Dual assistance of surfactants in glycerol organosolv pretreatment and enzymatic hydrolysis of lignocellulosic biomass for bioethanol production.

This study investigated an innovative strategy of incorporating surfactants into alkaline-catalyzed glycerol pretreatment and enzymatic hydrolysis to improve lignocellulosic biomass (LCB) conversion efficiency. Results revealed that adding 40 mg/g PEG 4000 to the pretreatment at 195 °C obtained the highest glucose yield (84.6%). This yield was comparable to that achieved without surfactants at a higher temperature (240 °C), indicating a reduction of 18.8% in the required heat input. Subsequently, Triton X-100 addition during enzymatic hydrolysis of PEG 4000-assisted pretreated substrate increased glucose yields to 92.1% at 6 FPU/g enzyme loading. High-solid fed-batch semi-simultaneous saccharification and co-fermentation using this dual surfactant strategy gave 56.4 g/L ethanol and a positive net energy gain of 1.4 MJ/kg. Significantly, dual assistance with surfactants rendered 56.3% enzyme cost savings compared to controls without surfactants. Therefore, the proposed surfactant dual-assisted promising approach opens the gateway to economically viable enzyme-mediated LCB biorefinery.

Surfactants facilitated glycerol organosolv pretreatment of lignocellulosic biomass by structural modification for co-production of fermentable sugars and highly reactive lignin.

This study reported that surfactants could facilitate the organosolv pretreatment of lignocellulosic biomass (LCB) to produce fermentable sugars and highly active lignin. Under the optimized conditions, the surfactant-assisted glycerol organosolv (saGO) pretreatment achieved 80.7% delignification with a retention of 93.4% cellulose and 83.0% hemicellulose. The saGO pretreated substrate exhibited an excellent enzymatic hydrolyzability, achieving 93% of glucose yield from the enzymatic hydrolysis at 48 h. Structural analysis showed that the saGO lignin contained rich ß-O-4 bondings with less repolymerization and lower phenolic hydroxyl groups, thus forming highly reactive lignin fragments. The analysis evidenced that the surfactant graft the lignin by structural modification, which was responsible for the excellent substrate hydrolyzability. The co-production of fermentable sugars and organosolv lignin almost recovered a gross energy (87.2%) from LCB. Overall, the saGO pretreatment holds a lot of promise for launching a novel pathway towards lignocellulosic fractionation and lignin valorization.

Sustainable lignocellulose fractionation by integrating p-toluenesulfonic acid/pentanol pretreatment with mannitol for efficient production of glucose, native-like lignin, and furfural.

A new cutting-edge lignocellulose fractionation technology for the co-production of glucose, native-like lignin, and furfural was introduced using mannitol (MT)-assisted p-toluenesulfonic acid/pentanol pretreatment, as an eco-friendly process. The addition of optimized 5% MT in pretreatment enhanced the delignification rate by 29% and enlarged the surface area and biomass porosity by 1.07-1.80 folds. This increased the glucose yield by 45% (from 65.34 to 94.54%) after enzymatic hydrolysis relative to those without MT. The extracted lignin in the organic phase of pretreatment exhibited ß-O-4 bonds (61.54/100 Ar) properties of native cellulosic enzyme lignin. Lignin characterization and molecular docking analyses revealed that the hydroxyl tails of MT were incorporated with lignin and formed etherified lignin, which preserved high lignin integrity. The solubilized hemicellulose (96%) in the liquid phase of pretreatment was converted into furfural with a yield of 83.99%. The MT-assisted pretreatment could contribute to a waste-free biorefinery pathway toward a circular bioeconomy.

Polypharmacology of ambroxol in the treatment of COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still underway. Due to the growing development of severe symptoms, it is necessary to promote effective therapies. Ambroxol [2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine] has long been used as one of the over-the-counter mucolytic agents to treat various respiratory diseases. Therefore, we focused on the mechanism of action of ambroxol in COVID-19 treatment. In vitro and in silico screening revealed that ambroxol may impede cell entry of SARS-CoV-2 by binding to neuropilin-1. Ambroxol could also interact with multiple inflammatory factors and signaling pathways, especially nuclear factor kappa B (NF-κB), to interfere cytokines cascade activated by SARS-CoV-2 internalization. Furthermore, multipathways and proteins, such as the cell cycle and matrix metalloproteinases (MMPs), were identified as significant ambroxol-targeting pathways or molecules in PBMC and lung of severe COVID-19 patients by bioinformatics analysis. Collectively, these results suggested that ambroxol may serve as a promising therapeutic candidate for the treatment of severe SARS-CoV-2 infection.

