Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway.

OBJECTIVES: To explore the anti-inflammatory effect and the potential mechanism of dexmedetomidine in ARDS/ALI. MATERIALS AND METHODS: C57BL/6 mice and EL-4 cells were used in this research. The ALI model was established by CLP. The level of inflammatory cytokines in the lung and blood, the severity of lung injury, the expression of Foxp3, and the proportion of Tregs were detected before and after dexmedetomidine treatment. The expression of the AMPK/SIRT1 after dexmedetomidine treatment was detected in vivo and in vitro. After blocking the AMPK/SIRT1 pathway or depleting Tregs in vivo, the level of the inflammatory response, tissue injury, and Tregs differentiation were detected again to clarify the effect of dexmedetomidine. RESULTS: Dexmedetomidine significantly reduced systemic inflammation and lung injury in CLP mice. Dexmedetomidine enhanced the Foxp3 expression in the lungs and the frequency of Tregs in the spleen. Dexmedetomidine up-regulated the protein expression of p-AMPK and SIRT1 in lungs and EL-4 cells and facilitated the differentiation of naïve CD4+ T cells into Tregs in vitro. Meanwhile, DEX also increased the expression of Helios in Treg cells. CONCLUSIONS: DEX could improve ARDS/ALI by facilitating the differentiation of Tregs from naïve CD4+ T cells via activating the AMPK/SIRT1 pathway.

Sequencing on an imported case in China of COVID-19 Delta variant emerging from India in a cargo ship in Zhoushan, China.

A cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was found in a cargo ship under repair in Zhoushan, China. Twelve of 20 crew members were identified as SARS-CoV-2 positive. We analyzed four sequences and identified them all in the Delta branch emerging from India with 7-8 amino acid mutation sites in the spike protein.

Potential Presymptomatic Transmission of SARS-CoV-2, Zhejiang Province, China, 2020.

We report a 2-family cluster of persons infected with severe acute respiratory syndrome coronavirus 2 in the city of Zhoushan, Zhejiang Province, China, during January 2020. The infections resulted from contact with an infected but potentially presymptomatic traveler from the city of Wuhan in Hubei Province.

Detection of Novel Coronavirus by RT-PCR in Stool Specimen from Asymptomatic Child, China.

We report an asymptomatic child who was positive for a coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.

Molecular evolution of GII.P17-GII.17 norovirus associated with sporadic acute gastroenteritis cases during 2013-2018 in Zhoushan Islands, China.

In this study, we investigated the molecular characteristics and spatio-temporal dynamics of GII.P17-GII.17 norovirus in Zhoushan Islands during 2013-2018. We collected 1849 samples from sporadic acute gastroenteritis patients between January 2013 and August 2018 in Zhoushan Islands, China. Among the 1849 samples, 134 (7.24%) samples were positive for human norovirus (HuNoV). The complete sequence of GII.17 VP1 gene was amplified from 31 HuNoV-positive samples and sequenced. A phylogenetic tree was constructed based on the full-length sequence of the VP1 gene. Phylogenetic analysis revealed that the GII.17 genotype detected during 2014-2018 belongs to the new GII.17 Kawasaki variant. Divergence analysis revealed that the time of the most recent common ancestor (TMRCA) of GII.17 in Zhoushan Islands was estimated to be between 1997 and 1998. The evolutionary rate of the VP1 gene of the GII.17 genotype norovirus was 1.14 × 10-3 (95% HPD: 0.62-1.73 × 10-3) nucleotide substitutions/site/year. The spatio-temporal diffusion analysis of the GII.17 genotype identified Hong Kong as the epicenter for GII.17 dissemination. The VP1 gene sequence of Zhoushan Island isolates correlated with that of Hong Kong and Japan isolates.

In vivo HMRS and lipidomic profiling reveals comprehensive changes of hippocampal metabolism during aging in mice.

