The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural ...The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural enzyme-like stringent spatiotemporal structure-based catalytic activity regulation.Here,we report a subnanostructural transformable gold@ceria(STGC-PEG)nanozyme that performs tunable catalytic activities via near-infrared(NIR)light-mediated sub-nanostructural transformation.The gold core in STGC-PEG can generate energetic hot electrons upon NIR irradiation,wherein an internal sub-nanostructural transformation is initiated by the conversion between CeO;and electron-rich state of CeO;-x,and active oxygen vacancies generation via the hot-electron injection.Interestingly,the sub-nanostructural transformation of STGC-PEG enhances peroxidase-like activity and unprecedentedly activates plasmon-promoted oxidase-like activity,allowing highly efficient low-power NIR light(50 m W cm;)-activated photocatalytic therapy of tumors.Our atomic-level design and fabrication provide a platform to precisely regulate the catalytic activities of nanozymes via a light-mediated sub-nanostructural transformation,approaching natural enzyme-like activity control in complex living systems.展开更多
Ferroptosis, as a new type of cell death caused by lipid peroxidation, has attracted much attention since it was first identified in 2012. A lot of progress has been made in unraveling its mechanisms and therapeutic p...Ferroptosis, as a new type of cell death caused by lipid peroxidation, has attracted much attention since it was first identified in 2012. A lot of progress has been made in unraveling its mechanisms and therapeutic potential as a target for cancer therapy. Hitherto, there are mainly two strategies widely adopted for designing ferroptosis-inducing agents, which include increasing the intracellular reactive oxygen species(ROS) level by Fenton reaction, and inactivating the glutathione peroxidase 4(GPX4). In this mini-review,we summarize the recent advances in ferroptosis-based anticancer treatments with a highlight on nanomaterials, and discuss the current challenges faced by those agents from the perspective of in vivo applications. Moreover, by generalizing ferroptosis induced by excess iron ions to cell death caused by the polyvalent metal-mediated oxidative burden, we introduce a new paradigm of cancer treatment by exploiting various polyvalent metals to disrupt the vulnerable redox balance in cancer cells, which may greatly diversify our arsenal to combat cancer.展开更多
Age-related diseases(ARDs) are arising as a major threat to public health in our fast-aging society.Current development of nanomedicine has sparked much optimism toward ARDs management by improving drug delivery and c...Age-related diseases(ARDs) are arising as a major threat to public health in our fast-aging society.Current development of nanomedicine has sparked much optimism toward ARDs management by improving drug delivery and controlled drug release. However, effective treatments for ARDs, such as cancer and Alzheimer’s diseases(AD), are still lacking, due to the complicated pathological features of ARDs including multifactorial pathogenesis, intricate disease microenvironment, and dynamic symptom manifestation. Recently, dynamic supraparticles(DS), which are reversibly self-assembled functional nanoparticles, have provided a novel strategy for combating ARDs. Besides the intrinsic advantages of nanomedicine including multifunctional and multitarget, DS are capable of dynamic structural reconfiguration upon certain stimulation, creating another layer of maneuverability that allows programmed response to the spatiotemporal alterations of ARDs during progression and treatment. In this review,we will overview the challenges faced by ARDs management, and discuss the unique opportunities brought by DS. Then, we will summarize the designed synthesis of DS for ARDs treatment. Finally, we will dissect the therapeutic targets in ARDs that can be exploited by DS, and present the encouraging advances in this field. Hopefully, this review will bridge our knowledge of the design principle of DS and ARDs management, which may inspire the future development of potent theranostic agents to improve the healthcare.展开更多
In view of the problems of the existing mechanisms based on 2R open-chain planetary gear train for seedling transplanting,such as the bad tracking flexibility,low positioning accuracy,and high structure design difficu...In view of the problems of the existing mechanisms based on 2R open-chain planetary gear train for seedling transplanting,such as the bad tracking flexibility,low positioning accuracy,and high structure design difficulties of the mechanisms based on 3R open-chain planetary gear train for seedling manipulation.In this paper,a transplanting mechanism based on the solution domain synthesis of a 3R open-chain-based complete rotation kinematic pair,a gear train with a single cycle integral rotating pair,is designed.The Burmester curve equation is derived from the given transplanting trajectory and four exact poses corresponding to each other on the rotation center.Then,the open-chain road model of the 3R complete rotation kinematic pair is obtained under the constraint governed by the judgment condition of the hinge integral rotating pair.Meanwhile,combined with our developed in-house optimization software,the solution to the optimal parameters for the transplanting mechanism can be optimized according to the target trajectory.Finally,the feasibility of the design method is verified by transplanting testing,where kale seedlings with ages of about 20 d and heights of about 80-120 mm are used.The experimental results show that the actual motion trajectory of the prototype is basically identical to the theoretical trajectory,validating the feasibility of transplanting mechanism design,parts processing,and test-bed construction.Through the statistical analysis,the average success rate of transplanting is 90.625%,and the reliability of designed mechanism is satisfied.This study provides a promising solution for the seedling transplanting of two-planet scaffold pots.展开更多
