Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients...Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients.Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions.For the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic cancer.Moreover,CD44 was found to interact with integrin a6b4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling cascades.Notably,we also demonstrated that the CD44–a6b4 complex can be delivered to the target region via the paracrine effects of exosomes.The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor metastasis.Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.展开更多
Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior(No. 8 p,No. 12 b/p, No. 13, and No. 14 v), and para-aortic(No. 16 a2, and No. 16 b1) lymph nodes(LNs) in subtotal gast...Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior(No. 8 p,No. 12 b/p, No. 13, and No. 14 v), and para-aortic(No. 16 a2, and No. 16 b1) lymph nodes(LNs) in subtotal gastrectomy for advanced gastric antral carcinoma.Methods: A total of 203 patients with advanced gastric cancer(GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled.Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses. The therapeutic value index(TVI) was calculate to evaluate the survival benefit of dissecting each LN station.Results: Of 102 patients with D2-plus lymphadenectomy, 21(20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy. After matching, the overall survival(OS) was significantly better in the D2-plus than the D2 group(P=0.030). In the multivariate survival analysis, D2-plus lymphadenectomy(hazard ratio, 0.516;P=0.006) was confirmed to significantly improve the survival rate. In the logistic regression analysis, p N stage [odds ratio(OR), 2.533;95% confidence interval(95% CI), 1.368-4.691;P=0.003] and extent of LNs metastasis(OR, 5.965;95% CI, 1.335-26.650;P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy. The TVI of patient with metastasis to LNs station was 7.1(No. 8p), 5.7(No. 12p), 5.1(No. 13), and 7.1(both No. 16a2 and No. 16b1), respectively.Conclusions: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16.展开更多
Modern diets,which often feature high levels of fat and charcoal-grilled meat,contribute to the pathogenesis of obesity and non-alcoholic fatty liver disease(NAFLD),resulting in liver cancer progression.Benzo(a)pyrene...Modern diets,which often feature high levels of fat and charcoal-grilled meat,contribute to the pathogenesis of obesity and non-alcoholic fatty liver disease(NAFLD),resulting in liver cancer progression.Benzo(a)pyrene(B[a]P)is a common environ-mental and foodborne pollutant found in smoke and fire-grilled foods,which can have an adverse effect on human health.Hepatocellular carcinoma(HCC)is the fifth leading cause of cancer and the second leading cause of cancer-related deaths worldwide.The epidemiological studies suggest that both environmental risk factors and chronic liver injury including NAFL are important for HCC development,but the precise mechanisms linking eating habits to hepato-carcinogenesis remain unclear.In the present study,we demonstrated that various miRNAs in B[a]P-exposed tumor cells contribute to tumor metastasis,among which miR-650 could be the most potent inducer.Furthermore,we found that the suppressor of cytokine signaling 3(SOCS3)is directly regulated by miR-650 and its suppression regulates the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3)cascade.Our findings reveal a possible adverse outcome pathway of SOCS3/JAK/STAT3 regulation in B[a]P-induced HCC progress.These results provide a better understanding of the adverse effects of chronic exposure to B[a]P on human health.展开更多
Fluorescence-based white-light-emitting diodes （WLEDs） were fabricated using blue GaN chips and green- and red-emitting CdSe/CdS/ZnS quantum dots （QDs）. The coordinate and color temperature of the WLEDs could be v...Fluorescence-based white-light-emitting diodes （WLEDs） were fabricated using blue GaN chips and green- and red-emitting CdSe/CdS/ZnS quantum dots （QDs）. The coordinate and color temperature of the WLEDs could be varied because of the size-tunable emission of CdSe QDs from 510 to 620 nm. Warm and cold white emissions were confirmed with the color temperature ranging from 4000 to 9000 K. Color coordinates were analyzed at different bias. The fast enhancement of blue emission resulted in the shift of color coordinates to the cold side. The stability of white emission during operation was analyzed; stable spectra were achieved within 90 min.展开更多
With the popularization of multi-variety and small-batch production patterns,the flexible job shop scheduling problem(FJSSP)has been widely studied.The sharing of processing resources by multiple machines frequently o...With the popularization of multi-variety and small-batch production patterns,the flexible job shop scheduling problem(FJSSP)has been widely studied.The sharing of processing resources by multiple machines frequently occurs due to space constraints in a flexible shop,which results in resource preemption for processing workpieces.Resource preemption complicates the constraints of scheduling problems that are otherwise difficult to solve.In this paper,the flexible job shop scheduling problem under the process resource preemption scenario is modeled,and a two-layer rule scheduling algorithm based on deep reinforcement learning is proposed to achieve the goal of minimum scheduling time.The simulation experiments compare our scheduling algorithm with two traditional metaheuristic optimization algorithms among different processing resource distribution scenarios in static scheduling environment.The results suggest that the two-layer rule scheduling algorithm based on deep reinforcement learning is more effective than the meta-heuristic algorithm in the application of processing resource preemption scenarios.Ablation experiments,generalization,and dynamic experiments are performed to demonstrate the excellent performance of our method for FJSSP under resource preemption.展开更多
基金This work was sponsored by grants from the National Natural Science Foundation of China(81803269 and 81427805)the Science and Technology Commission of Shanghai Municipality(18YF1412100 and 2019Y0150)+2 种基金the National Key Research and Development Program of China(2018YFC2000700)the Key Research Program of the Chinese Academy of Sciences(ZDRW-ZS-2017-1)Shanghai Municipality Health Commission(GWV-10.2-YQ17 and 2019Y0150).