Aging is characterized by various cellular changes in the brain. Hippocampus is important for systemic aging and lifespan control. There is still a lack of comprehensive overview of metabolic changes in hippocampus during aging. In this study, we first created an accelerated brain aging mice model through the chronic administration of d-galactose. We then performed a multiplatform metabolomic profiling of mice hippocampus using the combination of in vivo 9.4 T HMRS and in vitro LC-MS/MS based lipidomics. We found N-acetylaspartic acid (NAA), gama-aminobutyric acid (GABA), glutamate/glutamine, taurine, choline, sphingolipids (SMs), phosphatidylethanolamines (PEs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs) and phosphatidylserines (PSs), all of them decreasing with the aging process in mice hippocampus. The changes of sphingolipids and phospholipids were not limited to one single class or molecular species. In contrast, we found the significant accumulation of lactate, myoinositol and phosphatidylcholines (PCs) along with aging in hippocampus. SM (d18:1/20:2), PE (36:2), PG (34:1), PI (36:4), PS (18:0/20:4) and PC (36:0) have the most significant changes along with aging. Network analysis revealed the striking loss of biochemical connectivity and interactions between hippocampal metabolites with aging. The correlation pattern between metabolites in hippocampus could function as biomarkers for aging or diagnosis of aging-related diseases.

Performance of coralline hydroxyapatite in sinus floor augmentation: a retrospective study.

OBJECTIVE: The purpose of this study is to retrospectively explore the utilization of coralline hydroxyapatite in maxillary sinus augmentation. METHOD: One hundred and eighteen cases of sinus lift with coralline hydroxyapatite (CHA) were included in this study. In detail, simultaneous implantation was conducted in 78 patients (174 implants) and delayed implantation was done in 40 cases (82 implants) around 6 months after bone transplantation. The clinical features and X-ray radiographs after operation were analyzed to evaluate osseointegration procedures according to a planned medical follow-up. In the delayed group, around 6 months, a bone biopsy was taken just during implant placement in order to evaluate the new formed bone from a histological and histomorphometrical point of view. A further 6 months later, abutment connection was performed, and the patients received prosthetic restoration of the missing teeth. RESULT: Clinically, the incisions healed well. No abnormal reactions were found during follow-up period. All the 174 simultaneous implants were successful after 1-5 years of medical review; Out of 82 delayed implants, 3 were found to be loose. Histologically, all the specimens showed signs of active remodeling, and all the tissues had a large amount of osteocyte at sixth month after sinus augmentation. New bone formed dramatically. Radiologically, the density of CHA gradually reduced since the beginning of the third month, and CHA may be completely resolved at about fifth year. CONCLUSION: CHA is proven an ideal bone graft material for its reliable clinical results and favorable histocompatibility in the treatment of sinus atrophy or other kinds of insufficient bone volume in this region. Moreover, CHA's signal application can achieve desired clinical effect. CLINICAL RELEVANCE: This study shows the clinic application of CHA in maxillary sinus augmentation. Compared with popular mixture of autogenous bone and grafting materials, our results show CHA's signal application can achieve ideal osseointegration interface and satisfying clinic effect.

MicroRNA-124-5p delays the progression of cerebral aneurysm by regulating FoxO1.

