Objective Non-small cell lung cancer(NSCLC)is a leading cause of cancer-associated mortality.This study aimed to investigate the role of checkpoint kinase 1(CHEK1)in NSCLC progression and its regulatory relationship w...Objective Non-small cell lung cancer(NSCLC)is a leading cause of cancer-associated mortality.This study aimed to investigate the role of checkpoint kinase 1(CHEK1)in NSCLC progression and its regulatory relationship with forkhead box protein M1(FOXM1).Methods Transwell assays were used to evaluate the migration and invasion capabilities of NSCLC cells with either CHEK1 overexpression or knockdown.The expression of epithelial−mesenchymal transition(EMT)markers in NSCLC cells under CHEK1 overexpression or knockdown conditions was analyzed via Western blotting.Proliferative capacity was assessed using CCK-8 assays in NSCLC cells with modulated CHEK1 expression.Additionally,real-time quantitative PCR was employed to measure CHEK1 and FOXM1 expression levels in NSCLC tissues.The effects of CHEK1 knockdown on tumor growth were further validated in animal models.The binding of FOXM1 to the CHEK1 promoter region was examined using dual-luciferase reporter assays and chromatin immunoprecipitation(ChIP)assays.Results FOXM1 and CHEK1 were upregulated in NSCLC tissues.CHEK1 overexpression promoted NSCLC cell proliferation,while its knockdown suppressed proliferation,inhibited EMT,and reduced tumor growth in vivo.FOXM1 was shown to directly bind to CHEK1 promoter,thereby upregulating CHEK1 expression.Conclusion CHEK1 promotes NSCLC cell proliferation and tumor growth,and its expression is regulated by FOXM1.These findings suggest CHEK1 and FOXM1 are potential therapeutic targets for NSCLC treatment.展开更多
Diabetic patients often have problems such as residual tumor and wound infection after tumor resection,causing severe clinical problems.It is urgent to develop effective therapies to reach oncotherapy/antiinfection/pr...Diabetic patients often have problems such as residual tumor and wound infection after tumor resection,causing severe clinical problems.It is urgent to develop effective therapies to reach oncotherapy/antiinfection/promotion of wound healing combined treatment.Herein,we propose CS/MnO_(2)-GO_x (CMGO_x)nanocatalysts for the specific catalytic generation of ~·OH to inhibit tumors and bacteria in a hyperglycemic environment.The good biocompatible chitosan (CS),as a carrier for the catalyst,exhibits excellent antibacterial effect as well as promotes wound healing.Glucose oxidase (GO_x) is loaded on the surface of CS nanoparticles to generate H_(2)O_(2) and gluconic acid by consuming glucose (starvation therapy,ST) and O_(2).The MnO_(2) depletes glutathione (GSH) to produce Mn^(2+),amplifying oxidative stress and further promoting the activity of Mn^(2+)-mediated Fenton-like reaction to produce~·OH (chemodynamic therapy,CDT)in weak acidic environment.Moreover,the produced gluconic acid lowers the p H of the environment,enhancing chemodynamic therapy (ECDT).The tumor cells and bacteria are efficiently eliminated by the synergistic effect of ST and ECDT.The MnO_(2) nanoparticles at neutral environment decomposes H_(2)O_(2) into O_(2),which cooperate with CS to promote healing.The self-enhanced cascade reaction of CMGO_x in situ exhibits excellent effects of antitumor/antibacterial therapy and promotion of wound healing,offering a promising integrated treatment for diabetic patients after tumor surgical resection.展开更多
