years,and investigated the dynamics of lignin and cellulose content,related enzyme concentrations,and gene expression levels in the 3^(rd) and 5^(th) internodes above the ground after V6.The results showed that lignin and cellulose content increased after V6,stabilizing during the silking stage.This study identified COMT(caffeic acid 3-Omethyltransferase),TAL(tyrosine ammonia-lyase)and PAL(phenylalanine ammonia-lyase)as the key enzymes of lignin biosynthesis,while ZmCOMT,ZmCesA10 and ZmCesA8 were identified as essential genes.ZmMYB8,ZmMYB31 and ZmMYB39 were involved in regulating the expression of genes related to lignin synthesis,with ZmMYB31 potentially acting as a key negative regulator,while ZmMYB39 and ZmMYB8 acting as positive regulators.The study also found that around 14 d after V6 was a critical stage for regulating lignocellulose synthesis in the 3^(rd) to 5^(th) basal internode.This provides a theoretical foundation for developing regulatory techniques and breeding new cultivars to enhance lodging and disease resistance as well as the utility of maize stalks.

Preparative Fractionation of Feruloyl Oligosaccharides Produced by Combinatorial Enzyme Digestion of Arabinoxylan

Pretreated wheat insoluble arabinoxylan was converted to oligosaccharides of structural variants using combinatorial enzyme approach. The digestive products were separated by preparative scale chromatographic Amberlite XAD-2 column. Fractions containing feruloyl oligosaccharides (FOS) were isolated, pooled, freeze-dried, and demonstrated to possess antimicrobial activity. The FOS suppressed cell growth of the test organism ATCC 8739 E. coli with a MIC value of 0.028% (w/v, 35˚C, 24 hr). The antimicrobial action was observed exceeding 72 hr of culture incubation. The FOS product could be a useful source of prebiotics or preservatives. The present results further confirm the science and application of the concept of combinatorial enzyme technique.

Responses of soil stoichiometry and soil enzyme activities in the different distance around opencast coal mine of the Hulun Buir Grassland of China

The objectives of this study were to explore the changes in soil stoichiometry and enzyme activities at different distances from an opencast coal mine in the Hulun Buir Grassland of China. Four transects were established on north and east sides of the opencast coal mining area, and samples were collected at 50 m, 550 m, and 1550 m from the pit on each transect. Control samples were collected from a grassland station 8 km from the opencast coal mining area that was not disturbed by mining. Four replicate soil samples were collected at each point on the four transects. Soil physicochemical properties and enzyme activities were determined, and correlations between soil properties and stoichiometric ratios and enzyme activities were explored using redundancy analysis. The increase in distance from mining did not significantly affect soil properties, although soil urease activity was significantly lower than that of the control area. Soil properties 1550 m from the mine pit were similar to those at the grassland control. In addition, soil total nitrogen had the greatest effect on soil stoichiometry, and soil total potassium had the greatest effect on soil enzyme activities. Coal dust from opencast mining might be the main factor affecting soil stoichiometry and enzyme activities. The results of this study provide direction for the next step in studying the influence of mining areas on soil properties and processes.

Responses of soil enzyme and microbial community under co-loading of different microplastics and sulfamethoxazole

Polyamide/polyethylene(PA/PE)microplastics were injected into soil containing sulfamethoxazole(SMX)to investigate their combined effects on SMX removal,soil enzyme activity,and microbial communities.The results show that both PA and PE transiently increase SMX removal and inhibite the stimulation of microbial species diversity by SMX.The effect of PE is more significant.Meanwhile,PE combined with SMX increases the relative abundances of Actinobacteria and Pseudomonas,while PA combined with SMX decreases the relative abundances of Nocardioides and Streptomyces.In addition,PA/PE combined with SMX can increase dehydrogenase,urease,ammonia monooxygenase,and nitrate reductase activities in the soil while inhibiting the activity of laccase.Compared with PA combined with SMX,the activities of dehydrogenase,urease,ammonia monooxygenase,and laccase of PE combined with SMX increase by 9.82%,10.41%,8.07%,and 5.47%,while the activities of nitrate reductase and neutral phosphatase decrease by 1.47%and 6.78%.

The Integration of Water and Fertilizer Regulated Soil Nutrients and Enzyme Activities of Greenhouse Tomato (Solanum lycopersicum) by Moistube Irrigation