Advances in organosolv modified components occurring during the organosolv pretreatment of lignocellulosic biomass.

The valorization of organosolv pretreatment (OP) is a required approach to the industrialization of the current enzyme-mediated lignocellulosic biorefinery. Recent literature has demonstrated that the solvolysis happening in the OP can modify the soluble components into value-added active compounds, namely organosolv modified lignin (OML) and organosolv modified sugars (OMSs), in addition to protecting them against excessive degradation. Among them, the OML is coincidental with the "lignin-first" strategy that should render a highly reactive lignin enriched with ß-O-4 linkages and less condensed structure by organosolv grafting, which is desirable for the transformation into phenolic compounds. The OMSs are valuable glycosidic compounds mainly synthesized by trans-glycosylation, which can find potential applications in cosmetics, foods, and healthcare. Therefore, a state-of-the-art OP holds a big promise of lowering the process cost by the valorization of these active compounds. Recent advances in organosolv modified components are reviewed, and perspectives are made for addressing future challenges.

Positive role of non-catalytic proteins on mitigating inhibitory effects of lignin and enhancing cellulase activity in enzymatic hydrolysis: Application, mechanism, and prospective.

Fermentable sugar production from lignocellulosic biomass has received considerable attention and has been dramatic progress recently. However, due to low enzymatic hydrolysis (EH) yields and rates, a high dosage of the costly enzyme is required, which is a bottleneck for commercial applications. Over the last decades, various strategies have been developed to reduce cellulase enzyme costs. The progress of the non-catalytic additive proteins in mitigating inhibition in EH is discussed in detail in this review. The low efficiency of EH is mostly due to soluble lignin compounds, insoluble lignin, and harsh thermal and mechanical conditions of the EH process. Adding non-catalytic proteins into the EH is considered a simple and efficient approach to boost hydrolysis yield. This review discussed the multiple mechanical steps involved in the EH process. The effect of physicochemical properties of modified lignin on EH and its interaction with cellulase and cellulose are identified and discussed, which include hydrogen bonding, hydrophobic, electrostatic, and cation-π interactions, as well as physical barriers. Moreover, the effects of different conditions of EH that lead to cellulase deactivation by thermal and mechanical mechanisms are also explained. Finally, recent advances in the development, potential mechanisms, and economic feasibility of non-catalytic proteins on EH are evaluated and perspectives are presented.

One-step lignocellulose fractionation using acid/pentanol pretreatment for enhanced fermentable sugar and reactive lignin production with efficient pentanol retrievability.

To valorize whole lignocellulosic biomass, this study proposed a biphasic solvent system using dilute acid (DA)/pentanol pretreatment. Effects of the key factors, i.e., temperature and pentanol concentration, on aspen were evaluated. Under identified optimal pretreatment conditions (160 °C, 60% pentanol), 85% and 91% of lignin and hemicellulose were solubilized in separate organic and liquid phases, respectively, while 91.1% of cellulose was retained in solid fraction. Enzymatic digestibility efficiency of pretreated cellulose was âˆ¼ 6.4-times higher than that of untreated biomass. Notably, excellent pentanol recovery rates were obtained after four-times recycling (84%) with great cellulose digestibility (81%) and delignification (71%) performance. The recovered lignin contained low levels of contaminated sugars (<1%), while it could stabilize and protect high amounts of ß-O-4 bonds. Besides, high phenolic OH content was found in lignin, which could be utilized for lignin-based biomaterials. Therefore, DA/pentanol pretreatment is an innovative promising technology for lignocellulosic valorization towards biorefinery.

Glycerol organosolv pretreatment can unlock lignocellulosic biomass for production of fermentable sugars: Present situation and challenges.