The effective elimination of aromatic compounds from wastewater is imperative for safeguarding the ecological environment.Bioelectrochemical processes that combine cathodic reduction and anodic oxidation represent a p...The effective elimination of aromatic compounds from wastewater is imperative for safeguarding the ecological environment.Bioelectrochemical processes that combine cathodic reduction and anodic oxidation represent a promising approach for the biomineralization of aromatic compounds.However,conventional direct current bioelectrochemical methods have intrinsic limitations.In this study,a low-frequency and low-voltage alternating current(LFV-AC)-driven bioelectrode offering periodic in situ coupling of reduction and oxidation processes was developed for the biomineralization of aromatic compounds,as exemplified by the degradation of alizarin yellow R(AYR).LFV-AC stimulated biofilm demonstrated efficient bidirectional electron transfer and oxidation–reduction bifunctionality,considerably boosting AYR reduction(63.07%±1.91%)and subsequent mineralization of intermediate products(98.63%±0.37%).LFV-AC stimulation facilitated the assembly of a collaborative microbiome dedicated to AYR metabolism,characterized by an increased abundance of functional consortia proficient in azo dye reduction(Stenotrophomonas and Bradyrhizobium),aromatic intermediate oxidation(Sphingopyxis and Sphingomonas),and electron transfer(Geobacter and Pseudomonas).The collaborative microbiome demonstrated a notable enrichment of functional genes encoding azo-and nitro-reductases,catechol oxygenases,and redox mediator proteins.These findings highlight the effectiveness of LFV-AC stimulation in boosting azo dye biomineralization,offering a novel and sustainable approach for the efficient removal of refractory organic pollutants from wastewater.展开更多
背景与目的探讨不同部位的肺叶切除术后患者肺容积减少与患者肺功能损害程度的相关性。方法本研究共纳入苏州大学附属第一医院2019年1月-2020年7月行胸腔镜肺叶切除术的131例患者(包括左肺上叶,左肺下叶,右肺上叶,右肺中叶,右肺下叶切除...背景与目的探讨不同部位的肺叶切除术后患者肺容积减少与患者肺功能损害程度的相关性。方法本研究共纳入苏州大学附属第一医院2019年1月-2020年7月行胸腔镜肺叶切除术的131例患者(包括左肺上叶,左肺下叶,右肺上叶,右肺中叶,右肺下叶切除术;其中男性72例,女性59例)。为了比较患者术后肺功能与术前肺功能的差异,分别于术前7天和术后3个月、6个月及1年记录患者的肺功能测量值。采用1秒用力呼气量(forced expiratory volume in 1second,FEV_(1))作为肺功能变化的主要评估参数。采用Mimics Research 19.0软件计算出患者的原始肺容积,各阶段存留的肺容积。分析患者肺容积在上述时间节点与患者肺功能变化的相关性。结果术后患者FEV1较术前降低,下降程度与肺叶的切除体积呈正相关(其中左下肺下降较为明显)。值得注意的是,患者的肺功能降低程度在术后3个月、6个月与1年的差异无统计学意义。结论肺叶切除术后肺组织的容积减少是患者肺功能减少的主要原因,以左肺下叶表现为著,最早可选定术后3个月作为肺叶切除患者残留肺功能的评估节点。展开更多
BACKGROUND Pancreatic fistula is one of the most serious complications after pancreatoduodenectomy for treating any lesions at the pancreatic head. For years, surgeons have tried various methods to reduce its incidenc...BACKGROUND Pancreatic fistula is one of the most serious complications after pancreatoduodenectomy for treating any lesions at the pancreatic head. For years, surgeons have tried various methods to reduce its incidence. AIM To investigate and emphasize the clinical outcomes of Blumgart anastomosis compared with traditional anastomosis in reducing postoperative pancreatic fistula. METHODS In this observational study, a retrospective analysis of 291 patients who underwent pancreatoduodenectomy, including Blumgart anastomosis (201 patients) and traditional embedded pancreaticojejunostomy (90 patients), was performed in our hospital. The preoperative and perioperative courses and longterm follow-up status were analyzed to compare the advantages and disadvantages of the two methods. Moreover, 291 patients were then separated by the severity of postoperative pancreatic fistula, and two methods of pancreaticojejunostomy were compared to detect the features of different anastomosis. Six experienced surgeons were involved and all of them were proficient in both surgical techniques.RESULTS The characteristics of the patients in the two groups showed no significant differences, nor the preoperative information and pathological diagnoses. The operative time was significantly shorter in the Blumgart group (343.5 ± 23.0 vs 450.0 ± 40.1 min, P = 0.028), as well as the duration of pancreaticojejunostomy drainage tube placement and postoperative hospital stay (12.7 ± 0.9 d vs 17.4 ± 1.8 d, P = 0.031;and 21.9 ± 1.3 d vs 28.9 ± 1.3 d, P = 0.020, respectively). The overall complications after surgery were much less in the Blumgart group than in the embedded group (11.9% vs 26.7%, P = 0.002). Patients who underwent Blumgart anastomosis would suffer less from severe pancreatic fistula (71.9% vs 50.0%, P = 0.006), and this pancreaticojejunostomy procedure did not have worse influences on long-term complications and life quality. Thus, Blumgart anastomosis is a feasible pancreaticojejunostomy procedure in pancreatoduodenectomy surgery. It is safe in causing less postoperative complications, especially pancreatic fistula, and thus shortens the hospitalization duration. CONCLUSION Surgical method should be a key factor in reducing pancreatic fistula, and Blumgart anastomosis needs further promotion.展开更多
