AIM: To compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for the treatment of colorectal tumors.
AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 5...AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.展开更多
Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin i...Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups： ischemia（cerebral ischemia and reperfusion）, valproic acid（cerebral ischemia and reperfusion ＋ three intraperitoneal injections of valproic acid; positive control）, and baicalin（cerebral ischemia and reperfusion ＋ intraperitoneal injection of baicalin for 21 days）. Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride（TTC） staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.展开更多
Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been consider...Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.展开更多
AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was ind...AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy.Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell （HSC） line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chainreaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, thencollagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated withor without platelet-derived growth factor （PDGF）-BB at a final concentration of 20μg/L and the cell growthwas determined by MTS conversion.RESULTS： In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significantpositive correlation with collagen type I levels.In HSC-T6 cells transfected with RNAi targeted top90RSK, the expression of collagen type I was down-regulated （61.8% in mRNA, P 〈 0.01, 89.1% inprotein, P 〈 0.01）. However, collagen type ] promoteractivity was not increased with over-expression of p90RSK and not decreased with low expression either,compared with controls in the same cell line （P = 0.076）.Furthermore, p90RSK siRNA exerted the inhibitionof HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation.CONCLUSION： p90RSK is over-expressed in activatedHSCs and involved in regulating the abnormalexpression of collagen type I through initiating theproliferation of HSCs.展开更多
Objective:To study the inhibition effect of siRNA on the expression of Wisp-1 gene in Hca-F of mouse hepatocellular carcinoma cells strain and also its effect on the proliferation,migration and adhesion of hepatocellu...Objective:To study the inhibition effect of siRNA on the expression of Wisp-1 gene in Hca-F of mouse hepatocellular carcinoma cells strain and also its effect on the proliferation,migration and adhesion of hepatocellular carcinoma cells.Methods:Three expression vectors of siRNA were constructed.Lipo2000 was employed to transfect Hca-F cells and Western blot was used to detect the inhibition effect of siRNA on the expression of Wisp-1 gene.Afterwards,CCK8 was adopted to detect the effect of Wisp-1 siRNA on the proliferation of Hca-F cells;Annexin V-FTTC/PI double staining flow cytometry was used to detect the effect of Wisp-1 siRNA on the apoptosis of Hca-F cells;Transwell was used to detect the effect of Wisp-1 siRNA on the migration of Hca-F cells.The in vitro cell adhesion kit was used to detect of Wisp-1 siRNA on the change in the components of extracellular matrix to which Hca-F cells adhered.Western blot was used to detect the activation of protein kinase B(AKT)/glycogen synthase kinase-3(3pathway and the expression of downstream target protein p53 and matrix metal!oproteinases-2.Results:The siRNA showed interference effect on the expression of Wisp-1 gene.Compared with the control group,after being transfected to cells,Wisp-1 siRNA could significantly inhibit the proliferation,migration and adhesion of Hca-F cells and also promote the cell apoptosis,which was related to the down-regulated phosphorylation of AKT and glycogen synthase kinase-3β and the expression of p53 and matrix metalIoproteinases-2(P<0.05).Conclusions:The inhibition of Wisp-1 expression can reduce the proliferation,migration and adhesion of mouse hepatocellular carcinoma cells,which is related to the AKT/ glycogen synthase kinase-3 β pathway.Wisp-1 gene may be the potential target to cure the hepatocellular carcinoma.展开更多