Cerebral aneurysm (CA) is a common brain disease, and the development of cerebral aneurysm is driven by inflammation and hemodynamic stress. MicroRNA (miR)-124-5p is reported to be associated with inflammatory response in brain disease such as cerebral ischemia-reperfusion injury. However, the function and molecular mechanism of miR-124-5p in CA are not clear, thus, the effects of miR-124-5p on inflammatory response in CA were explored. Firstly, the expression of miR-124-5p in the peripheral blood of patients with CA and the control group was detected by reverse transcription-quantitative PCR. Then, the human umbilical vein endothelial cells (HUVECs) were used as an in vitro model system and stimulated with interleukin (IL)-1ß to simulate the inflammatory environment of CA, and the expression of miR-124-5p was detected. Next, the effect of miR-124-5p on the migration and invasion of HUVECs was detected using Transwell assays. Meanwhile, the function of miR-124-5p on various inflammatory factors was determined by western blotting and enzyme-linked immunosorbent assay (ELISA). Next, the TargetScan website was used to predict FoxO1 as a target gene of miR-124-5p, and this target association was validated by double luciferase reporter assay and western blotting. Finally, the interaction of miR-124-5p with FoxO1 in CA was measured by Transwell western blotting and ELISA assays. The results showed that the expression level of miR-124-5p in the peripheral blood of patients with CA was lower compared with that of control group, and the miR-124-5p in HUVECs stimulated by IL-1ß was less compared with that in normal HUVECs. Besides, miR-124-5p could inhibit the migration and invasion abilities of HUVECs and the release of inflammatory factors. Additionally, the overexpression of miR-124-5p was able to inhibit the expression of FoxO1. miR-124-5p-inhibitor promoted the migration and invasion of HUVECs, as well as inflammatory response, which was weakened following the introduction of FoxO1 small interfering RNA. Overall, the present study demonstrated that miR-124-5p could prevent the occurrence and development of cerebral aneurysm by downregulating the expression of FoxO1.

[A study of the infection and physicochemical characteristics of the marine fish infected by Anisakis L3 caught in Zhoushan Fishery].

OBJECTIVE: The aim of this research was to investigate the third phase Anisakis simplex larvae (Anisakis L3) infection in marine fish caught in Zhoushan Fishery and to find out its physicochemical and biological characteristics. METHODS: A total of 444 fish belonging to 29 species were dissected to isolate anisakis larvae which were then morphologically identified. The survival tolerance of Anisakis L3 were observed in various conditions, such as in different temperature and medium. RESULTS: A total of 218 fish from 21 species were infected by Anisakis simplex larvae, yielding an overall infection rate of 49.10% (218/444). Trichiurus haumela, pneumatophorus japonicus, miichthys miiuy, argyrosomus argentatus and anguilliformes had high infection rate and had an average infection intensity of 15.28 per fish. 3332 Anisakis larvae were detected in 218 fish, among which Anisakis L3 and Pseudoterranova larvae accounted for 99.46% (3314/3332) and 0.54% (18/3332) respectively. Anisakis L3 was highly resistant to common condiment. We found the liquor with high concentration of alcohol showed better insecticidal effect than that with low concentration of alcohol (t = 4.105, P < 0.05) and low concentration mebendazole composite was not only more effective than high concentration mebendazole composite (F = 45.198, P < 0.01) but also more effective than other drugs, such as albendazole and mebendazole. Anisakis L3 could live up to 9 h and 12 h at -20°C, -10°C respectively, however they were very sensitive to high temperature. It has been shown that they could only survive for less than 11 s and 1 s at 50°C and 60°C respectively. CONCLUSION: The observed Anisakis L3 infection rate in the marine fish found in Zhoushan Fishery was very high. Anisakis L3 showed high resistance to low temperature but not to high temperature.

Transmission of COVID-19 in the terminal stages of the incubation period: A familial cluster.

We report a familial cluster of 2019 novel coronavirus disease (COVID-19) to assess its potential transmission during the incubation period. The first patient in this familial cluster was identified during the presymptomatic period, as a close contact of a confirmed patient. Five family members had close contact with this first patient during his incubation period, with four of them confirmed positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the subsequent sampling tests.

Karyopherin ß1 deletion suppresses tumor growth and metastasis in colorectal cancer (CRC) by reducing MET expression.