Purpose： To extract protein, decrease the cellulose and facilitate the digestion and absorption of brewers＇ spent grain by animal. Topic： Discuss and optimize the hydrolysis conditions of the combined enzymatic hyd...Purpose： To extract protein, decrease the cellulose and facilitate the digestion and absorption of brewers＇ spent grain by animal. Topic： Discuss and optimize the hydrolysis conditions of the combined enzymatic hydrolysis by Novozymes. Method： The fresh brewers＇ spent grain was firstly dried, smashed and sifted. Then as indicators of the protein extraction rate in the enzyme solution and the content of cellulose in the index, the parameters of enzymatic hydrolysis, such as the solid-liquid ratio, reaction temperature, pH, enzyme dosage and reaction time, were investigated in detailed. After hydrolysis, the brewers＇ spent grain was put in the boiling water bath for inactivation for 15 minutes, and centrifuged, the supernatants were volume to 100 mL and the protein content was measured. After the precipitate was dried, the cellulose content was also measured. Achievements： The optimized conditions were with temperature of 50 ℃, pH 6.5, enzyme amount of 30 mg for Novozymes enzyme and 2.5 h for reaction time. Under these conditions, the protein extraction rate in the enzyme reaction reached 41.82%, and the cellulose content reached 13.90%, the degradation rate of cellulose was 18.86%.展开更多
Advanced atherosclerotic lesions and vascular calcification substantially increase the risk of cardiovascular events.However,effective strategies for preventing or treating advanced atherosclerosis and calcification a...Advanced atherosclerotic lesions and vascular calcification substantially increase the risk of cardiovascular events.However,effective strategies for preventing or treating advanced atherosclerosis and calcification are currently lacking.This study investigated the efficacy of DT-109(Gly-Gly-Leu)in attenuating atherosclerosis and calcification in nonhuman primates,exploring its broader therapeutic potential.In this study,twenty male cynomolgus monkeys were administered a cholesterol-rich diet ad libitum for 10 months.Then,the animals were treated either orally with DT-109(150 mg/kg/day)or a vehicle(H2O)for 5 months while continuing on the same diet.Plasma lipid levels were measured monthly and at the end of the experiment,pathological examinations of the aortas and coronary arteries and RNA sequencing of the coronary arteries were performed.To explore possible molecular mechanisms,the effects of DT-109 on smooth muscle cells(SMCs)were examined in vitro.We found that DT-109 administration significantly suppressed atherosclerotic lesion formation in both the aorta and coronary arteries.Pathological examinations revealed that DT-109 treatment reduced lesional macrophage content and calcification.RNA sequencing analysis showed that DT-109 treatment significantly downregulated the pro-inflammatory factors NLRP3,AIM2,and CASP1,the oxidative stress factors NCF2 and NCF4,and the osteogenic factors RUNX2,COL1A1,MMP2,and MMP9,while simultaneously upregulating the expression of the SMCs contraction markers ACTA2,CNN1,and TAGLN.Furthermore,DT-109 inhibited SMC calcification and NLRP3 inflammasome activation in vitro.These results demonstrate that DT-109 effectively suppresses both atherosclerosis and calcification.These findings,in conjunction with insights from our previous studies,position DT-109 as a novel multifaceted therapeutic agent for cardiovascular diseases.展开更多
基金funded by the Suqian Science and Technology Program Project(No.K202008).