The impact of droplets on the liquid film is widely involved in industrial and agricultural fields.In recent years,plenty of works are limited to dry walls or stationary liquid films,and the research of multi-droplet ...The impact of droplets on the liquid film is widely involved in industrial and agricultural fields.In recent years,plenty of works are limited to dry walls or stationary liquid films,and the research of multi-droplet impact dynamic films is not sufficient.Based on this,this paper employs a coupled level set and volume of fluid(CLSVOF) method to numerically simulate two-droplet impingement on a dynamic liquid film.In our work,the dynamic film thickness,horizontal central distance between the droplets,droplets’ initial impact speed,and simultaneously the flow velocity of the moving film are analyzed.The evolution phenomenon and mechanism caused by the collision are analyzed in detail.We find that within a certain period of time,the droplet spacing does not affect the peripheral crown height;when the droplet spacing decreases or the initial impact velocity increases,the height of the peripheral crown increases at the beginning,and then,because the crown splashed under Rayleigh-Plateau instability,this results in the reduction of the crown height.At the same time,it is found that when the initial impact velocity increases,the angle between the upstream peripheral jet and the dynamic film becomes larger.The more obvious the horizontal movement characteristics,the more restrained the crown height;the spread length increases with the increase of the dynamic film speed,droplet spacing and the initial impact velocity.When the liquid film is thicker,more fluid enters the crown,due to the crown being unstable,the surface tension is not enough to overcome the weight of the rim at the end of the crown,resulting in droplets falling off.展开更多
The supersonic gas-jet target is an important experimental target for laser wakefield acceleration(LWFA),which has great potential for driving novel radiation sources such as betatron radiation and Compton scattering ...The supersonic gas-jet target is an important experimental target for laser wakefield acceleration(LWFA),which has great potential for driving novel radiation sources such as betatron radiation and Compton scattering gamma rays.According to different electron acceleration requirements,it is necessary to provide specific supersonic gas jets with different density profiles to generate electron beams with high quality and high repetition rates.In this study,the interference images and density profiles of different gas-jet targets were obtained through a modified Nomarski interference diagnosis system.The relationships between the gas density and back pressure,nozzle structure,and other key parameters were studied.Targets with different characteristics are conducive to meeting the various requirements of LWFA.展开更多
Objective:To explore the effect of Ramipril on renin-angiotensin-aldosterone system of young and middle-aged patients with hypertension.Methods 90 young and middle-aged patients with hypertension who had been seeking ...Objective:To explore the effect of Ramipril on renin-angiotensin-aldosterone system of young and middle-aged patients with hypertension.Methods 90 young and middle-aged patients with hypertension who had been seeking treatment in the hospital between August 2017 and August 2018 were selected and randomly divided into a control group and an observation group according to the random number table,with 45 cases in each group.The control group received Amlodipine for treatment,whereas the observation group was given Amlodipine combined with Ramipril for treatment.The hemodynamic indexes,blood lipid,blood pressure,angiotensinⅡ(AngⅡ),plasma renin(PRA),aldosterone(ALD)levels and incidence of adverse reactions during the medication in the two groups were compared before and after treatment.Results After treatment,thefibrinogen,plasma viscosity and whole blood viscosity in the observation group were significantly higher than those in the control group,with statistically significant difference between the two groups(P<0.05);total cholesterol(TC),triacylglycerol(TG)and low density lipoprotein cholesterin(LDL-C)in the observation group were significantly lower than those in the control group,and statistically significant difference was registered between the two groups(P<0.05);the diastolic pressure and systolic pressure in the observation group were decreased more significantly compared with the control group,with statistically significant difference shown between the two groups(P<0.05);the AngⅡ,ALD and PRA levels in the observation group were significantly lower than the control group,and the difference between two groups were statistically significant(P<0.05);during the medication,no significant bleeding or liver and kidney function damages occurred in the two groups.Conclusions For young and middle-aged patients with hypertension,the treatment with Ramipril,which is of high safety,can effectively improve the activity of their renin-angiotensin-aldosterone system,reduce the level of blood pressure and AngⅡ,ALD and PRA levels.展开更多
Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter...Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor microbiosphere.Currently,the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is unknown.Here,analyses of carbon isotope composition in a~750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition,with anomalous ^(14)C ages likely caused by seismically driven mass transport and the funneling effect of trench geomorphology.Microbial community composition and diverse enzyme activities in the upper~27 cm differed from those at lower depths,probably due to sudden sediment deposition and differences in redox condition and organic matter availability.At lower depths,microbial population numbers,and composition remained relatively constant,except at some discrete depths with altered enzyme activity and microbial phyla abundance,possibly due to additional sudden sedimentation events of different magnitude.Evidence is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth’s deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic populations.Such depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere.展开更多
The majority of marine ammonia oxidizers belong to Thaumarchaeota,a phylum of Archaea,which is distributed throughout the water column.Marine surface waters contain distinct thaumarchaeotal phylotypes compared to the ...The majority of marine ammonia oxidizers belong to Thaumarchaeota,a phylum of Archaea,which is distributed throughout the water column.Marine surface waters contain distinct thaumarchaeotal phylotypes compared to the deeper ocean,but spatial dynamics of the surface-associated lineages are largely unsolved.This study of 120 seawater samples from the eastern Chinese marginal seas identifed contrasting distribution and association patterns among thaumarchaeotal phylotypes across diferent dimensions.Horizontally,Nitrosopumilus-like and Nitrosopelagicus-like phylotypes dominated the surface water(3 m)of the Yellow Sea(YS)and East China Sea(ECS),respectively,along with increased abundance of total free-living Thaumarchaeota in ECS.Similar compositional changes were observed in the surface microlayer.The spatial heterogeneity of particle-attached Thaumarchaeota was less clear in surface microlayers than in surface waters.Vertically,the Nitrosopelagicus-like phylotype increased in abundance from surface to 90 m in ECS,which led to an increase in the proportion of Thaumarchaeota relative to total prokaryotes.This occurred mainly in the free-living fraction.These results indicate a clear size-fractionated niche partitioning,which is more pronounced at lower depths than in the surface water/surface microlayer.In addition,associations of Thaumarchaeota with other microbial taxa varied between phylotypes and size fractions.Our results show that a phylotype-resolved and size-fractionated spatial heterogeneity of the thaumarchaeotal community is present in surface oceanic waters and a vertical variation of the Nitrosopelagicus-like phylotype is present in shallow shelf waters.展开更多
Microbial lysis of dimethylsulfoniopropionate(DMSP)is a key step in marine organic sulfur cycling and has been recently demonstrated to play an important role in mediating interactions between bacteria,algae,and zoopl...Microbial lysis of dimethylsulfoniopropionate(DMSP)is a key step in marine organic sulfur cycling and has been recently demonstrated to play an important role in mediating interactions between bacteria,algae,and zooplankton.To date,microbes that have been found to lyse DMSP are largely confined to free‐living and surface‐attached bacteria.In this study,we report for the first time that a symbiont(termed“Rhodobiaceae bacterium HWgs001”)in the gill of the marine scallop Argopecten irradians irradians can lyse and metabolize DMSP.Analysis of 16S rRNA gene sequences suggested that HWgs001 accounted for up to 93%of the gill microbiota.Microscopic observations suggested that HWgs001 lived within the gill tissue.Unlike symbionts of other bivalves,HWgs001 belongs to Alphaproteobacteria rather than Gammaproteobacteria,and no genes for carbon fixation were identified in its small genome.Moreover,HWgs001 was found to possess a dddP gene,responsible for the lysis of DMSP to acrylate.The enzymatic activity of dddP was confirmed using the heterologous expression,and in situ transcription of the gene in scallop gill tissues was demonstrated using reverse‐transcription PCR.Together,these results revealed a taxonomically and functionally unique symbiont,which represents the first‐documented DMSP‐metabolizing symbiont likely to play significant roles in coastal marine ecosystems.展开更多
Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity,...Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism.MethodsA high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator.ResultsThe expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC–MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin.ConclusionsAdipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.展开更多
Dimethyl sulfide(DMS) is the most abundant form of volatile sulfur in Earth’s oceans, and is mainly produced by the enzymatic clevage of dimethylsulfoniopropionate(DMSP). DMS and DMSP play important roles in driving ...Dimethyl sulfide(DMS) is the most abundant form of volatile sulfur in Earth’s oceans, and is mainly produced by the enzymatic clevage of dimethylsulfoniopropionate(DMSP). DMS and DMSP play important roles in driving the global sulfur cycle and may affect climate. DMSP is proposed to serve as an osmolyte, a grazing deterrent, a signaling molecule, an antioxidant, a cryoprotectant and/or as a sink for excess sulfur. It was long believed that only marine eukaryotes such as phytoplankton produce DMSP. However, we recently discovered that marine heterotrophic bacteria can also produce DMSP, making them a potentially important source of DMSP. At present, one prokaryotic and two eukaryotic DMSP synthesis enzymes have been identified.Marine heterotrophic bacteria are likely the major degraders of DMSP, using two known pathways: demethylation and cleavage.Many phytoplankton and some fungi can also cleave DMSP. So far seven different prokaryotic and one eukaryotic DMSP lyases have been identified. This review describes the global distribution pattern of DMSP and DMS, the known genes for biosynthesis and cleavage of DMSP, and the physiological and ecological functions of these important organosulfur molecules, which will improve understanding of the mechanisms of DMSP and DMS production and their roles in the environment.展开更多
文摘AIM: To compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for the treatment of colorectal tumors.
基金Supported by Jinling Hospital Research Fund,No.2013064
文摘AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.
基金supported by the Cross Foundation Major Project of Engineering and Medicine of Shanghai Jiao Tong University,No.YG2016MS50(to JD)Foundation for Fostering Project of Clinical Study on Multi-disciplinary Team of Renji Hospital,No.PYMDT-012(to JD)
文摘Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups： ischemia（cerebral ischemia and reperfusion）, valproic acid（cerebral ischemia and reperfusion ＋ three intraperitoneal injections of valproic acid; positive control）, and baicalin（cerebral ischemia and reperfusion ＋ intraperitoneal injection of baicalin for 21 days）. Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride（TTC） staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.
基金supported by the National Natural Science Foundation of China,Nos.82071283(to QH)and 81671130(to QH)Medical Engineering Cross Research Foundation of Shanghai Jiao Tong University of China,No.YG2017MS83(to QH)from Shanghai Municipal Science and Technology Commission Medical Guidance Science and Technology Support Project of China,No.19411968400(to QYM).
文摘Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.
基金Supported by Jinling Hospital Medical Research Fund, No. 2005029
文摘AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy.Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell （HSC） line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chainreaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, thencollagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated withor without platelet-derived growth factor （PDGF）-BB at a final concentration of 20μg/L and the cell growthwas determined by MTS conversion.RESULTS： In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significantpositive correlation with collagen type I levels.In HSC-T6 cells transfected with RNAi targeted top90RSK, the expression of collagen type I was down-regulated （61.8% in mRNA, P 〈 0.01, 89.1% inprotein, P 〈 0.01）. However, collagen type ] promoteractivity was not increased with over-expression of p90RSK and not decreased with low expression either,compared with controls in the same cell line （P = 0.076）.Furthermore, p90RSK siRNA exerted the inhibitionof HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation.CONCLUSION： p90RSK is over-expressed in activatedHSCs and involved in regulating the abnormalexpression of collagen type I through initiating theproliferation of HSCs.
