Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PT...Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.展开更多
Background:Abnormal myocardial voltage-gated sodium channel 1.5(Nav1.5)expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion(I/R).Protein inhibitor of activated STAT Y(PI...Background:Abnormal myocardial voltage-gated sodium channel 1.5(Nav1.5)expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion(I/R).Protein inhibitor of activated STAT Y(PIASy)-mediated caveolin-3(Cav-3)small ubiquitin-related modifier(SUMO)modification affects Cav-3 binding to the Nav1.5.PIASy activity is increased after myocardial I/R,but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias.Methods:Using recombinant adeno-associated virus subtype 9(AAV9),rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA(shRNA).After two weeks,rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias.Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements.Results:PIASy was upregulated by I/R(P<0.01),with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density(P<0.01).AAV9-PIASy shRNA intraventricular injection into the rat heart down-regulated PIASy after I/R,at both mRNA and protein levels(P<0.05 vs.Scramble-shRNA+I/R group),decreased SUMO-modified Cav-3 levels,enhanced Cav-3 binding to Nav1.5,and prevented I/R-induced decrease of Nav1.5 and Cav-3co-localization in the intercalated disc and lateral membrane.PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias,which was reflected by a modest decrease in the duration of ventricular fibrillation(VF;P<0.05 vs.Scramble-shRNA+I/R group)and a significantly reduced arrhythmia score(P<0.01 vs.Scramble-shRNA+I/R group).The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia(VT),sustained VT and VF,especially at the time 5–10 min after ischemia(P<0.05 vs.Scramble-shRNA+IR group).Using in vitro human embryonic kidney 293 T(HEK293T)cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation(H/R),we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R.Mutation of SUMO consensus lysine sites in Cav-3(K38R or K144R)altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells.Conclusions:I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias.Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes,and subsequent ventricular arrhythmias in rats.PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.展开更多
AIM:To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stageⅢ/Ⅳgastric cancer.METHODS:A total of 53 stageⅢ/Ⅳg...AIM:To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stageⅢ/Ⅳgastric cancer.METHODS:A total of 53 stageⅢ/Ⅳgastric cancer patients were enrolled into the study and treated with neoadjuvant chemotherapy.Two of the cases were excluded.The program was as follows:75 mg/m2docetaxel and 85 mg/m2 oxaliplatin on day 1 and 1500mg/m2 fluorouracil on days 1 to 3 for three weeks.RESULTS:The tumour changes,postoperative remission rate,changes in the symptoms and adverse reactions were observed.The overall clinical efficacy(com-plete remission+partial remission)of the neoadjuvant chemotherapy was 62.7%.R0 radical resection was performed on 60.8%of the patients,with a remission rate(pathological complete response+pathological subtotal response+pathological partial response)of74.2%.The Karnofksy score improved in 42 cases.The toxicity reactions mostly included myelosuppression,followed by gastrointestinal mucosal lesions,nausea,vomiting and diarrhoea.CONCLUSION:Neoadjuvant chemotherapy consisting of docetaxel combined with oxaliplatin and fluorouracil is effective for stageⅢ/Ⅳgastric cancer.However,the treatment is associated with a high incidence of bone marrow suppression,which should be managed clinically.展开更多
The variation of toxic pollutants emission during a feeding cycle was examined by field monitoring from a batch feeding updraft fixed bed gasifier for disposing rural domestic solid waste. Results showed that the cont...The variation of toxic pollutants emission during a feeding cycle was examined by field monitoring from a batch feeding updraft fixed bed gasifier for disposing rural domestic solid waste. Results showed that the content of oxygen in flue gas gradually increased, while SO_2 and HCl in flue gas decreased with time after feeding in a whole feeding cycle. Although large amount of CO was produced during the gasifying, low CO content in flue gas could be obtained after the heat treatment with an electric heating device. The distribution characteristics of dioxin congeners in flue gas indicted the re-synthesis of dioxins after flue gas heating, and the increase of oxygen promoted the synthesis of dioxins. The emission content of dioxins could meet the standard(0.1 ng I-TEQ·m^(-3),GB18458-2014) of China when the oxygen content was controlled below 8.3%. Hence, for a batch feeding gasifier,low oxygen condition should be offered by reducing air intake at the later stage of feeding cycle in order to decrease the re-synthesis of dioxins after the flue gas heating.展开更多