文摘Objective Non-small cell lung cancer(NSCLC)is a leading cause of cancer-associated mortality.This study aimed to investigate the role of checkpoint kinase 1(CHEK1)in NSCLC progression and its regulatory relationship with forkhead box protein M1(FOXM1).Methods Transwell assays were used to evaluate the migration and invasion capabilities of NSCLC cells with either CHEK1 overexpression or knockdown.The expression of epithelial−mesenchymal transition(EMT)markers in NSCLC cells under CHEK1 overexpression or knockdown conditions was analyzed via Western blotting.Proliferative capacity was assessed using CCK-8 assays in NSCLC cells with modulated CHEK1 expression.Additionally,real-time quantitative PCR was employed to measure CHEK1 and FOXM1 expression levels in NSCLC tissues.The effects of CHEK1 knockdown on tumor growth were further validated in animal models.The binding of FOXM1 to the CHEK1 promoter region was examined using dual-luciferase reporter assays and chromatin immunoprecipitation(ChIP)assays.Results FOXM1 and CHEK1 were upregulated in NSCLC tissues.CHEK1 overexpression promoted NSCLC cell proliferation,while its knockdown suppressed proliferation,inhibited EMT,and reduced tumor growth in vivo.FOXM1 was shown to directly bind to CHEK1 promoter,thereby upregulating CHEK1 expression.Conclusion CHEK1 promotes NSCLC cell proliferation and tumor growth,and its expression is regulated by FOXM1.These findings suggest CHEK1 and FOXM1 are potential therapeutic targets for NSCLC treatment.
基金supported by the Laboratory Animal Welfare and Ethics Committee of the Clinical Center of Shanghai First People's Hospital (No. 2020AWS0065)financially supported by the National Natural Science Foundation of China (Nos. 21978165, 92156020)+1 种基金Science and Technology Commission of Shanghai (No. 20DZ2255900)Class Ⅲ Peak Discipline of Shanghai—Materials Science and Engineering (High-Energy Beam Intelligent Processing and Green Manufacturing)。
文摘Diabetic patients often have problems such as residual tumor and wound infection after tumor resection,causing severe clinical problems.It is urgent to develop effective therapies to reach oncotherapy/antiinfection/promotion of wound healing combined treatment.Herein,we propose CS/MnO_(2)-GO_x (CMGO_x)nanocatalysts for the specific catalytic generation of ~·OH to inhibit tumors and bacteria in a hyperglycemic environment.The good biocompatible chitosan (CS),as a carrier for the catalyst,exhibits excellent antibacterial effect as well as promotes wound healing.Glucose oxidase (GO_x) is loaded on the surface of CS nanoparticles to generate H_(2)O_(2) and gluconic acid by consuming glucose (starvation therapy,ST) and O_(2).The MnO_(2) depletes glutathione (GSH) to produce Mn^(2+),amplifying oxidative stress and further promoting the activity of Mn^(2+)-mediated Fenton-like reaction to produce~·OH (chemodynamic therapy,CDT)in weak acidic environment.Moreover,the produced gluconic acid lowers the p H of the environment,enhancing chemodynamic therapy (ECDT).The tumor cells and bacteria are efficiently eliminated by the synergistic effect of ST and ECDT.The MnO_(2) nanoparticles at neutral environment decomposes H_(2)O_(2) into O_(2),which cooperate with CS to promote healing.The self-enhanced cascade reaction of CMGO_x in situ exhibits excellent effects of antitumor/antibacterial therapy and promotion of wound healing,offering a promising integrated treatment for diabetic patients after tumor surgical resection.