基金supported by Shandong Scientific and Technological Development Project Fund(No.2013GSF11825)
文摘Objective:To study the inhibition effect of siRNA on the expression of Wisp-1 gene in Hca-F of mouse hepatocellular carcinoma cells strain and also its effect on the proliferation,migration and adhesion of hepatocellular carcinoma cells.Methods:Three expression vectors of siRNA were constructed.Lipo2000 was employed to transfect Hca-F cells and Western blot was used to detect the inhibition effect of siRNA on the expression of Wisp-1 gene.Afterwards,CCK8 was adopted to detect the effect of Wisp-1 siRNA on the proliferation of Hca-F cells;Annexin V-FTTC/PI double staining flow cytometry was used to detect the effect of Wisp-1 siRNA on the apoptosis of Hca-F cells;Transwell was used to detect the effect of Wisp-1 siRNA on the migration of Hca-F cells.The in vitro cell adhesion kit was used to detect of Wisp-1 siRNA on the change in the components of extracellular matrix to which Hca-F cells adhered.Western blot was used to detect the activation of protein kinase B(AKT)/glycogen synthase kinase-3(3pathway and the expression of downstream target protein p53 and matrix metal!oproteinases-2.Results:The siRNA showed interference effect on the expression of Wisp-1 gene.Compared with the control group,after being transfected to cells,Wisp-1 siRNA could significantly inhibit the proliferation,migration and adhesion of Hca-F cells and also promote the cell apoptosis,which was related to the down-regulated phosphorylation of AKT and glycogen synthase kinase-3β and the expression of p53 and matrix metalIoproteinases-2(P<0.05).Conclusions:The inhibition of Wisp-1 expression can reduce the proliferation,migration and adhesion of mouse hepatocellular carcinoma cells,which is related to the AKT/ glycogen synthase kinase-3 β pathway.Wisp-1 gene may be the potential target to cure the hepatocellular carcinoma.
基金Project supported by the Engineering Research Center of Eco-environment in the Three Gorges Reservoir Region(Grant No.KF2019-10)。
文摘The impact of droplets on the liquid film is widely involved in industrial and agricultural fields.In recent years,plenty of works are limited to dry walls or stationary liquid films,and the research of multi-droplet impact dynamic films is not sufficient.Based on this,this paper employs a coupled level set and volume of fluid(CLSVOF) method to numerically simulate two-droplet impingement on a dynamic liquid film.In our work,the dynamic film thickness,horizontal central distance between the droplets,droplets’ initial impact speed,and simultaneously the flow velocity of the moving film are analyzed.The evolution phenomenon and mechanism caused by the collision are analyzed in detail.We find that within a certain period of time,the droplet spacing does not affect the peripheral crown height;when the droplet spacing decreases or the initial impact velocity increases,the height of the peripheral crown increases at the beginning,and then,because the crown splashed under Rayleigh-Plateau instability,this results in the reduction of the crown height.At the same time,it is found that when the initial impact velocity increases,the angle between the upstream peripheral jet and the dynamic film becomes larger.The more obvious the horizontal movement characteristics,the more restrained the crown height;the spread length increases with the increase of the dynamic film speed,droplet spacing and the initial impact velocity.When the liquid film is thicker,more fluid enters the crown,due to the crown being unstable,the surface tension is not enough to overcome the weight of the rim at the end of the crown,resulting in droplets falling off.
基金This work was supported by the Programs for the National Natural Science Foundation of China(Nos.11975316,11775312,12005305 and 61905287)the Continue Basic Scientific Research Project(Nos.WDJC-2019-02 and BJ20002501).
文摘The supersonic gas-jet target is an important experimental target for laser wakefield acceleration(LWFA),which has great potential for driving novel radiation sources such as betatron radiation and Compton scattering gamma rays.According to different electron acceleration requirements,it is necessary to provide specific supersonic gas jets with different density profiles to generate electron beams with high quality and high repetition rates.In this study,the interference images and density profiles of different gas-jet targets were obtained through a modified Nomarski interference diagnosis system.The relationships between the gas density and back pressure,nozzle structure,and other key parameters were studied.Targets with different characteristics are conducive to meeting the various requirements of LWFA.
基金Shijiazhuang science and technology bureau guidance plan project 2016(No.151461503).