Moistube irrigation was driven by the gradient of water potential inside and outside the pipe wall,which has the advantages of continuous irrigation during the crop growth period.However,the response mechanism of soil nutrients and enzyme activities of greenhouse tomatoes under the integration of water and fertilizer by moistube irrigation is still unclear.In order to explore the changes in soil nutrients and enzyme activities of greenhouse tomatoes regulated by irrigation and fertilization in moistube irrigation greenhouse,a completely randomized experimental design was conducted to explore the effects of different irrigation amounts(I,controlling the work-ing pressure head of moistube to achieve different irrigation amount gradients,capillary working pressure was 1(I1),2(I2),3(I3)m)and fertilization amounts(F,single fertilization amount was 100(F1),200(F2),300(F3)kg/hm2)on soil nutrients,enzyme activities and yield of greenhouse tomato.It was found that with the increase of I,the total organic carbon content(TOC),soilβ-glucosidase(BG),leucine amino peptidase(LAP),N-acetylglucosaminidase(NAG),and alkaline phosphatase(AP)activities enzyme of greenhouse tomato soil increasedfirst and then decreased.When the I increased from I1 to I3,the soil total nitrogen(TN)decreased by 5.07%and 4.91%,respectively,and the soil total phosphorus(TP)by 4.37%and 4.22%,respectively.With the increase of fertilizer amounts,the TOC of tomato soil increasedfirst and then decreased,the activities of BG,LAP,NAG and AP in soil increasedfirst and then decreased,and the contents of TN and TP in soil decreased by 4.79%and 4.68%,12.32%and 10.47%,respectively.The yield of tomatoes treated with I2 was significantly higher than that of I1 and I3 by about 13.99%and 1.29%,respectively.The tomato yield of F2 treatment was significantly higher than that of F1 and F3 treatments by about 22.57%and 1.72%,respectively.Based on the analysis of stoichiometry,it was found that soil carbon was more scarcity than nitrogen in greenhouse tomatoes under the integration of water and fertilizer by moistube irrigation.Soil carbon,nitrogen,phosphorus,enzyme activity and their respective stoichiometry showed a quadratic curve relationship with yield.Therefore,I2F2 treat-ment of greenhouse tomatoes can not only reduce soil carbon and nitrogen limitations but also improve soil enzyme activity and achieve multiple goals of increasing greenhouse tomato yield,and saving water and fertilizer.This conclusion contributes to a more reasonable irrigation and fertilization of tomatoes in moistube irrigation greenhouse and soil nutrient management of facility agriculture through empirical proofs.

Response of Bacterial Community and Enzyme Activity of Greenhouse Tomato under Different Irrigation Systems

The micro-sprinkler irrigation mulched(MSM)has been suggested as a novel water-saving approach in con-trolled environment agriculture.However,the effects of microbial community structure and enzyme activity in the rhizosphere soil on crop growth under MSM remain unclear.This study conducted a randomized experimen-tal design using greenhouse tomatoes to investigate changes in bacterial community structure and enzyme activity in rhizosphere soil under different irrigation frequencies(F)and amounts(I)of MSM.Thefindings revealed that with the increase of F or I,The total count of soil bacteria in tomatoesfirst rose and then fell in terms of Opera-tional Taxonomic Units(OTUs)classification.Compared to other F,the most abundance of nitrogen and phos-phorus metabolism genes and enzyme activities were observed with a 5-day F.Moreover,the diversity of soil bacterial community structure initially rose before eventually declining with the increase of the I.Applying 1.00 Epan(cumulative evaporation of a 20 cm standard pan)under MSM helped boost the abundance of nitrogen and phosphorus metabolism functional genes in soil bacteria,ensuring higher enzyme activities related to nitro-gen,carbon,and phosphorus metabolism in the rhizosphere soil of tomatoes.Tomatoes’yield initially rose before eventually declining with the increase in F or I,whereas I had a more significant effect on yield.A 1.00%increase in I yielded a minimum of 39.24%increase in tomato yield.The study showed a positive correlation between soil bacterial community,soil enzyme activity,and greenhouse tomato yield under MSM.Considering the results comprehensively,the combined irrigation mode of F of 5 d and I of 1.00 Epan was recommended for greenhouse tomatoes under MSM.This conclusion provides theoretical support for water-saving practices and yield improve-ment in facility agriculture,especially tomato cultivation.

Conjugated microporous polymers-scaffolded enzyme cascade systems with enhanced catalytic activity

Enhancing catalytic activity of multi-enzyme in vitro through substrate channeling effect is promis-ing yet challenging.Herein,conjugated microporous polymers(CMPs)-scaffolded integrated en-zyme cascade systems(I-ECSs)are constructed through co-entrapping glucose oxidase(GOx)and horseradish peroxidase(HRP),in which hydrogen peroxide(H_(2)O_(2)) is the intermediate product.The interplay of low-resistance mass transfer pathway and appropriate pore wall-H_(2)O_(2) interactions facilitates the directed transfer of H_(2)O_(2),resulting in 2.4-fold and 5.0-fold elevation in catalytic activ-ity compared to free ECSs and separated ECSs,respectively.The substrate channeling effect could be regulated by altering the mass ratio of GOx to HRP.Besides,I-ECSs demonstrate excellent stabili-ties in harsh environments and multiple recycling.

The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

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.