基金supported by the National Natural Science Foundation of China(52170054,51608467,and 52200202)the“Qing Lan Project”of Colleges and Universities in Jiangsu Province。
文摘The effective elimination of aromatic compounds from wastewater is imperative for safeguarding the ecological environment.Bioelectrochemical processes that combine cathodic reduction and anodic oxidation represent a promising approach for the biomineralization of aromatic compounds.However,conventional direct current bioelectrochemical methods have intrinsic limitations.In this study,a low-frequency and low-voltage alternating current(LFV-AC)-driven bioelectrode offering periodic in situ coupling of reduction and oxidation processes was developed for the biomineralization of aromatic compounds,as exemplified by the degradation of alizarin yellow R(AYR).LFV-AC stimulated biofilm demonstrated efficient bidirectional electron transfer and oxidation–reduction bifunctionality,considerably boosting AYR reduction(63.07%±1.91%)and subsequent mineralization of intermediate products(98.63%±0.37%).LFV-AC stimulation facilitated the assembly of a collaborative microbiome dedicated to AYR metabolism,characterized by an increased abundance of functional consortia proficient in azo dye reduction(Stenotrophomonas and Bradyrhizobium),aromatic intermediate oxidation(Sphingopyxis and Sphingomonas),and electron transfer(Geobacter and Pseudomonas).The collaborative microbiome demonstrated a notable enrichment of functional genes encoding azo-and nitro-reductases,catechol oxygenases,and redox mediator proteins.These findings highlight the effectiveness of LFV-AC stimulation in boosting azo dye biomineralization,offering a novel and sustainable approach for the efficient removal of refractory organic pollutants from wastewater.
文摘背景与目的探讨不同部位的肺叶切除术后患者肺容积减少与患者肺功能损害程度的相关性。方法本研究共纳入苏州大学附属第一医院2019年1月-2020年7月行胸腔镜肺叶切除术的131例患者(包括左肺上叶,左肺下叶,右肺上叶,右肺中叶,右肺下叶切除术;其中男性72例,女性59例)。为了比较患者术后肺功能与术前肺功能的差异,分别于术前7天和术后3个月、6个月及1年记录患者的肺功能测量值。采用1秒用力呼气量(forced expiratory volume in 1second,FEV_(1))作为肺功能变化的主要评估参数。采用Mimics Research 19.0软件计算出患者的原始肺容积,各阶段存留的肺容积。分析患者肺容积在上述时间节点与患者肺功能变化的相关性。结果术后患者FEV1较术前降低,下降程度与肺叶的切除体积呈正相关(其中左下肺下降较为明显)。值得注意的是,患者的肺功能降低程度在术后3个月、6个月与1年的差异无统计学意义。结论肺叶切除术后肺组织的容积减少是患者肺功能减少的主要原因,以左肺下叶表现为著,最早可选定术后3个月作为肺叶切除患者残留肺功能的评估节点。
文摘BACKGROUND Pancreatic fistula is one of the most serious complications after pancreatoduodenectomy for treating any lesions at the pancreatic head. For years, surgeons have tried various methods to reduce its incidence. AIM To investigate and emphasize the clinical outcomes of Blumgart anastomosis compared with traditional anastomosis in reducing postoperative pancreatic fistula. METHODS In this observational study, a retrospective analysis of 291 patients who underwent pancreatoduodenectomy, including Blumgart anastomosis (201 patients) and traditional embedded pancreaticojejunostomy (90 patients), was performed in our hospital. The preoperative and perioperative courses and longterm follow-up status were analyzed to compare the advantages and disadvantages of the two methods. Moreover, 291 patients were then separated by the severity of postoperative pancreatic fistula, and two methods of pancreaticojejunostomy were compared to detect the features of different anastomosis. Six experienced surgeons were involved and all of them were proficient in both surgical techniques.RESULTS The characteristics of the patients in the two groups showed no significant differences, nor the preoperative information and pathological diagnoses. The operative time was significantly shorter in the Blumgart group (343.5 ± 23.0 vs 450.0 ± 40.1 min, P = 0.028), as well as the duration of pancreaticojejunostomy drainage tube placement and postoperative hospital stay (12.7 ± 0.9 d vs 17.4 ± 1.8 d, P = 0.031;and 21.9 ± 1.3 d vs 28.9 ± 1.3 d, P = 0.020, respectively). The overall complications after surgery were much less in the Blumgart group than in the embedded group (11.9% vs 26.7%, P = 0.002). Patients who underwent Blumgart anastomosis would suffer less from severe pancreatic fistula (71.9% vs 50.0%, P = 0.006), and this pancreaticojejunostomy procedure did not have worse influences on long-term complications and life quality. Thus, Blumgart anastomosis is a feasible pancreaticojejunostomy procedure in pancreatoduodenectomy surgery. It is safe in causing less postoperative complications, especially pancreatic fistula, and thus shortens the hospitalization duration. CONCLUSION Surgical method should be a key factor in reducing pancreatic fistula, and Blumgart anastomosis needs further promotion.