Colorectal cancer (CRC) has become the third most common type of cancer worldwide, and CRC liver metastasis (CRLM) is associated with poor survival rates. However, the molecular mechanisms driving this phenomenon remain unclear. Karyopherin ß1 (KPNB1) is an adaptor protein that transports several proteins to the nuclear, and has been reported to play essential role in regulating many cancer-associated pathologies. Nevertheless, its role in CRC is unknown. The study was aimed to explore the role of KPNB1 as a pro-metastatic factor and to reveal the underlying mechanism. Here, the results indicated that KPNB1 expression was markedly increased in CRC samples. KPNB1 expression was gradually up-regulated with CRC development and was tightly correlated with poor prognosis in CRC patients. In vitro results demonstrated that KPNB1 decreasing markedly reduced CRC cell proliferation, migration and invasion, which was positively associated with the expression of MET proto-oncogene (MET). Further analysis revealed that KPNB1 decrease down-regulated the expression of epithelial-mesenchymal transition (EMT)-associated signals. In vivo experiments also demonstrated that KPNB1 knockdown evidently inhibited the tumor growth and metastasis in a CRC xenograft model. Importantly, we found that KPNB1 could interact with MET to modulate cell proliferation and metastasis in CRC. A subsequent mechanistic study illustrated that MET over-expression markedly eliminated KPNB1 silence-inhibited migration and invasion in CRC cells. In summary, KPNB1 deletion repressed the metastasis of CRC cells through interacting with MET, which could be served as a potential prognostic biomarker in CRC patients.

Animals as amplification hosts in the spread of severe fever with thrombocytopenia syndrome virus: A systematic review and meta-analysis.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). The seroprevalence of anti-SFTSV antibodies specific to SFTSV (IgG or IgM) has been investigated in different animal hosts in many epidemiological studies, but no systematic estimation of seroprevalence has yet been performed. Hence, this meta-analysis was conducted in order to obtain a more comprehensive result to clarify the prevalence of SFTSV in animals. METHODS: A search for all relevant articles was conducted in the major national and international electronic databases up to August 2018. Data on seroprevalence of SFTSV antibodies (IgM and IgG) were extracted as the primary outcome. The pooled seroprevalence rates and 95% confidence intervals (95% CI) were determined. RESULTS: Overall, anti-SFTSV antibodies (IgG or IgM) were detected in 15 animal species. The pooled seroprevalence of anti-SFTSV antibodies was 45.70% in goats and sheep, 36.70% in cattle, 29.50% in dogs, 9.60% in chickens, 3.20% in rodents, and 3.20% in pigs. The seroprevalence of SFTSV in animals that had a confined range was significantly lower than that in free-range animals. SFTSV RNA was detected in 11 animal species, with a carriage rate varying from 0.23% to 26.31%. CONCLUSIONS: SFTSV has a wide spectrum of animal hosts, including domestic and wild animals. The prevalence of SFTSV is high among specific animal species.

The Hydraulic Driving Mechanisms of Cyanobacteria Accumulation and the Effects of Flow Pattern on Ecological Restoration in Lake Dianchi Caohai.

Due to rapid increases in socioeconomic development and the human population over the past few decades, the shallow lakes in China have suffered from eutrophication and poor water quality. The conditions in Lake Dianchi Caohai, which is in the northern part of Lake Dianchi, are considered the most serious. The ecological restoration of Lake Dianchi Caohai began in the late 1980s. Lake managers and the public have been puzzled by the lack of a significant response of the water quality to the flow pattern despite the tremendous investment in water quality improvements. Therefore, lake managers desperately need to understand the responses of pollutant behaviors to proposed management measures. In this paper, a depth-averaged two-dimensional hydrodynamic and water quality model based on hydrological data, measured lake bed elevation, and water quality data is developed to simulate the flow field and water quality of Lake Dianchi Caohai. This model was validated using water quality data from the Caohaizhongxin site in 2016, and a close agreement was found between the model results and observations. Wind-driven circulation in Lake Dianchi Caohai was observed in the model results, which revealed that the lake flow pattern was dominated by wind-driven circulation, while the inflow/outflow played only a subsidiary role during this period. The formation of the wind-driven current in Lake Dianchi Caohai could be roughly divided into three stages. The hydrodynamic processes connected with the distribution of chlorophyll a are evaluated and discussed to adequately understand the hydraulic mechanisms driving the accumulation of cyanobacteria. Moreover, we designed three scenarios after comparing all possible operation scenarios to analyze the contributions of each different operation scenario to the water quality improvements. The optimal ecological operation scenario which has the best impacts on the water quality, especially the reduction in Chla and NH3-N concentration, is proposed based on our comprehensive analysis. The water quality improvement and management suggestions proposed in this paper are based on lake flow patterns and make up for previous studies that did not consider the effects of hydraulic characteristics on water quality improvement in Lake Dianchi Caohai.