The complex structure of lignocellulosic biomass forms the recalcitrance to prevent the embedded holo-cellulosic sugars from undergoing the biodegradation. Therefore, a pretreatment is often required for an efficient enzymatic lignocellulosic hydrolysis. Recently, glycerol organosolv (GO) pretreatment is revealed potent in selective deconstruction of various lignocellulosic biomass and effective improvement of enzymatic hydrolysis. Evidently, the GO pretreatment is capable to modify the structure of dissolved components by glycerolysis, i.e., by trans-glycosylation onto glyceryl glycosides and by hydroxylation grafting onto glyceryl lignin. Such modifications tend to protect these main components against excessive degradation, which can be mainly responsible for the obviously less fermentation inhibitors arising in the GO pretreatment. This pretreatment can provide opportunities for valorization of emerging lignocellulosic biorefinery with production of value-added biochemicals. Recent advances in GO pretreatment of lignocellulosic biomass followed by enzymatic hydrolysis are reviewed, and perspectives are made for addressing remaining challenges.

Efficiency enhancement of a new cellulase cocktail at low enzyme loading for high solid digestion of alkali catalyzed atmospheric glycerol organosolvent pre-treated sugarcane bagasse.

The acquisition during biomass saccharification of elevated levels of fermentable sugars with lower cellulase concentration is central to ensuring an economically viable and industrially relevant hydrolytic process. Thus, using a new cellulase preparation (LT4) at low cellulase loading (2 mg protein/g dried substrate), this study assessed the possible boosting effect of integrating accessory enzymes and additives on high-solids hydrolysis of sugarcane bagasse via fed-batch feeding. Hydrolysis which commenced with initial 8% solids loading and subsequent substrate feeding of 4% solids at 6 h, 18 h, and 24 h respectively, proved optimal for the 20% high-solids saccharification producing 158 g/L total sugars and 83% glucose yield after 72 h with the combined optimized additives and accessory enzymes. The results obtained indicate that the integration of accessory enzymes and additives offers a benignant approach to minimizing the enzyme load and cost of high solids saccharification of lignocellulosic heteropolymers while also boosting enzyme hydrolytic performance.

Thermostable Cellulases / Xylanases From Thermophilic and Hyperthermophilic Microorganisms: Current Perspective.

The bioconversion of lignocellulose into monosaccharides is critical for ensuring the continual manufacturing of biofuels and value-added bioproducts. Enzymatic degradation, which has a high yield, low energy consumption, and enhanced selectivity, could be the most efficient and environmentally friendly technique for converting complex lignocellulose polymers to fermentable monosaccharides, and it is expected to make cellulases and xylanases the most demanded industrial enzymes. The widespread nature of thermophilic microorganisms allows them to proliferate on a variety of substrates and release substantial quantities of cellulases and xylanases, which makes them a great source of thermostable enzymes. The most significant breakthrough of lignocellulolytic enzymes lies in lignocellulose-deconstruction by enzymatic depolymerization of holocellulose into simple monosaccharides. However, commercially valuable thermostable cellulases and xylanases are challenging to produce in high enough quantities. Thus, the present review aims at giving an overview of the most recent thermostable cellulases and xylanases isolated from thermophilic and hyperthermophilic microbes. The emphasis is on recent advancements in manufacturing these enzymes in other mesophilic host and enhancement of catalytic activity as well as thermostability of thermophilic cellulases and xylanases, using genetic engineering as a promising and efficient technology for its economic production. Additionally, the biotechnological applications of thermostable cellulases and xylanases of thermophiles were also discussed.

Temporal Causal Inference with Time Lag.

Accurate causal inference among time series helps to better understand the interactive scheme behind the temporal variables. For time series analysis, an unavoidable issue is the existence of time lag among different temporal variables. That is, past evidence would take some time to cause a future effect instead of an immediate response. To model this process, existing approaches commonly adopt a prefixed time window to define the lag. However, in many real-world applications, this parameter may vary among different time series, and it is hard to be predefined with a fixed value. In this letter, we propose to learn the causal relations as well as the lag among different time series simultaneously from data. Specifically, we develop a probabilistic decomposed slab-and-spike (DSS) model to perform the inference by applying a pair of decomposed spike-and-slab variables for the model coefficients, where the first variable is used to estimate the causal relationship and the second one captures the lag information among different temporal variables. For parameter inference, we propose an efficient expectation propagation (EP) algorithm to solve the DSS model. Experimental results conducted on both synthetic and real-world problems demonstrate the effectiveness of the proposed method. The revealed time lag can be well validated by the domain knowledge within the real-world applications.

