Cavitation has a significant e ect on the flow fields and structural behaviors of a centrifugal pump. In this study, the unsteady flow and structural behaviors of a centrifugal pump are investigated numerically under ...Cavitation has a significant e ect on the flow fields and structural behaviors of a centrifugal pump. In this study, the unsteady flow and structural behaviors of a centrifugal pump are investigated numerically under di erent cavitation conditions. A strong two-way coupling fluid-structure interaction simulation is applied to obtain interior views of the e ects of cavitating bubbles on the flow and structural dynamics of a pump. The renormalization-group k-ε turbulence model and the Zwart–Gerbe–Belamri cavitation model are solved for the fluid side, while a transient structural dynamic analysis is employed for the structure side. The di erent cavitation states are mapped in the head-net positive suction head(H-NPSH) curves and flow field features inside the impeller are fully revealed. Results indicate that cavitating bubbles grow and expand rapidly with decreasing NPSH. In addition, the pressure fluctuations, both in the impeller and volute, are quantitatively analyzed and associated with the cavitation states. It is shown that influence of the cavitation on the flow field is critical, specifically in the super-cavitation state. The e ect of cavitation on the unsteady radial force and blade loads is also discussed. The results indicate that the averaged radial force increased from 8.5 N to 54.4 N in the transition progress from an onset cavitation state to a super-cavitation state. Furthermore, the structural behaviors, including blade deformation, stress, and natural frequencies, corresponding to the cavitation states are discussed. A large volume of cavitating bubbles weakens the fluid forces on the blade and decreases the natural frequencies of the rotor system. This study could enhance the understanding of the e ects of cavitation on pump flow and structural behaviors.展开更多
Esophageal squamous cell carcinoma （ESCC） is one of the most aggressive cancers in China, but the underlying molecular mechanism of ESCC is still unclear. Involvement of micro- RNAs has been demonstrated in cancer i...Esophageal squamous cell carcinoma （ESCC） is one of the most aggressive cancers in China, but the underlying molecular mechanism of ESCC is still unclear. Involvement of micro- RNAs has been demonstrated in cancer initiation and progression. Despite the reported function of miR-503 in several human cancers, its detailed anti-oncogenic role and clinical significance in ESCC remain undefined. In this study, we examined miR-503 expression by qPCR and found the downregulation of miR-503 expression in ESCC tissue relative to adjacent normal tissues. Fur- ther investigation in the effect of miR-503 on ESCC cell proliferation, migration, and invasion showed that enhanced expression of miR-503 inhibited ESCC aggressive phenotype and overexpres- sion of CCND1 reversed the effect of miR-503-mediated ESCC cell aggressive phenotype. Our study further identified CCND1 as the target gene of miR-503. Thus, miR-503 functions as a tumor suppressor and has an important role in ESCC by targeting CCND1.展开更多
Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of eff...Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of mi R-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined.Here, we found that mi R-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified mi R-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of mi R-503-3p in breast cancer cells inhibited expression of epithelialemesenchymal transition（EMT）-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their m RNA30 untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for mi R-503-3p in induction of breast cancer EMT and suggest that plasma mi R-503-3p may be a useful diagnostic biomarker for breast cancer.展开更多
Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins,aged or malfunctioning organelles,which is essential for the intracellular homeostasis and prevention of malignant transformati...Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins,aged or malfunctioning organelles,which is essential for the intracellular homeostasis and prevention of malignant transformation.Although the processes of autophagosome biogenesis have been well illuminated,the mechanism of autophagosome transport remains largely unclear.In this study,we demonstrated that the ninein-like protein(Nip),a well-characterized centrosomal associated protein,was able to modulate autophagosome transport and facilitate autophagy.During autophagy,Nip colocalized with autophagosomes and physically interacted with autophagosome marker LC3,autophagosome sorting protein Rab7 and its downstream effector FYCOl.Interestingly,Nip enhanced the interaction between Rab7 and FYC01,thus accelerated autophagic flux and the formation of autophagolysosomes.Furthermore,compared to the wild-type mice,NLP deficient mice treated with chemical agent DMBA were prone to increased incidence of hepatomegaly and liver cancer,which were tight associated with the hepatic autophagic defect.Taken together,our findings provide a new insight for the first time that the well-known centrosomal protein Nip is also a new regulator of autophagy,which promotes the interaction of Rab7 and FYC01 and facilitates the formation of autophagolysosome.展开更多
基金Supported by National Natural Science Foundation of China(Grant Nos.51609212,51606167)China Postdoctoral Science Foundation(Grant No.2016M590546)Zhejiang Provincial Natural Science Foundation(Grant No.2016C31043)
文摘Cavitation has a significant e ect on the flow fields and structural behaviors of a centrifugal pump. In this study, the unsteady flow and structural behaviors of a centrifugal pump are investigated numerically under di erent cavitation conditions. A strong two-way coupling fluid-structure interaction simulation is applied to obtain interior views of the e ects of cavitating bubbles on the flow and structural dynamics of a pump. The renormalization-group k-ε turbulence model and the Zwart–Gerbe–Belamri cavitation model are solved for the fluid side, while a transient structural dynamic analysis is employed for the structure side. The di erent cavitation states are mapped in the head-net positive suction head(H-NPSH) curves and flow field features inside the impeller are fully revealed. Results indicate that cavitating bubbles grow and expand rapidly with decreasing NPSH. In addition, the pressure fluctuations, both in the impeller and volute, are quantitatively analyzed and associated with the cavitation states. It is shown that influence of the cavitation on the flow field is critical, specifically in the super-cavitation state. The e ect of cavitation on the unsteady radial force and blade loads is also discussed. The results indicate that the averaged radial force increased from 8.5 N to 54.4 N in the transition progress from an onset cavitation state to a super-cavitation state. Furthermore, the structural behaviors, including blade deformation, stress, and natural frequencies, corresponding to the cavitation states are discussed. A large volume of cavitating bubbles weakens the fluid forces on the blade and decreases the natural frequencies of the rotor system. This study could enhance the understanding of the e ects of cavitation on pump flow and structural behaviors.