Molecular epidemiology and spatiotemporal dynamics of norovirus associated with sporadic acute gastroenteritis during 2013-2017, Zhoushan Islands, China.

A total of 1 590 fecal swabs and stool samples from sporadic acute gastroenteritis patients of all ages were collected from January 2013 to March 2018 in the Zhoushan Islands, China, with 99 (6.23%) samples subsequently identified as human norovirus (HuNoV) positive. Phylogenetic analysis of partial RdRp and VP1 gene regions identified 10 genotypes of the GII genogroup and 3 genotypes of the GI genogroup. The predominant genotype was GII.P17-GII.17 (42.86%, 33/77), followed by GII.Pe-GII.4_Sydney 2012 (24.68%, 19/77) and GII.P16-GII.2 (12.96%, 10/77). However, the prevailing genotype in the Zhoushan Islands has shifted on three separate occasions. The GII.Pe-GII.4_Sydney_2012 strain was dominant in 2013-2014, the GII.P17-17 strain was dominant in 2015-2016, and the GII.P16-GII.2 strain was dominant in 2017. Divergence analysis showed that the re-emerging GII.P16-GII.2 strains clustered with the Japanese 2010-2012 GII.P16-GII.2 strains, and the time of the most recent common ancestor was estimated to have occurred in 2012 to 2013. The evolutionary rates of the RdRp gene region of the GII.P16 genotype and the VP1 gene region of the GII.2 genotype were 2.64 × 10(-3) (95% HPD interval, 2.17-3.08 × 10(-3)) and 3.36 × 10(-3) (95% HPD interval, 2.66-4.04 × 10(-3)) substitutions/site/year, respectively. The migration pattern of the HuNoV GII.2 genotype in China demonstrated that the re-emerging GII.P16-GII.2 strains were first introduced into Hong Kong from Japan, and then spread from Hong Kong to other coastal areas. Our results also showed that the GII.P16-GII.2 strains in the Zhoushan Islands were likely introduced from Jiangsu Province, China, in 2016.

Seroprevalence of severe fever with thrombocytopenia syndrome virus in China: A systematic review and meta-analysis.

OBJECTIVE: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus-SFTSV. The seroprevalence of anti-SFTSV antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM), specific to SFTSV in the general population has been investigated in various epidemiological studies with inconsistent results. Here, we clarify this discrepancy and reach a more comprehensive result by mean of a meta-analysis. METHODS: All relevant articles were searched in the electronic databases (PubMed, Web of science, Embase, Chinese National Knowledge Infrastructure database, Chinese Wanfang database) up to November 2016. The pooled seroprevalence and 95% confidence intervals (95% CIs) were calculated by random- or fixed- model on the basis of heterogeneity. RESULTS: In total, 21 studies containing 23,848 blood samples from 7 provinces were included in this meta-analysis. The minimum and maximum reported seroprevalences of SFTSV among humans in China were 0.23% and 9.17%, respectively. The overall pooled seroprevalence of SFTSV antibodies was 4.3% (95%CI: 3.2%-5.5%). The pooled prevalence was 5.9% (95%CI: 4.7%-7.0%) in Zhejiang province, 4.9% (95%CI: 4.1-5.8%) in Anhui province, 3.9% (95%CI: 1.3%-6.4%) in Shandong province, and 0.7% (95%CI: 0.2%-1.1%) in Jiangsu province. Stratified by occupation, the pooled prevalence of farmer was 6.1% (95%CI: 3.4%-8.9%) and others (mainly are students) was 3.3% (95%CI: 2.4%-4.2%). Additionally, seroprevalence of SFTSV in people who lived in the same village with the patient were higher than that of people who lived in a different village. Seropositive rates in sampling years after 2012 were higher than that before 2012. The prevalence of SFTSV did not differ by age or gender. Sensitive analysis by omitting one study at a time indicated the results of the pooled seroprevalence were robust. CONCLUSIONS: Seroprevalence of SFTSV among healthy population in central and eastern China is high. Surveillance efforts on mild or asymptomatic infections among endemic persons are needed.