By incorporating two different fracture mechanisms and salient unilateral effects in rock materials,we propose a thermomechanical phase-field model to capture thermally induced fracture and shear heating in the proces...By incorporating two different fracture mechanisms and salient unilateral effects in rock materials,we propose a thermomechanical phase-field model to capture thermally induced fracture and shear heating in the process of rock failure.The heat conduction equation is derived,from which the plastic dissipation is treated as a heat source.We then ascertain the effect of the non-associated plastic flow on frictional dissipation and show how it improves the predictive capability of the proposed model.Taking advantage of the multiscale analysis,we propose a phase-field-dependent thermal conductivity with considering the unilateral effect of fracture.After proposing a robust algorithm for solving involved three-field coupling and damage-plasticity coupling problems,we present three numerical examples to illustrate the abilities of our proposed model in capturing various thermo-mechanically coupled behaviors.展开更多
Accumulating evidence suggests that C-type lectin-like receptor-2(CLEC-2)plays an important role in atherothrombosis.In this case-control study,we investigated the association between CLEC-2 and incidence of coronary ...Accumulating evidence suggests that C-type lectin-like receptor-2(CLEC-2)plays an important role in atherothrombosis.In this case-control study,we investigated the association between CLEC-2 and incidence of coronary artery disease(CAD).A total of 216 patients,including 14 cases of stable angina pectoris(SAP,non-ACS)and 202 cases of acute coronary syndrome(ACS),and 89 non-CAD control subjects were enrolled.Plasma levels of soluble CLEC-2(sCLEC-2)were measured using the enzyme-linked immunosorbent assay(ELISA).Compared with the control group(65.69(55.36–143.22)pg/mL),the plasma levels of sCLEC-2 were significantly increased in patients with CAD(133.67(88.76–220.09)pg/mL)and ACS(134.16(88.88–225.81)pg/mL).The multivariate adjusted odds ratios(95%confidence interval)of CAD reached 2.01(1.52–2.66)(Ptrend<0.001)for each 1-quartile increase in sCLEC-2.Restricted cubic splines showed a positive dose-response association between sCLEC2 and CAD incidence(Plinearity<0.001).The addition of sCLEC-2 to conventional risk factors improved the C statistic(0.821 vs.0.761,P=0.004)and reclassification ability(net reclassification improvement:57.45%,P<0.001;integrated discrimination improvement:8.27%,P<0.001)for CAD.In conclusion,high plasma sCLEC-2 is independently associated with CAD risk,and the prognostic value of sCLEC-2 may be evaluated in future prospective studies.展开更多
Pollution discharge disturbs the natural functions of water systems. The environmental microbial com-munity composition and diversity are sensitive key indicators to the impact of water pol utant on the microbial ecol...Pollution discharge disturbs the natural functions of water systems. The environmental microbial com-munity composition and diversity are sensitive key indicators to the impact of water pol utant on the microbial ecology system over time. It is meaningful to develop a way to identify the microbial diversity related to heavy metal effects in evaluating river pol ution. Water and sediment samples were col ected from eight sections along the Tiaozi River where wastewater and sewage were discharged from Siping City in northeastern China. The main pollutants contents and microbial communities were analyzed. As the primary metal pol utants, zinc （Zn） and arsenic （As） were recorded at the maximum concentrations of 420 and 5.72 μg/L in the water, and 1704 and 1.92 mg/kg in the sediment, re-spectively. These pollutants posed a threat to the microbial community diversity as only a few species of bacteria and eukaryotes with strong resistance were detected through denaturing gradient gel electrophoresis （DGGE）. Acineto-bacter johnsoni , Clostridium cel ulovorans, and Trichococcus pasteuri were the dominant bacteria in the severely pol uted areas. The massive reproduction of Limnodrilus hoffmeisteri almost depleted the dissolved oxygen （DO） and resulted in the decline of the aerobic bacteria. It was noted that the pollution reduced the microbial diversity but the L. hoffmeisteri mass increased as the dominant community, which led to the overconsuming of DO and anaerobic stinking water bodies. Water quality, concentrations of heavy metals, and the spatial distribution of microbial popula-tions have obvious consistencies, which mean that the heavy metals in the river pose a serious stress on the microorganisms.展开更多