At present,there is a lack of miniaturized and highly reliable plug seedling transplanting mechanism in flowerpots planting operation,in order to meet the needs of large displacement and high vertical uprightness for ...At present,there is a lack of miniaturized and highly reliable plug seedling transplanting mechanism in flowerpots planting operation,in order to meet the needs of large displacement and high vertical uprightness for flower transplanting,the paper combined the transmission characteristics of the non-circular gear planetary gear train with the swing flexibility of the cam gear and proposed a double planet carrier planetary gear transplanting mechanism.The linkage of the mechanism performs variable speed rotation relative to the first planet carrier,the linkage serves as the second planet carrier,and the transplanting arm performs variable speed swing relative to the linkage.A mathematical model of a single planetary carrier mechanism was first established using the method of open linkage group solution domain synthesis,then established the kinematic equations of the second planet carrier and the transplanting arm.The two parts are combined to form the mathematical solution model of the proposed mechanism.The initial trajectory was planned according to the trajectory requirements of seedlings planting operation,the non-circular gear pitch curve in the first planet carrier was obtained and the length of the first planet carrier is 120 mm.Then using the key points’angular deviation between the initial trajectory and the improved trajectory to obtain the cam parameters which driving the transplant arm,consequently determined the length of the second planet carrier is 69.25 mm and the length of the transplant arm is 112.4 mm.Finally,the prototype of the mechanism was manufactured,and the test verified the correctness of the design method of the double planet carrier planetary gear flower potting transplanting mechanism.The transplanting success rate of this mechanism reached 94.43%,and the plug seedlings planted in flowerpots had high uprightness.This research can provide a reference for the automatic development of research on flower transplanting machines.展开更多
Dear Editor,The intestinal epithelium is a rapidly self-renew-ing tissue for absorbing nutrients and providing bar-rier functions,and its homeostasis is orchestrated by several signaling pathways(Vermeulen and Snip-pe...Dear Editor,The intestinal epithelium is a rapidly self-renew-ing tissue for absorbing nutrients and providing bar-rier functions,and its homeostasis is orchestrated by several signaling pathways(Vermeulen and Snip-pert,2014;Zhu et al.,2021).Growing evidence dem-onstrates the importance of cell cycle regulation in intestinal homeostatic maintenance(McKernan and Egan,2015).Here,we report that the E3 ubiquitin ligase adaptor DDB1(Damaged DNA Binding Protein 1)is highly expressed in the intestinal epithelium and regulates the intestinal homeostasis by preventing cell cycle arrest.展开更多
基金We acknowledge financial support by the National Natural Science Foundation of China(32071374,32000985,81761148029,81620108028)Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan(21XD1422100)+3 种基金Leading Talent of“Ten Thousand Plan”-National High-Level Talents Special Support Plan,One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province(2019C04024)the Zhejiang Provincial Natural Science Foundation of China(LR22C100001,LGF19C100002,LQ21H300003)Zhejiang Province Medical and Health Science Research Project(2021KY666),and Zhejiang Pharmaceutical Association(2019ZYY12)Open access funding provided by Shanghai Jiao Tong University
文摘The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural enzyme-like stringent spatiotemporal structure-based catalytic activity regulation.Here,we report a subnanostructural transformable gold@ceria(STGC-PEG)nanozyme that performs tunable catalytic activities via near-infrared(NIR)light-mediated sub-nanostructural transformation.The gold core in STGC-PEG can generate energetic hot electrons upon NIR irradiation,wherein an internal sub-nanostructural transformation is initiated by the conversion between CeO;and electron-rich state of CeO;-x,and active oxygen vacancies generation via the hot-electron injection.Interestingly,the sub-nanostructural transformation of STGC-PEG enhances peroxidase-like activity and unprecedentedly activates plasmon-promoted oxidase-like activity,allowing highly efficient low-power NIR light(50 m W cm;)-activated photocatalytic therapy of tumors.Our atomic-level design and fabrication provide a platform to precisely regulate the catalytic activities of nanozymes via a light-mediated sub-nanostructural transformation,approaching natural enzyme-like activity control in complex living systems.