Effect of total dissolved gas supersaturated water on early life of David's schizothoracin (Schizothorax davidi).

The effect of total dissolved gas (TDG) supersaturation on fish living downstream of dams is one of the main ecological risks of high dam construction. A strategy for mitigating the negative effects is needed urgently since many high dams are under construction in the upper reaches of the Yangtze River in China. Experiments on the hatching process of David's schizothoracin were carried out and the results show that the hatching rate decreased with increasing TDG levels, and that most eggs hatched within a very short time in the higher TDG saturation groups. By using a stereomicroscope, damages to the head, yolk sac, body, anus, etc. were found in larvae which hatched in TDG supersaturated water. Results show that the lesion rate increased with increasing TDG levels. Furthermore, 7-d-old David's schizothoracin were exposed to TDG supersaturated water levels of 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, and 140% for testing their tolerance to TDG supersaturation. We found that the median lethal concentrations (LC50) for 13, 14, 20, 35, 52, 73, and 96 h exposure were 138%, 138%, 134%, 130%, 129%, 128%, and 126%, respectively. The median lethal times (LT50) were 7.49, 11.04, 19.25, and 35.38 h for exposure to water with TDG levels of 145%, 140%, 135%, and 130%, respectively.

Effects of total dissolved gas supersaturated water on lethality and catalase activity of Chinese sucker (Myxocyprinus asiaticus Bleeker).

Total dissolved gas (TDG) supersaturation caused by dam sluicing can result in gas bubble trauma (GBT) in fish and threaten their survival. In the present study, Chinese suckers (Myxocyprinus asiaticus Bleeker) were exposed to TDG supersaturated water at levels ranging from 120% to 145% for 48 h. The median lethal concentration (LC(50)) and the median lethal time (LT(50)) were determined to evaluate acute lethal effects on Chinese suckers. The results showed that the LC(50) values of 4, 6, 8, and 10 h were 142%, 137%, 135%, and 130%, respectively. The LT(50) values were 3.2, 4.7, 7.8, 9.2, and 43.4 h, respectively, when TDG supersaturated levels were 145%, 140%, 135%, 130%, and 125%. Furthermore, the biological responses in Chinese suckers were studied by assaying the catalase (CAT) activities in gills and muscles at the supersaturation level of 140% within LT(50). The CAT activities in the gills and muscle tissues exhibited a regularity of a decrease after an increase. CAT activities in the muscles were increased significantly at 3/5LT(50) (P<0.05) and then came back to the normal level. However, there were no significant differences between the treatment group (TDG level of 140%) and the control group (TDG level of 100%) on CAT activities in the gills before 3/5LT(50) (P>0.05), but the activities were significantly lower than the normal level at 4/5LT(50) and LT(50) (P<0.05).

Growth rate, catalase and superoxide dismutase activities in rock carp (Procypris rabaudi Tchang) exposed to supersaturated total dissolved gas.