文摘Objective:To explore the effect of Ramipril on renin-angiotensin-aldosterone system of young and middle-aged patients with hypertension.Methods 90 young and middle-aged patients with hypertension who had been seeking treatment in the hospital between August 2017 and August 2018 were selected and randomly divided into a control group and an observation group according to the random number table,with 45 cases in each group.The control group received Amlodipine for treatment,whereas the observation group was given Amlodipine combined with Ramipril for treatment.The hemodynamic indexes,blood lipid,blood pressure,angiotensinⅡ(AngⅡ),plasma renin(PRA),aldosterone(ALD)levels and incidence of adverse reactions during the medication in the two groups were compared before and after treatment.Results After treatment,thefibrinogen,plasma viscosity and whole blood viscosity in the observation group were significantly higher than those in the control group,with statistically significant difference between the two groups(P<0.05);total cholesterol(TC),triacylglycerol(TG)and low density lipoprotein cholesterin(LDL-C)in the observation group were significantly lower than those in the control group,and statistically significant difference was registered between the two groups(P<0.05);the diastolic pressure and systolic pressure in the observation group were decreased more significantly compared with the control group,with statistically significant difference shown between the two groups(P<0.05);the AngⅡ,ALD and PRA levels in the observation group were significantly lower than the control group,and the difference between two groups were statistically significant(P<0.05);during the medication,no significant bleeding or liver and kidney function damages occurred in the two groups.Conclusions For young and middle-aged patients with hypertension,the treatment with Ramipril,which is of high safety,can effectively improve the activity of their renin-angiotensin-aldosterone system,reduce the level of blood pressure and AngⅡ,ALD and PRA levels.
基金supported by the Laoshan laboratory(LSKJ202203206)National Natural Science Foundation of China(92051115 and 42230412)+1 种基金the Fundamental Research Funds for the Central Universities(202172002 and 202141009)the Shandong Province Natural Science Foundation(ZR2022YQ38).
文摘Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor microbiosphere.Currently,the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is unknown.Here,analyses of carbon isotope composition in a~750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition,with anomalous ^(14)C ages likely caused by seismically driven mass transport and the funneling effect of trench geomorphology.Microbial community composition and diverse enzyme activities in the upper~27 cm differed from those at lower depths,probably due to sudden sediment deposition and differences in redox condition and organic matter availability.At lower depths,microbial population numbers,and composition remained relatively constant,except at some discrete depths with altered enzyme activity and microbial phyla abundance,possibly due to additional sudden sedimentation events of different magnitude.Evidence is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth’s deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic populations.Such depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere.
基金We thank the scientists and crews on the R/V Dongfanghong 2 for their assistance with sampling during the cruises.We thank Chunying Liu and Guipeng Yang both of the Ocean University of China for providing pH and DO data,respectively.This work was funded by the National Natural Science Foundation of China(92051115,41976101,92251303 and 41730530)the Scientifc and Technological Innovation Project of Laoshan Laboratory(LSKJ202203206 and LSKJ202203201)+2 种基金the Shandong Provincial Natural Science Foundation(ZR2022YQ38)the National Key Research and Development Program of China(2018YFE0124100)the Fundamental Research Funds for the Central Universities(202141009 and 202172002).
文摘The majority of marine ammonia oxidizers belong to Thaumarchaeota,a phylum of Archaea,which is distributed throughout the water column.Marine surface waters contain distinct thaumarchaeotal phylotypes compared to the deeper ocean,but spatial dynamics of the surface-associated lineages are largely unsolved.This study of 120 seawater samples from the eastern Chinese marginal seas identifed contrasting distribution and association patterns among thaumarchaeotal phylotypes across diferent dimensions.Horizontally,Nitrosopumilus-like and Nitrosopelagicus-like phylotypes dominated the surface water(3 m)of the Yellow Sea(YS)and East China Sea(ECS),respectively,along with increased abundance of total free-living Thaumarchaeota in ECS.Similar compositional changes were observed in the surface microlayer.The spatial heterogeneity of particle-attached Thaumarchaeota was less clear in surface microlayers than in surface waters.Vertically,the Nitrosopelagicus-like phylotype increased in abundance from surface to 90 m in ECS,which led to an increase in the proportion of Thaumarchaeota relative to total prokaryotes.This occurred mainly in the free-living fraction.These results indicate a clear size-fractionated niche partitioning,which is more pronounced at lower depths than in the surface water/surface microlayer.In addition,associations of Thaumarchaeota with other microbial taxa varied between phylotypes and size fractions.Our results show that a phylotype-resolved and size-fractionated spatial heterogeneity of the thaumarchaeotal community is present in surface oceanic waters and a vertical variation of the Nitrosopelagicus-like phylotype is present in shallow shelf waters.