基金supported by the National Key Research and Development Program of China (No. 2016YFA0203600)the National Natural Science Foundation of China (Nos. 31822019, 91859116 and 51703195)+1 种基金the Fundamental Research Funds for the Central Universities (No. 2018QNA7020)the One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province (No. 2019C04024)
文摘Ferroptosis, as a new type of cell death caused by lipid peroxidation, has attracted much attention since it was first identified in 2012. A lot of progress has been made in unraveling its mechanisms and therapeutic potential as a target for cancer therapy. Hitherto, there are mainly two strategies widely adopted for designing ferroptosis-inducing agents, which include increasing the intracellular reactive oxygen species(ROS) level by Fenton reaction, and inactivating the glutathione peroxidase 4(GPX4). In this mini-review,we summarize the recent advances in ferroptosis-based anticancer treatments with a highlight on nanomaterials, and discuss the current challenges faced by those agents from the perspective of in vivo applications. Moreover, by generalizing ferroptosis induced by excess iron ions to cell death caused by the polyvalent metal-mediated oxidative burden, we introduce a new paradigm of cancer treatment by exploiting various polyvalent metals to disrupt the vulnerable redox balance in cancer cells, which may greatly diversify our arsenal to combat cancer.
基金supported by the National Key Research and Development Program of China (2016YFA0203600)the National Natural Science Foundation of China (31822019,51703195,and 91859116)+3 种基金One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province (2019C04024)the Zhejiang Provincial Natural Science Foundation (LGF19C100002)the Fundamental Research Funds for the Central Universities (2018QNA7020)‘‘Thousand Talents Program” for Distinguished Young Scholars
文摘Age-related diseases(ARDs) are arising as a major threat to public health in our fast-aging society.Current development of nanomedicine has sparked much optimism toward ARDs management by improving drug delivery and controlled drug release. However, effective treatments for ARDs, such as cancer and Alzheimer’s diseases(AD), are still lacking, due to the complicated pathological features of ARDs including multifactorial pathogenesis, intricate disease microenvironment, and dynamic symptom manifestation. Recently, dynamic supraparticles(DS), which are reversibly self-assembled functional nanoparticles, have provided a novel strategy for combating ARDs. Besides the intrinsic advantages of nanomedicine including multifunctional and multitarget, DS are capable of dynamic structural reconfiguration upon certain stimulation, creating another layer of maneuverability that allows programmed response to the spatiotemporal alterations of ARDs during progression and treatment. In this review,we will overview the challenges faced by ARDs management, and discuss the unique opportunities brought by DS. Then, we will summarize the designed synthesis of DS for ARDs treatment. Finally, we will dissect the therapeutic targets in ARDs that can be exploited by DS, and present the encouraging advances in this field. Hopefully, this review will bridge our knowledge of the design principle of DS and ARDs management, which may inspire the future development of potent theranostic agents to improve the healthcare.
基金The authors acknowledge that this work was financially supported by the National Natural Science Foundation of China(Grant No.32071909,51975536)the Key Research Projects of Zhejiang Province(Grant No.2022C02002,2021C02021)+2 种基金the Basic Public Welfare Research Projects of Zhejiang Province(Grant No.LGN20E050006)the Shanghai Science and technology agricultural Development Project(2021 No 4-1)the General Project of Agriculture and Social Development in Hangzhou(Grant No.20201203B92).