文摘Purpose： To extract protein, decrease the cellulose and facilitate the digestion and absorption of brewers＇ spent grain by animal. Topic： Discuss and optimize the hydrolysis conditions of the combined enzymatic hydrolysis by Novozymes. Method： The fresh brewers＇ spent grain was firstly dried, smashed and sifted. Then as indicators of the protein extraction rate in the enzyme solution and the content of cellulose in the index, the parameters of enzymatic hydrolysis, such as the solid-liquid ratio, reaction temperature, pH, enzyme dosage and reaction time, were investigated in detailed. After hydrolysis, the brewers＇ spent grain was put in the boiling water bath for inactivation for 15 minutes, and centrifuged, the supernatants were volume to 100 mL and the protein content was measured. After the precipitate was dried, the cellulose content was also measured. Achievements： The optimized conditions were with temperature of 50 ℃, pH 6.5, enzyme amount of 30 mg for Novozymes enzyme and 2.5 h for reaction time. Under these conditions, the protein extraction rate in the enzyme reaction reached 41.82%, and the cellulose content reached 13.90%, the degradation rate of cellulose was 18.86%.
基金partially supported by the National Key R&D Program of China(No.2020YFA0803700)National Natural Science Foundation of China(No.81970425 and No.81941001)+6 种基金Natural Science Foundation of Shaanxi Province(No.2020PT-001)Innovation team program supported by Guangdong Province(2020KCXTD038)Guangdong Province Key Program of Discipline(2021ZDJS091)National Key Research and Development Program of China(2022YFA1105403)Science and Technology Planning Project of Guangdong Province(2021A1515110916)the Hong Kong-Macao Joint Research and Development Fund of Wuyi UniversityFrederick G.L.Huetwell Endowed Professor of Cardiovascular Medicine at University of Michigan(Y.E.C.).
文摘Advanced atherosclerotic lesions and vascular calcification substantially increase the risk of cardiovascular events.However,effective strategies for preventing or treating advanced atherosclerosis and calcification are currently lacking.This study investigated the efficacy of DT-109(Gly-Gly-Leu)in attenuating atherosclerosis and calcification in nonhuman primates,exploring its broader therapeutic potential.In this study,twenty male cynomolgus monkeys were administered a cholesterol-rich diet ad libitum for 10 months.Then,the animals were treated either orally with DT-109(150 mg/kg/day)or a vehicle(H2O)for 5 months while continuing on the same diet.Plasma lipid levels were measured monthly and at the end of the experiment,pathological examinations of the aortas and coronary arteries and RNA sequencing of the coronary arteries were performed.To explore possible molecular mechanisms,the effects of DT-109 on smooth muscle cells(SMCs)were examined in vitro.We found that DT-109 administration significantly suppressed atherosclerotic lesion formation in both the aorta and coronary arteries.Pathological examinations revealed that DT-109 treatment reduced lesional macrophage content and calcification.RNA sequencing analysis showed that DT-109 treatment significantly downregulated the pro-inflammatory factors NLRP3,AIM2,and CASP1,the oxidative stress factors NCF2 and NCF4,and the osteogenic factors RUNX2,COL1A1,MMP2,and MMP9,while simultaneously upregulating the expression of the SMCs contraction markers ACTA2,CNN1,and TAGLN.Furthermore,DT-109 inhibited SMC calcification and NLRP3 inflammasome activation in vitro.These results demonstrate that DT-109 effectively suppresses both atherosclerosis and calcification.These findings,in conjunction with insights from our previous studies,position DT-109 as a novel multifaceted therapeutic agent for cardiovascular diseases.