基金supported by the Key Research and Development Program of Shandong Province(No.2021 ZLGX03)the start-up fund from Ocean University of China(No.862101013141).
文摘Microbial lysis of dimethylsulfoniopropionate(DMSP)is a key step in marine organic sulfur cycling and has been recently demonstrated to play an important role in mediating interactions between bacteria,algae,and zooplankton.To date,microbes that have been found to lyse DMSP are largely confined to free‐living and surface‐attached bacteria.In this study,we report for the first time that a symbiont(termed“Rhodobiaceae bacterium HWgs001”)in the gill of the marine scallop Argopecten irradians irradians can lyse and metabolize DMSP.Analysis of 16S rRNA gene sequences suggested that HWgs001 accounted for up to 93%of the gill microbiota.Microscopic observations suggested that HWgs001 lived within the gill tissue.Unlike symbionts of other bivalves,HWgs001 belongs to Alphaproteobacteria rather than Gammaproteobacteria,and no genes for carbon fixation were identified in its small genome.Moreover,HWgs001 was found to possess a dddP gene,responsible for the lysis of DMSP to acrylate.The enzymatic activity of dddP was confirmed using the heterologous expression,and in situ transcription of the gene in scallop gill tissues was demonstrated using reverse‐transcription PCR.Together,these results revealed a taxonomically and functionally unique symbiont,which represents the first‐documented DMSP‐metabolizing symbiont likely to play significant roles in coastal marine ecosystems.
基金National Natural Science Foundation of China(82070398,81922008)Key Basic Research Projects of Basic Strengthening Plan(2022-JCJQ-ZD-095-00)Top Young Talents Special Support Program in Shaanxi Province(2020).
文摘Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism.MethodsA high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator.ResultsThe expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC–MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin.ConclusionsAdipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.
基金supported by the National Natural Science Foundation of China (91751202 and 41730530)the National Key Research and Development Program of China (2016YFA0601303 and 2018YFC0310701)+1 种基金the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao) (2018SDKJ0406-4)Natural Environmental Research Council grants (NE/ N002385, NE/P012671 and NE/S001352) fund ARJC and JDT
文摘Dimethyl sulfide(DMS) is the most abundant form of volatile sulfur in Earth’s oceans, and is mainly produced by the enzymatic clevage of dimethylsulfoniopropionate(DMSP). DMS and DMSP play important roles in driving the global sulfur cycle and may affect climate. DMSP is proposed to serve as an osmolyte, a grazing deterrent, a signaling molecule, an antioxidant, a cryoprotectant and/or as a sink for excess sulfur. It was long believed that only marine eukaryotes such as phytoplankton produce DMSP. However, we recently discovered that marine heterotrophic bacteria can also produce DMSP, making them a potentially important source of DMSP. At present, one prokaryotic and two eukaryotic DMSP synthesis enzymes have been identified.Marine heterotrophic bacteria are likely the major degraders of DMSP, using two known pathways: demethylation and cleavage.Many phytoplankton and some fungi can also cleave DMSP. So far seven different prokaryotic and one eukaryotic DMSP lyases have been identified. This review describes the global distribution pattern of DMSP and DMS, the known genes for biosynthesis and cleavage of DMSP, and the physiological and ecological functions of these important organosulfur molecules, which will improve understanding of the mechanisms of DMSP and DMS production and their roles in the environment.