Many monoclonal antibodies(mAbs)have been extensively used in the clinic,such as rituximab to treat lymphoma.However,resistance and non-responsiveness to mAb treatment have been challenging for this line of therapy.Co...Many monoclonal antibodies(mAbs)have been extensively used in the clinic,such as rituximab to treat lymphoma.However,resistance and non-responsiveness to mAb treatment have been challenging for this line of therapy.Complement is one of the main mediators of antibody-based cancer therapy via the complement-dependent cytolysis(CDC)effect.CD59 plays a critical role in resistance to mAbs through the CDC effect.In this paper,we attempted to investigate whether the novel CD59 inhibitor,recombinant ILYd4,was effective in enhancing the rituximab-mediated CDC effect on rituximab-sensitive RL-7 lymphoma cells and rituximab-induced resistant RR51.2 cells.Meanwhile,the CDC effects,which were mediated by rituximab and anti-CD24 mAb,on the refractory multiple myeloma(MM)cell line ARH-77 and the solid tumor osteosarcoma cell line Saos-2,were respectively investigated.We found that rILYd4 rendered the refractory cells sensitive to the mAb-mediated CDC effect and that rILYd4 exhibited a synergistic effect with the mAb that resulted in tumor cells lysis.This effect on tumor cell lysis was apparent on both hematological tumors and solid tumors.Therefore,rILYd4 may serve as an adjuvant for mAb mediated-tumor immunotherapy.展开更多
Novel furoxan-based nitric oxide-releasing derivatives 6a-p of hydroxylcinnamic acids were synthesized by coupling the carboxyl group of hydroxylcinnamic acids with furoxan through various alkylol amines.Compounds 6a,...Novel furoxan-based nitric oxide-releasing derivatives 6a-p of hydroxylcinnamic acids were synthesized by coupling the carboxyl group of hydroxylcinnamic acids with furoxan through various alkylol amines.Compounds 6a,e-i and m-p displayed more potent anti-tumor activities superior to control 5-fluorouracil（5-FU） in most cancer cells tested.Furthermore,6f could selectively inhibit tumor cells,but not non-tumor cell proliferation.This inhibition was attributed to high levels of NO released in cancer cells and potentially synergistic effect of NO donor moieties and the bioactivity of hydroxylcinnamic acids.展开更多
Novel histone deacetylase （HDAC） inhibitors 9a-1 were designed and synthesized by coupling the carboxyl group of salicylic acid （SA） with N-hydroxycinnamamides through various alkylol amines, and their in vitro bi...Novel histone deacetylase （HDAC） inhibitors 9a-1 were designed and synthesized by coupling the carboxyl group of salicylic acid （SA） with N-hydroxycinnamamides through various alkylol amines, and their in vitro biological activities were evaluated. The N-hydroxycinnamamide/SA hybrids 9b-f and 9h showed good to moderate anti-tumor activities. Notably, compound 9e had a greater potency, comparable to vorinostat （SAHA）, in human colon carcinoma cells, which was probably, or at least partially, attributable to the positive effects of the chain length noted in allojlol amines. Furthermore, the HDAC inhibitory activities of 9e against Hela cell nuclear were also similar to that of vorinostat （SAHA）, while the tested compounds 9c-f did not exhibit any isoform selectivity in the inhibition of HDACs. In addition, compound 9e could selectively inhibit tumor cells, but not inhibit non-tumor cell proliferation in vitro. Our findings suggest that the N-hydroxycinnamamide/SA hybrids may hold significant promise as therapeutic a^ents for the intervention of human cancers.展开更多
基金supported by the Natural Science Research Project of Anhui Province University, No.2023AH040394 (to TY)Hefei Comprehensive National Science Center Leading Medicine and Frontier Technology Research Institute Project, No.2023IHM01073 (to TY)the Natural Science Foundation of Anhui Province, Nos.2308085QH258 (to JW), 2008085MH246 (to TY)。
文摘Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.