A Fast and Efficient Algorithm for Mining Top-k Nodes in Complex Networks.

One of the key problems in social network analysis is influence maximization, which has great significance both in theory and practical applications. Given a complex network and a positive integer k, and asks the k nodes to trigger the largest expected number of the remaining nodes. Many mature algorithms are mainly divided into propagation-based algorithms and topology- based algorithms. The propagation-based algorithms are based on optimization of influence spread process, so the influence spread of them significantly outperforms the topology-based algorithms. But these algorithms still takes days to complete on large networks. Contrary to propagation based algorithms, the topology-based algorithms are based on intuitive parameter statistics and static topology structure properties. Their running time are extremely short but the results of influence spread are unstable. In this paper, we propose a novel topology-based algorithm based on local index rank (LIR). The influence spread of our algorithm is close to the propagation-based algorithm and sometimes over them. Moreover, the running time of our algorithm is millions of times shorter than that of propagation-based algorithms. Our experimental results show that our algorithm has a good and stable performance in IC and LT model.

WITHDRAWN: Resveratrol increases microRNA-130a expression to promote angiogenesis and improve heart functions in mice after myocardial infarction.

This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Antisense expression of PKCalpha improved sensitivity of SGC7901/VCR cells to doxorubicin.

AIM: To explore whether antisense blocking of protein kinase C alpha (PKCalpha) would reverse multi-drug resistance (MDR) in the vincristine (VCR)-resistant human gastric cancer cell line SGC7901/VCR. METHODS: SGC7901/VCR cells expressing antisense PKCalpha, SGC7901/VCR/aPKC, were established by transfection with a recombinant plasmid reversely inserted with PKCalpha cDNA. Empty vector (PCI-neo)-transfected cell clones, SGC7901/VCR/neo, served as the control. Western blot method was used to detect PKCalpha content in SGC7901, SGC7901/VCR, SGC7901/VCR/neo and SGC7901/VCR/aPKC cells, using PKCalpha-specific antibody. The sensitivity of SGC7901, SGC7901/VCR, SGC7901/VCR/neo and SGC7901/VCR/aPKC cells to doxorubicin (DOX) in vitro was determined by MTT assay. The uptake of DOX in these cells was detected with fluorescence spectrophotometer. RESULTS: Western blot analysis showed that the PKCalpha protein level was about 8.7-fold higher in SGC7901/VCR cells than that in SGC7901 cells, whereas the protein expression of PKCalpha was reduced by 78% in SGC7901/VCR/aPKC cells when compared with the SGC7901/VCR cells. SGC7901/VCR/aPKC cells had a 4.2-fold increase in DOX cytotoxicity, accompanied by a 1.7-fold increase of DOX accumulation in comparison with SGC7901/VCR cells. CONCLUSION: PKCalpha positively regulates MDR in SGC7901 cells, and inhibition of PKCalpha can partially attenuate MDR in human gastric cancer cells.

Heat shock protein 20 interacting with phosphorylated Akt reduces doxorubicin-triggered oxidative stress and cardiotoxicity.

Doxorubicin (DOX) is a widely used antitumor drug, but its application is limited because of its cardiotoxic side effects. Heat shock protein (Hsp)20 has been recently shown to protect cardiomyocytes against apoptosis, induced by ischemia/reperfusion injury or by prolonged beta-agonist stimulation. However, it is not clear whether Hsp20 would exert similar protective effects against DOX-induced cardiac injury. Actually, DOX treatment was associated with downregulation of Hsp20 in the heart. To elucidate the role of Hsp20 in DOX-triggered cardiac toxicity, Hsp20 was first overexpressed ex vivo by adenovirus-mediated gene delivery. Increased Hsp20 levels conferred higher resistance to DOX-induced cell death, compared to green fluorescent protein control. Furthermore, cardiac-specific overexpression of Hsp20 in vivo significantly ameliorated acute DOX-triggered cardiomyocyte apoptosis and animal mortality. Hsp20 transgenic mice also showed improved cardiac function and prolonged survival after chronic administration of DOX. The mechanisms underlying these beneficial effects were associated with preserved Akt phosphorylation/activity and attenuation of DOX-induced oxidative stress. Coimmunoprecipitation studies revealed an interaction between Hsp20 and phosphorylated Akt. Accordingly, BAD phosphorylation was preserved, and cleaved caspase-3 was decreased in DOX-treated Hsp20 transgenic hearts, consistent with the antiapoptotic effects of Hsp20. Parallel ex vivo experiments showed that either infection with a dominant-negative Akt adenovirus or preincubation of cardiomyocytes with the phosphatidylinositol 3-kinase inhibitors significantly attenuated the protective effects of Hsp20. Taken together, our findings indicate that overexpression of Hsp20 inhibits DOX-triggered cardiac injury, and these beneficial effects appear to be dependent on Akt activation. Thus, Hsp20 may constitute a new therapeutic target in ameliorating the cardiotoxic effects of DOX treatment in cancer patients.