Total dissolved gas supersaturation (TDGS) appears when the pressures of gases in a solution exceed the barometric pressures. TDGS is often caused by flood discharge at dams. It may lead to gas bubble disease (GBD) for fish and biochemical responses of selected fish and other aquatic organisms. The purpose of this study was to determine the impact of long-term TDGS levels on the growth and biochemical responses of rock carp (Procypris rabaudi Tchang) dwelling in the upper reaches of the Yangtze River. Three-year-old rock carp were exposed to TDGS levels at 100%, 104%, 108%, 112%, and 116% for 42 d. Samples were taken every 7 d after the start of the trial in order to determine catalase (CAT) and superoxide dismutase (SOD) activities in gill and muscle tissues. Samples were taken at Days 0 and 42 of exposure to determine growth rate. Little effect was found on growth rate in all treatment groups. SOD and CAT activities varied in different tissues, according to time of exposure and TDGS levels. The biochemical response of fish exposed to TDGS was more obvious in gill tissue than in muscle tissue. Surveys of SOD and CAT activities in different tissues offer important information about the effect of TDGS on the rare fish in the Yangtze River, and may help evaluate the risk to the aquatic eco-environment and aquatic ecosystem in the downstream of the Yangtze River.

Matrix metalloproteinase inhibitors: a review on bioanalytical methods, pharmacokinetics and metabolism.

Enzymes are major drug targets in drug discovery and development processes in the pharmaceutical and biotechnology industry. A recent survey found that nearly half of all the marketed small-molecule drugs are inhibitors of enzymes. Matrix metalloproteinases (MMPs) are a family of 28 enzymes capable of degrading the constituents of the extracellular matrix (ECM) and the basement-membrane. MMPs play an essential role in several normal physiological processes including growth, wound healing and tissue repair. Over-expression and activation of MMPs has been linked to a range of diseases which include osteoarthritis, tumor metastasis, angiogenesis and cardiovascular diseases. The development of MMP inhibitors as therapeutic agents has kept an important place in drug discovery. Therefore, there is also an increasing need for robust analytical methods for evaluation of inhibitory potency and for the analysis of MMP inhibitors and their metabolites which can even play a more significant role than the parent drug. Modern analytical techniques and hyphenated instrumentations such as liquid chromatography-mass spectrometry with a function of structure elucidation can provide a profound insight into the research of MMP inhibitors and also serve as a complementary method to zymographic techniques for the analysis of biological samples. This review mainly summarizes bioanalytical methods, pharmacokinetics and related metabolites of MMP inhibitors over the last 12 years.

Effects of gas supersaturation on lethality and avoidance responses in juvenile rock carp (Procypris rabaudi Tchang).

Laboratory experiments were conducted to determine the effects of total dissolved gas (TDG) supersaturation on acute lethality and avoidance responses in juvenile rock carp (Procypris rabaudi Tchang). The juvenile rock carp were exposed to water with different levels of supersaturation (105%, 115%, 120%, 125%, 130%, 135%, 140%, and 145%) and depth of 0.20 m at 25 °C for 60 h. Median lethal time (LT(50)) was used to assess the lethal responses corresponding to different levels of gas supersaturation. The results show that half of the juvenile rock carp died at the 120%, 125%, 130%, 135%, 140%, and 145% levels of supersaturation, and the LT(50) corresponding to different levels of supersaturation was 18.7, 15.4, 8.2, 6.6, 3.5, and 1.7 h. When the level of supersaturated water is below 115%, the mortality is negligible. Avoidance responses were observed 5 min after the fish were put into equilibrated water (99%, 0.08 m deep) and water with different supersaturated levels (105%, 115%, 125%, 135%, and 145%, 0.08 m deep) at 25 °C. The fish exhibited strong avoidance responses in supersaturated water when the gas supersaturation was above 135%. However, they exhibited an obvious preference to supersaturated water when the gas supersaturation was below 115%. Thus, the juvenile rock carp can likely survive in water with a supersaturated level of 115%.