基金supported by grants from the National Natural Science Foundation of China(81770824,81270239)。
文摘Background:Abnormal myocardial voltage-gated sodium channel 1.5(Nav1.5)expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion(I/R).Protein inhibitor of activated STAT Y(PIASy)-mediated caveolin-3(Cav-3)small ubiquitin-related modifier(SUMO)modification affects Cav-3 binding to the Nav1.5.PIASy activity is increased after myocardial I/R,but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias.Methods:Using recombinant adeno-associated virus subtype 9(AAV9),rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA(shRNA).After two weeks,rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias.Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements.Results:PIASy was upregulated by I/R(P<0.01),with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density(P<0.01).AAV9-PIASy shRNA intraventricular injection into the rat heart down-regulated PIASy after I/R,at both mRNA and protein levels(P<0.05 vs.Scramble-shRNA+I/R group),decreased SUMO-modified Cav-3 levels,enhanced Cav-3 binding to Nav1.5,and prevented I/R-induced decrease of Nav1.5 and Cav-3co-localization in the intercalated disc and lateral membrane.PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias,which was reflected by a modest decrease in the duration of ventricular fibrillation(VF;P<0.05 vs.Scramble-shRNA+I/R group)and a significantly reduced arrhythmia score(P<0.01 vs.Scramble-shRNA+I/R group).The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia(VT),sustained VT and VF,especially at the time 5–10 min after ischemia(P<0.05 vs.Scramble-shRNA+IR group).Using in vitro human embryonic kidney 293 T(HEK293T)cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation(H/R),we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R.Mutation of SUMO consensus lysine sites in Cav-3(K38R or K144R)altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells.Conclusions:I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias.Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes,and subsequent ventricular arrhythmias in rats.PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.
文摘AIM:To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stageⅢ/Ⅳgastric cancer.METHODS:A total of 53 stageⅢ/Ⅳgastric cancer patients were enrolled into the study and treated with neoadjuvant chemotherapy.Two of the cases were excluded.The program was as follows:75 mg/m2docetaxel and 85 mg/m2 oxaliplatin on day 1 and 1500mg/m2 fluorouracil on days 1 to 3 for three weeks.RESULTS:The tumour changes,postoperative remission rate,changes in the symptoms and adverse reactions were observed.The overall clinical efficacy(com-plete remission+partial remission)of the neoadjuvant chemotherapy was 62.7%.R0 radical resection was performed on 60.8%of the patients,with a remission rate(pathological complete response+pathological subtotal response+pathological partial response)of74.2%.The Karnofksy score improved in 42 cases.The toxicity reactions mostly included myelosuppression,followed by gastrointestinal mucosal lesions,nausea,vomiting and diarrhoea.CONCLUSION:Neoadjuvant chemotherapy consisting of docetaxel combined with oxaliplatin and fluorouracil is effective for stageⅢ/Ⅳgastric cancer.However,the treatment is associated with a high incidence of bone marrow suppression,which should be managed clinically.
基金Supported by the Science and Technology Planning Project of Guangdong Province,China(2013B090600134)the National Natural Science Foundation of China(51608223)the Fund for Basic Scientific Research Business of Central Institutes of Environmental Protection(PM-zx 703-201602-050)
文摘The variation of toxic pollutants emission during a feeding cycle was examined by field monitoring from a batch feeding updraft fixed bed gasifier for disposing rural domestic solid waste. Results showed that the content of oxygen in flue gas gradually increased, while SO_2 and HCl in flue gas decreased with time after feeding in a whole feeding cycle. Although large amount of CO was produced during the gasifying, low CO content in flue gas could be obtained after the heat treatment with an electric heating device. The distribution characteristics of dioxin congeners in flue gas indicted the re-synthesis of dioxins after flue gas heating, and the increase of oxygen promoted the synthesis of dioxins. The emission content of dioxins could meet the standard(0.1 ng I-TEQ·m^(-3),GB18458-2014) of China when the oxygen content was controlled below 8.3%. Hence, for a batch feeding gasifier,low oxygen condition should be offered by reducing air intake at the later stage of feeding cycle in order to decrease the re-synthesis of dioxins after the flue gas heating.