文摘In view of the problems of the existing mechanisms based on 2R open-chain planetary gear train for seedling transplanting,such as the bad tracking flexibility,low positioning accuracy,and high structure design difficulties of the mechanisms based on 3R open-chain planetary gear train for seedling manipulation.In this paper,a transplanting mechanism based on the solution domain synthesis of a 3R open-chain-based complete rotation kinematic pair,a gear train with a single cycle integral rotating pair,is designed.The Burmester curve equation is derived from the given transplanting trajectory and four exact poses corresponding to each other on the rotation center.Then,the open-chain road model of the 3R complete rotation kinematic pair is obtained under the constraint governed by the judgment condition of the hinge integral rotating pair.Meanwhile,combined with our developed in-house optimization software,the solution to the optimal parameters for the transplanting mechanism can be optimized according to the target trajectory.Finally,the feasibility of the design method is verified by transplanting testing,where kale seedlings with ages of about 20 d and heights of about 80-120 mm are used.The experimental results show that the actual motion trajectory of the prototype is basically identical to the theoretical trajectory,validating the feasibility of transplanting mechanism design,parts processing,and test-bed construction.Through the statistical analysis,the average success rate of transplanting is 90.625%,and the reliability of designed mechanism is satisfied.This study provides a promising solution for the seedling transplanting of two-planet scaffold pots.
基金This work was financially supported by the National Key Research and Development Program of China(Grant No.2017YFD0700800)the National Natural Science Foundation of China(Grant No.32071909,No.51775512)+1 种基金Basic public welfare research projects of Zhejiang Province(Grant No.LGN19E050002,No.LGN20E050006)Fundamental Research Funds of Zhejiang Sci-Tech University(Grant No.2020Q013).
文摘At present,there is a lack of miniaturized and highly reliable plug seedling transplanting mechanism in flowerpots planting operation,in order to meet the needs of large displacement and high vertical uprightness for flower transplanting,the paper combined the transmission characteristics of the non-circular gear planetary gear train with the swing flexibility of the cam gear and proposed a double planet carrier planetary gear transplanting mechanism.The linkage of the mechanism performs variable speed rotation relative to the first planet carrier,the linkage serves as the second planet carrier,and the transplanting arm performs variable speed swing relative to the linkage.A mathematical model of a single planetary carrier mechanism was first established using the method of open linkage group solution domain synthesis,then established the kinematic equations of the second planet carrier and the transplanting arm.The two parts are combined to form the mathematical solution model of the proposed mechanism.The initial trajectory was planned according to the trajectory requirements of seedlings planting operation,the non-circular gear pitch curve in the first planet carrier was obtained and the length of the first planet carrier is 120 mm.Then using the key points’angular deviation between the initial trajectory and the improved trajectory to obtain the cam parameters which driving the transplant arm,consequently determined the length of the second planet carrier is 69.25 mm and the length of the transplant arm is 112.4 mm.Finally,the prototype of the mechanism was manufactured,and the test verified the correctness of the design method of the double planet carrier planetary gear flower potting transplanting mechanism.The transplanting success rate of this mechanism reached 94.43%,and the plug seedlings planted in flowerpots had high uprightness.This research can provide a reference for the automatic development of research on flower transplanting machines.
基金This work was supported by grants from the National Natural Science Foundation of China(31988101 and 31730056 to YGC)the National Key Research and Development Program of China(2017YFA0103601 to YGC).
文摘Dear Editor,The intestinal epithelium is a rapidly self-renew-ing tissue for absorbing nutrients and providing bar-rier functions,and its homeostasis is orchestrated by several signaling pathways(Vermeulen and Snip-pert,2014;Zhu et al.,2021).Growing evidence dem-onstrates the importance of cell cycle regulation in intestinal homeostatic maintenance(McKernan and Egan,2015).Here,we report that the E3 ubiquitin ligase adaptor DDB1(Damaged DNA Binding Protein 1)is highly expressed in the intestinal epithelium and regulates the intestinal homeostasis by preventing cell cycle arrest.