A human polymorphism of protein phosphatase-1 inhibitor-1 is associated with attenuated contractile response of cardiomyocytes to beta-adrenergic stimulation.

Aberrant beta-adrenergic signaling and depressed calcium homeostasis, associated with an imbalance of protein kinase A and phosphatase-1 activities, are hallmarks of heart failure. Phosphatase-1 is restrained by its endogenous inhibitor, protein phosphatase inhibitor-1 (PPI-1). We assessed 352 normal subjects, along with 959 patients with heart failure and identified a polymorphism in PPI-1 (G147D) exclusively in black subjects. To determine whether the G147D variant could affect cardiac function, we infected adult cardiomyocytes with adenoviruses expressing D147 or wild-type (G147) PPI-1. Under basal conditions, there were no significant differences in fractional shortening or contraction or relaxation rates. However, the enhancement of contractile parameters after isoproterenol stimulation was significantly blunted in D147 compared with G147 and control myocytes. Similar findings were observed in calcium kinetics. The attenuated beta-agonist response was associated with decreased (50%) phosphorylation of phospholamban (PLN) at serine 16, whereas phosphorylation of troponin I and ryanodine receptor was unaltered. These findings suggest that the human G147D PPI-1 can attenuate responses of cardiomyocytes to beta-adrenergic agonists by decreasing PLN phosphorylation and therefore may contribute to deteriorated function in heart failure.

Small heat-shock protein Hsp20 attenuates beta-agonist-mediated cardiac remodeling through apoptosis signal-regulating kinase 1.

Chronic stimulation of the beta-adrenergic neurohormonal axis contributes to the progression of heart failure and mortality in animal models and human patients. In cardiomyocytes, activation of the beta-adrenergic pathway has been shown to result in transiently increased expression of a cardiac small heat-shock protein Hsp20. The present study shows that cardiac overexpression (10-fold) of Hsp20 may protect the heart against beta-agonist-induced cardiac remodeling, associated with isoproterenol (50 mug/g per day) infusion for 14 days. Hsp20 attenuated the cardiac hypertrophic response, markedly reduced interstitial fibrosis, and decreased apoptosis. Contractility was also preserved in hearts with increased Hsp20 levels. These beneficial effects were associated with attenuation of the ASK1-JNK/p38 (apoptosis signal-regulating kinase 1/c-Jun NH(2)-terminal kinase/p38) signaling cascade triggered by isoproterenol, whereas there was no difference in either extracellular signal-related kinase 1/2 or Akt activation. Parallel in vitro experiments supported the inhibitory role of Hsp20 on enforced ASK1-JNK/p38 activation in both H9c2 cells and adult rat cardiomyocytes. Immunostaining studies also demonstrated that Hsp20 colocalizes with ASK1 in cardiomyocytes. Taken together, our findings indicate that (1) beta-agonist-induced cardiac injury is associated with activation of the ASK1-JNK/p38 cascade; (2) increased expression of Hsp20 attenuates the induction of remodeling, dysfunction, and apoptosis in response to sustained beta-adrenergic stimulation; and (3) the beneficial effects of Hsp20 are at least partially attributable to inhibition of the ASK1-signaling cascade.

Alterations in vascular matrix metalloproteinase due to ageing and chronic hypertension: effects of endothelin receptor blockade.