基金funding provided by the National Natural Science Foundation of China(No.12202137)TY's contribution is funded by the China and Germany Postdoctoral Exchange Program(Grant No.ZD202137).The first author(TY)would like to express his gratitude to Prof.Keita Yoshioka for reviewing this manuscript and for his invaluable feedback.
文摘By incorporating two different fracture mechanisms and salient unilateral effects in rock materials,we propose a thermomechanical phase-field model to capture thermally induced fracture and shear heating in the process of rock failure.The heat conduction equation is derived,from which the plastic dissipation is treated as a heat source.We then ascertain the effect of the non-associated plastic flow on frictional dissipation and show how it improves the predictive capability of the proposed model.Taking advantage of the multiscale analysis,we propose a phase-field-dependent thermal conductivity with considering the unilateral effect of fracture.After proposing a robust algorithm for solving involved three-field coupling and damage-plasticity coupling problems,we present three numerical examples to illustrate the abilities of our proposed model in capturing various thermo-mechanically coupled behaviors.
基金supported by the National Key Research and Development Program(2022YFC2503400)the Fundamental Research Funds for the Central Universities(2019PT350005)+4 种基金the National Natural Science Foundation of China(81970444)the Beijing Municipal Science and Technology Project(Z201100005420030)the National High Level Talents Special Support Plan(2020-RSW02)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-065)the Sanming Project of Medicine in Shenzhen(SZSM202011013)。
基金supported by grants from the National Natural Science Foundation of China(Nos.81870325,81620108001,and 91739302 to Li Zhu)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China and Suzhou Key laboratory of Thrombosis and Vascular Diseases(to Li Zhu)+1 种基金the Suzhou Science and Technology Project Foundation(No.SYS201721 to Li Xiang)the Young Investigator Pre-research Foundation of the Second Affiliated Hospital of Soochow University(No.SDFEYQN1717 to Tao You).
文摘Accumulating evidence suggests that C-type lectin-like receptor-2(CLEC-2)plays an important role in atherothrombosis.In this case-control study,we investigated the association between CLEC-2 and incidence of coronary artery disease(CAD).A total of 216 patients,including 14 cases of stable angina pectoris(SAP,non-ACS)and 202 cases of acute coronary syndrome(ACS),and 89 non-CAD control subjects were enrolled.Plasma levels of soluble CLEC-2(sCLEC-2)were measured using the enzyme-linked immunosorbent assay(ELISA).Compared with the control group(65.69(55.36–143.22)pg/mL),the plasma levels of sCLEC-2 were significantly increased in patients with CAD(133.67(88.76–220.09)pg/mL)and ACS(134.16(88.88–225.81)pg/mL).The multivariate adjusted odds ratios(95%confidence interval)of CAD reached 2.01(1.52–2.66)(Ptrend<0.001)for each 1-quartile increase in sCLEC-2.Restricted cubic splines showed a positive dose-response association between sCLEC2 and CAD incidence(Plinearity<0.001).The addition of sCLEC-2 to conventional risk factors improved the C statistic(0.821 vs.0.761,P=0.004)and reclassification ability(net reclassification improvement:57.45%,P<0.001;integrated discrimination improvement:8.27%,P<0.001)for CAD.In conclusion,high plasma sCLEC-2 is independently associated with CAD risk,and the prognostic value of sCLEC-2 may be evaluated in future prospective studies.