文摘Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients.Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions.For the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic cancer.Moreover,CD44 was found to interact with integrin a6b4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling cascades.Notably,we also demonstrated that the CD44–a6b4 complex can be delivered to the target region via the paracrine effects of exosomes.The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor metastasis.Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.
基金supported in part by grants from the Programs of National Natural Science Foundation of China(No.81572372)National Key Research and Development Program“major chronic non-infectious disease research”(No.2016YFC1303202)National Key Research and Development Program“precision medicine research”(No.2017YFC0908304).
文摘Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior(No. 8 p,No. 12 b/p, No. 13, and No. 14 v), and para-aortic(No. 16 a2, and No. 16 b1) lymph nodes(LNs) in subtotal gastrectomy for advanced gastric antral carcinoma.Methods: A total of 203 patients with advanced gastric cancer(GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled.Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses. The therapeutic value index(TVI) was calculate to evaluate the survival benefit of dissecting each LN station.Results: Of 102 patients with D2-plus lymphadenectomy, 21(20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy. After matching, the overall survival(OS) was significantly better in the D2-plus than the D2 group(P=0.030). In the multivariate survival analysis, D2-plus lymphadenectomy(hazard ratio, 0.516;P=0.006) was confirmed to significantly improve the survival rate. In the logistic regression analysis, p N stage [odds ratio(OR), 2.533;95% confidence interval(95% CI), 1.368-4.691;P=0.003] and extent of LNs metastasis(OR, 5.965;95% CI, 1.335-26.650;P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy. The TVI of patient with metastasis to LNs station was 7.1(No. 8p), 5.7(No. 12p), 5.1(No. 13), and 7.1(both No. 16a2 and No. 16b1), respectively.Conclusions: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16.
基金This work was supported by grants from the National Natural Science Foundation of China(82173543,81803269,and 81902939)Shanghai Municipality Health Commission(GWV-10.2-YQ17 and 2019Y0150)+1 种基金Innovative Research Team of High-level Local Universities in Shanghai(YG2017QN68)the Major Science and Technology Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-01-E00059).
文摘Modern diets,which often feature high levels of fat and charcoal-grilled meat,contribute to the pathogenesis of obesity and non-alcoholic fatty liver disease(NAFLD),resulting in liver cancer progression.Benzo(a)pyrene(B[a]P)is a common environ-mental and foodborne pollutant found in smoke and fire-grilled foods,which can have an adverse effect on human health.Hepatocellular carcinoma(HCC)is the fifth leading cause of cancer and the second leading cause of cancer-related deaths worldwide.The epidemiological studies suggest that both environmental risk factors and chronic liver injury including NAFL are important for HCC development,but the precise mechanisms linking eating habits to hepato-carcinogenesis remain unclear.In the present study,we demonstrated that various miRNAs in B[a]P-exposed tumor cells contribute to tumor metastasis,among which miR-650 could be the most potent inducer.Furthermore,we found that the suppressor of cytokine signaling 3(SOCS3)is directly regulated by miR-650 and its suppression regulates the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3)cascade.Our findings reveal a possible adverse outcome pathway of SOCS3/JAK/STAT3 regulation in B[a]P-induced HCC progress.These results provide a better understanding of the adverse effects of chronic exposure to B[a]P on human health.
基金supported by the National High Technology Research and Development Program 863 of China (2011AA050509)National Natural Science Foundation of China (61106039)+1 种基金National Postdoctoral Foundation(2011049015)Jilin Province Youth Foundation(201101025)
文摘Fluorescence-based white-light-emitting diodes （WLEDs） were fabricated using blue GaN chips and green- and red-emitting CdSe/CdS/ZnS quantum dots （QDs）. The coordinate and color temperature of the WLEDs could be varied because of the size-tunable emission of CdSe QDs from 510 to 620 nm. Warm and cold white emissions were confirmed with the color temperature ranging from 4000 to 9000 K. Color coordinates were analyzed at different bias. The fast enhancement of blue emission resulted in the shift of color coordinates to the cold side. The stability of white emission during operation was analyzed; stable spectra were achieved within 90 min.
文摘With the popularization of multi-variety and small-batch production patterns,the flexible job shop scheduling problem(FJSSP)has been widely studied.The sharing of processing resources by multiple machines frequently occurs due to space constraints in a flexible shop,which results in resource preemption for processing workpieces.Resource preemption complicates the constraints of scheduling problems that are otherwise difficult to solve.In this paper,the flexible job shop scheduling problem under the process resource preemption scenario is modeled,and a two-layer rule scheduling algorithm based on deep reinforcement learning is proposed to achieve the goal of minimum scheduling time.The simulation experiments compare our scheduling algorithm with two traditional metaheuristic optimization algorithms among different processing resource distribution scenarios in static scheduling environment.The results suggest that the two-layer rule scheduling algorithm based on deep reinforcement learning is more effective than the meta-heuristic algorithm in the application of processing resource preemption scenarios.Ablation experiments,generalization,and dynamic experiments are performed to demonstrate the excellent performance of our method for FJSSP under resource preemption.