基金supported by the funding from the National Natural Science Foundation of China(Grant Nos.81472661 and 81402463)CAMS Innovation Fund for Medical Sciences(CIFMSGrant No.2016-I2M-1-001)
文摘Esophageal squamous cell carcinoma （ESCC） is one of the most aggressive cancers in China, but the underlying molecular mechanism of ESCC is still unclear. Involvement of micro- RNAs has been demonstrated in cancer initiation and progression. Despite the reported function of miR-503 in several human cancers, its detailed anti-oncogenic role and clinical significance in ESCC remain undefined. In this study, we examined miR-503 expression by qPCR and found the downregulation of miR-503 expression in ESCC tissue relative to adjacent normal tissues. Fur- ther investigation in the effect of miR-503 on ESCC cell proliferation, migration, and invasion showed that enhanced expression of miR-503 inhibited ESCC aggressive phenotype and overexpres- sion of CCND1 reversed the effect of miR-503-mediated ESCC cell aggressive phenotype. Our study further identified CCND1 as the target gene of miR-503. Thus, miR-503 functions as a tumor suppressor and has an important role in ESCC by targeting CCND1.
基金supported by funding from the National Key Basic Research Program of China(973 Program,No.2012CB967003)the National Natural Science Foundation of China(Nos.81472661,21335007,and 81402463)the National High Technology Research and Development Program of China(863 Program,No.2015AA020104)
文摘Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of mi R-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined.Here, we found that mi R-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified mi R-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of mi R-503-3p in breast cancer cells inhibited expression of epithelialemesenchymal transition（EMT）-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their m RNA30 untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for mi R-503-3p in induction of breast cancer EMT and suggest that plasma mi R-503-3p may be a useful diagnostic biomarker for breast cancer.
基金This work was supported by the National Natural Science Foundation of China(81988101,81802780,and 81830086)Beijing Municipal Commission of Health and Family Planning Project(PXM2018_026279_000005)+5 种基金Beijing Nova Program(Z191100001119038)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-081)Science Foundation of Peking University Cancer Hospital(2020-8)Funding by Major Program of Shenzhen Bay Laboratory(S201101004)Guangdong Basic and Applied Basic Research Foundation(2019B030302012)the Fund of"San-ming"Project of Medicine in Shenzhen(No.SZSM201812088).
文摘Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins,aged or malfunctioning organelles,which is essential for the intracellular homeostasis and prevention of malignant transformation.Although the processes of autophagosome biogenesis have been well illuminated,the mechanism of autophagosome transport remains largely unclear.In this study,we demonstrated that the ninein-like protein(Nip),a well-characterized centrosomal associated protein,was able to modulate autophagosome transport and facilitate autophagy.During autophagy,Nip colocalized with autophagosomes and physically interacted with autophagosome marker LC3,autophagosome sorting protein Rab7 and its downstream effector FYCOl.Interestingly,Nip enhanced the interaction between Rab7 and FYC01,thus accelerated autophagic flux and the formation of autophagolysosomes.Furthermore,compared to the wild-type mice,NLP deficient mice treated with chemical agent DMBA were prone to increased incidence of hepatomegaly and liver cancer,which were tight associated with the hepatic autophagic defect.Taken together,our findings provide a new insight for the first time that the well-known centrosomal protein Nip is also a new regulator of autophagy,which promotes the interaction of Rab7 and FYC01 and facilitates the formation of autophagolysosome.