OBJECTIVE: To determine the effects of age and dual endothelin (ET)A/ETB receptor antagonism (bosentan) on aortic matrix metalloproteinase (MMP) abundance and tissue inhibitor of metalloproteinase (TIMP) expression in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). METHODS: Male SHR and control WKY rats were randomly assigned to receive placebo or bosentan (100 mg/kg per day) for 3 months. Animals were killed under terminal anaesthesia at either 20 weeks (adult) or 17-20 months (senescent). Aortic gelatinase activity was determined by zymography, whereas MT-1 MMP and TIMP-1 expression were assessed by immunoblotting. RESULTS: In WKY rats, aortic MMP-2 but not proMMP-2 activity was 3.6-fold higher (P < 0.02) in the senescent compared with the adult group. TIMP-1 (twofold) and MT-1 MMP (3.8-fold) expression increased (P < 0.05) with age in the WKY groups. Short-term hypertension (adult SHR versus adult WKY) increased MMP-2 to 74.7 +/- 14.1 from 18.9 +/- 3.5 arbitrary units (AU) (P = 0.0012), but did not alter proMMP-2 activity. This increased further on progression to chronic hypertension (117.4 +/- 12.2 versus 74.7 +/- 14.1 AU; P < 0.02). Bosentan decreased MMP-2 (78.9 +/- 3.8 versus 117.4 +/- 12.2 AU; P = 0.014) and proMMP-2 activity (P < 0.006) in the senescent SHR group. CONCLUSION: Ageing and the development/progression of hypertension are associated with increased MMP-2 activity in the aorta, which is consistent with ongoing remodelling of the vasculature. However, the underlying mechanisms regulating MMP-2 abundance in ageing and hypertension appear to be divergent, as MT-1 MMP expression is differentially altered. Dual ETA/ETB receptor antagonism did not alter the age-dependent increase in aortic MMP activity in normotensive rats. However, bosentan decreased pro and active MMP-2 activity in senescent SHR rats, indicating that ET modulates late events in vascular remodelling in hypertension.

Dynamic changes in myocardial matrix metalloproteinase activity in mice with viral myocarditis.

BACKGROUND: Matrix metalloproteinases (MMPs) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart. The purpose of this study was to investigate the dynamic changes in myocardial MMP activity in mice with viral myocarditis (VM), the relationship between MMP activity and both cardiac function and the quantity of myocardial collagen, and the role MMPs playing in the pathological lesions of VM. METHODS: Sixty-five six-week-old male DBA/2 mice were divided into two groups. Mice in the infected group (n = 50) were inoculated intraperitoneally with 0.14 ml of Coxsackievirus B3 (CVB3, Nancy strain). Control mice (n = 15) were inoculated intraperitoneally with 0.14 ml of Eagle's medium. Eight infected mice and three control mice were sacrificed on each of days 3, 7, 10, 21 and 30 after inoculation. MMP activity was measured on an SDS-PAGE substrate gel embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate administered intraperitoneally (0.01 ml/g - 0.015 ml/g). Cardiac systolic function indices, such as peak velocity of the aorta (Vp), flow velocity integral of the aorta (Vi), ejection fraction (EF), and fractional shortening (FS) were determined by echocardiography. Histological cross sections of the hearts were stained with hematoxylin-eosin and myocardial histopathological scores were determined under an optical microscope. The amount of myocardial collagen was measured by means of hydroxyproline quantification. RESULTS: In virus-infected mice, both MMP-2 and MMP-9 activities were significantly higher than in control mice, reaching a peak on day 10 (P < 0.01). On day 10, cardiac systolic function indices (EF, FS, Vp, and Vi) were all significantly lower compared both to other stages following viral inoculation and to the control group (P < 0.05). In the acute stage, the amount of myocardial collagen in mice with VM was not significantly different from normal control mice (P > 0.05). However, the amount of myocardial collagen in infected mice at the recovery stage (on days 21 and 30) was significantly greater than those of the control mice. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores (r = 0.801, 0.821, P < 0.01) and negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi (r = -0.711, -0.755, P < 0.01). However, Vp negatively correlated with myocardial histopathological scores (r = -0.756, P < 0.01). CONCLUSIONS: In mice with VM, the activities of myocardial MMP-2 and MMP-9 increase significantly during the acute stage, and the total quantity of myocardial collagen increases by the time of recovery. These changes are associated with myocardial interstition remodeling and cardiac dysfunction. MMP activity is an important reference marker for myocardial pathological lesions and can be used to evaluate the severity of myocardial interstitial damage and cardiac dysfunction.