基金Project supported by the National Science and Technology Majo Project of China(Nos.2008ZX07208-005 and 2012ZX07202-003)
文摘Pollution discharge disturbs the natural functions of water systems. The environmental microbial com-munity composition and diversity are sensitive key indicators to the impact of water pol utant on the microbial ecology system over time. It is meaningful to develop a way to identify the microbial diversity related to heavy metal effects in evaluating river pol ution. Water and sediment samples were col ected from eight sections along the Tiaozi River where wastewater and sewage were discharged from Siping City in northeastern China. The main pollutants contents and microbial communities were analyzed. As the primary metal pol utants, zinc （Zn） and arsenic （As） were recorded at the maximum concentrations of 420 and 5.72 μg/L in the water, and 1704 and 1.92 mg/kg in the sediment, re-spectively. These pollutants posed a threat to the microbial community diversity as only a few species of bacteria and eukaryotes with strong resistance were detected through denaturing gradient gel electrophoresis （DGGE）. Acineto-bacter johnsoni , Clostridium cel ulovorans, and Trichococcus pasteuri were the dominant bacteria in the severely pol uted areas. The massive reproduction of Limnodrilus hoffmeisteri almost depleted the dissolved oxygen （DO） and resulted in the decline of the aerobic bacteria. It was noted that the pollution reduced the microbial diversity but the L. hoffmeisteri mass increased as the dominant community, which led to the overconsuming of DO and anaerobic stinking water bodies. Water quality, concentrations of heavy metals, and the spatial distribution of microbial popula-tions have obvious consistencies, which mean that the heavy metals in the river pose a serious stress on the microorganisms.
基金the US NIH through grant RO1 AI061174(XBQ)grant R21 CA141324(XBQ)the Harvard Technology Development Accelerator Fund(XBQ),and the Fund of the China Scholarship Council No.2008638052(TY).
文摘Many monoclonal antibodies(mAbs)have been extensively used in the clinic,such as rituximab to treat lymphoma.However,resistance and non-responsiveness to mAb treatment have been challenging for this line of therapy.Complement is one of the main mediators of antibody-based cancer therapy via the complement-dependent cytolysis(CDC)effect.CD59 plays a critical role in resistance to mAbs through the CDC effect.In this paper,we attempted to investigate whether the novel CD59 inhibitor,recombinant ILYd4,was effective in enhancing the rituximab-mediated CDC effect on rituximab-sensitive RL-7 lymphoma cells and rituximab-induced resistant RR51.2 cells.Meanwhile,the CDC effects,which were mediated by rituximab and anti-CD24 mAb,on the refractory multiple myeloma(MM)cell line ARH-77 and the solid tumor osteosarcoma cell line Saos-2,were respectively investigated.We found that rILYd4 rendered the refractory cells sensitive to the mAb-mediated CDC effect and that rILYd4 exhibited a synergistic effect with the mAb that resulted in tumor cells lysis.This effect on tumor cell lysis was apparent on both hematological tumors and solid tumors.Therefore,rILYd4 may serve as an adjuvant for mAb mediated-tumor immunotherapy.
文摘Novel furoxan-based nitric oxide-releasing derivatives 6a-p of hydroxylcinnamic acids were synthesized by coupling the carboxyl group of hydroxylcinnamic acids with furoxan through various alkylol amines.Compounds 6a,e-i and m-p displayed more potent anti-tumor activities superior to control 5-fluorouracil（5-FU） in most cancer cells tested.Furthermore,6f could selectively inhibit tumor cells,but not non-tumor cell proliferation.This inhibition was attributed to high levels of NO released in cancer cells and potentially synergistic effect of NO donor moieties and the bioactivity of hydroxylcinnamic acids.
文摘Novel histone deacetylase （HDAC） inhibitors 9a-1 were designed and synthesized by coupling the carboxyl group of salicylic acid （SA） with N-hydroxycinnamamides through various alkylol amines, and their in vitro biological activities were evaluated. The N-hydroxycinnamamide/SA hybrids 9b-f and 9h showed good to moderate anti-tumor activities. Notably, compound 9e had a greater potency, comparable to vorinostat （SAHA）, in human colon carcinoma cells, which was probably, or at least partially, attributable to the positive effects of the chain length noted in allojlol amines. Furthermore, the HDAC inhibitory activities of 9e against Hela cell nuclear were also similar to that of vorinostat （SAHA）, while the tested compounds 9c-f did not exhibit any isoform selectivity in the inhibition of HDACs. In addition, compound 9e could selectively inhibit tumor cells, but not inhibit non-tumor cell proliferation in vitro. Our findings suggest that the N-hydroxycinnamamide/SA hybrids may hold significant promise as therapeutic a^ents for the intervention of human cancers.