Bacterial communities and enzyme activities during litter decomposition of Elymus nutans leaf on the Qinghai-Tibet Plateau

The dominant plant litter plays a crucial role in carbon(C)and nutrients cycling as well as ecosystem functions maintenance on the Qinghai-Tibet Plateau(QTP).The impact of litter decomposition of dominant plants on edaphic parameters and grassland productivity has been extensively studied,while its decomposition processes and relevant mechanisms in this area remain poorly understood.We conducted a three-year litter decomposition experiment in the Gansu Gannan Grassland Ecosystem National Observation and Research Station,an alpine meadow ecosystem on the QTP,to investigate changes in litter enzyme activities and bacterial and fungal communities,and clarify how these critical factors regulated the decomposition of dominant plant Elymus nutans(E.nutans)litter.The results showed that cellulose and hemicellulose,which accounted for 95%of the initial lignocellulose content,were the main components in E.nutans litter decomposition.The litter enzyme activities ofβ-1,4-glucosidase(BG),β-1,4-xylosidase(BX),andβ-D-cellobiosidase(CBH)decreased with decomposition while acid phosphatase,leucine aminopeptidase,and phenol oxidase increased with decomposition.We found that both litter bacterial and fungal communities changed significantly with decomposition.Furthermore,bacterial communities shifted from copiotrophic-dominated to oligotrophic-dominated in the late stage of litter decomposition.Partial least squares path model revealed that the decomposition of E.nutans litter was mainly driven by bacterial communities and their secreted enzymes.Bacteroidota and Proteobacteria were important producers of enzymes BG,BX,and CBH,and their relative abundances were tightly positively related to the content of cellulose and hemicellulose,indicating that Bacteroidota and Proteobacteria are the main bacterial taxa of the decomposition of E.nutans litter.In conclusion,this study demonstrates that bacterial communities are the main driving forces behind the decomposition of E.nutans litter,highlighting the vital roles of bacterial communities in affecting the ecosystem functions of the QTP by regulating dominant plant litter decomposition.

The Effect of Soil Enzymes and Polysaccharides Secreted by the Roots of Salvia miltiorrhiza Bunge under Drought,High Temperature,and Nitrogen and Phosphorus Deficits

Root exudates serve as crucial mediators for information exchange between plants and soil,and are an important evolutionary mechanism for plants’adaptation to environmental changes.In this study,15 different abiotic stress models were established using various stress factors,including drought(D),high temperature(T),nitrogen deficiency(N),phosphorus deficiency(P),and their combinations.We investigated their effects on the seedling growth of Salvia miltiorrhiza Bunge and the activities of Solid-Urease(S-UE),Solid-Nitrite Reductase(S-NiR),Solid-Nitrate Reductase(S-NR),Solid-Phosphotransferase(S-PT),and Solid-Catalase(S-CAT),as well as the contents of polysaccharides in the culture medium.The results showed that the growth of S.miltiorrhiza was inhibited under 15 stress conditions.Among them,13 stress conditions increased the root-shoot ratio.These 15 stress conditions significantly reduced the activity of S-NR,two combinations significantly improved the activity of S-NIR,they were synergistic stresses of high temperature and nitrogen deficiency(TN),and synergistic stresses of drought and nitrogen deficiency(DN)(p<0.05).The activity of S-UE was significantly improved under N,D,T,synergistic stresses of drought and high temperature(DT),DN,synergistic stresses of drought and phosphorus deficiency(DP),and synergistic stresses of high temperature,nitrogen,and phosphorus deficiency(TNP)stress conditions(p<0.05).Most stress combinations reduced the activity of S-PT,but D and T significantly improved it.(p<0.05).The N,DN,and TN stress conditions significantly reduced S-CAT activity.The P,DT,and synergistic stresses of drought,high temperature,and phosphorus deficiency(DTP)significantly decreased the total polysaccharide content of the soil(p<0.05).The research suggested that abiotic stress hindered the growth of S.miltiorrhiza and altered the behavior of root secretion.Roots regulated the secretion of several substances in response to various abiotic stresses,including soil nitrogen cycle enzymes,phosphorus transport-related enzymes,and antioxidant enzymes.In conclusion,plants regulate the utilization of rhizosphere substances in response to abiotic stresses by modulating the exudation of soil enzymes and polysaccharides by the root system.At the same time,soil carbon sequestration was affected by the adverse environment,which restricted the input of organic matter into the soil.

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearing loss(ISSNHL)risk and their potential prognostic effects.Methods:The study group consisted of 70 patients and the control group consisted of 50 patients.Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction.Age,sex,affected side,tinnitus,and vertiginous symptom status,number of days between symptom onset and hospital admission,pure tone audiometry results at admission and after treatment were included in the study.Data were compared statistically.Results:The D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group(p=0.032).II genotype was associated with a reduced risk of ISSNHL(p=0.036).The amount of hearing loss was significantly higher in patients with the TT genotype(p=0.027)and T allele of the IL-10 GP(p=0.035)than in the patients without this allele.Severe hearing loss was a poor prognostic factor(p=0.008).Conclusions:The D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology.Due to the association of this allele with occlusive vascular pathologies,ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.