The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ab...The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.展开更多
Virtual prototype of pipe wagon articulating (PWA) system has been developed and simulated based on the kinematics and dynamics of machinery and Automatic Dynamic Analysis of Mechanical Systems (ADAMS) software. It ha...Virtual prototype of pipe wagon articulating (PWA) system has been developed and simulated based on the kinematics and dynamics of machinery and Automatic Dynamic Analysis of Mechanical Systems (ADAMS) software. It has been integrated with real-time three dimensional (3-D) system simulations for detailed and responsive interaction with dynamic virtual environments. By using this virtual model, the conceptual design examination and performance analysis of the PWA system have been realized dynamically in virtual laboratory. System dynamic force, displacement and tension of pipe have been measured through verifying this 3- D virtual prototype. By comparing the static tension and dynamic tension of pipe, the difference between the two kind tensions has been found. The simulated dynamic tension is much greater than the static tension obtained from the static theory. The results attained in this work suggest that the conceptual designed PWA system can meet the requirements of the operation.展开更多
The indoor subarea localization has wide application space in dynamic hotzone identification, indoor layout optimization, store dynamic pricing and crowd flowtrend prediction. The ubiquitous mobile devices provide the...The indoor subarea localization has wide application space in dynamic hotzone identification, indoor layout optimization, store dynamic pricing and crowd flowtrend prediction. The ubiquitous mobile devices provide the opportunity for wirelessfingerprinting-based indoor localization services. However, there are two short boardwhere the existing methods have been criticized. One is that a tagging approach requiresa large number of professional surveys for wireless fingerprint construction, whichweakens the scalability of the methods. The other is that the crowdsourcing-basedmethods encounter the cold boot problem in the system initial stage. To address theseissues, the paper proposes a topology optimization approach leveraging the dynamiclogical anchor selection into a subarea localization system. First of all, a newannular-based radio map construction strategy with the feedback selection of logic anchoris designed to release the pressure of site survey. The implementation of this strategyharnesses the characteristics of the indoor building structure and inter subareaoverlapping recognition, without the topology and distribution of physical anchor (e.g.,access points or POIs). Secondly, exploiting the probabilistic support vector machinealgorithm, the target is localized in the corresponding subarea in a real-time pattern.Furthermore, the localization error is calibrated with an error recognition algorithm.Finally, massive experiments are implemented on a prototype system. The results showthat the proposed method can decrease the overhead of the system initialization andachieve higher localization accuracy compared with the existing approaches.展开更多
Abnormal protein expression or activities are associated with many diseases,especially cancer.Therefore,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treat...Abnormal protein expression or activities are associated with many diseases,especially cancer.Therefore,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treatment—a number of drugs based on proteolysis-targeting chimaera(PROTAC)mechanism have demonstrated clinical efficacy.Recent progress in the PROTAC strategy includes identification of the structure of the first ternary eutectic complex,extra-terminal domain-4-PROTAC-VonHippel-Lindau(BRD4-PROTAC-VHL),and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019.These discoveries strongly proved the value of the PROTAC strategy.In this review,we summarize recent meaningful research of PROTACs,including the molecular design and optimization strategy as well as clinical application of candidate molecules.We hope to provide useful insights for rational design of PROTACs.展开更多
Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including sm...Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including small molecule inhibitors,viral therapies,cancer vaccines,and monoclonal antibodies.Among them,the unique advantages of small molecule inhibitors have made them a focus of attention in the drug discovery of glioblastoma.Currently,the most used chemotherapeutic agents are small molecule inhibitors that target key dysregulated signaling pathways in glioblastoma,including receptor tyrosine kinase,PI3K/AKT/mTOR pathway,DNA damage response,TP53 and cell cycle inhibitors.This review analyzes the therapeutic benefit and clinical development of novel small molecule inhibitors discovered as promising anti-glioblastoma agents by the related targets of these major pathways.Meanwhile,the recent advances in temozolomide resistance and drug combination are also reviewed.In the last part,due to the constant clinical failure of targeted therapies,this paper reviewed the research progress of other therapeutic methods for glioblastoma,to provide patients and readers with a more comprehensive understanding of the treatment landscape of glioblastoma.展开更多
The problem of data right confirmation is a long-term bottleneck in data sharing.Existing methods for confirming data rights lack credibility owing to poor supervision,and work only with specific data types because of...The problem of data right confirmation is a long-term bottleneck in data sharing.Existing methods for confirming data rights lack credibility owing to poor supervision,and work only with specific data types because of their technical limitations.The emergence of blockchain is followed by some new data-sharing models that may provide improved data security.However,few of these models perform well enough in confirming data rights because the data access could not be fully under the control of the blockchain facility.In view of this,we propose a right-confirmable data-sharing model named RCDS that features symbol mapping coding(SMC)and blockchain.With SMC,each party encodes its digital identity into the byte sequence of the shared data by generating a unique symbol mapping table,whereby declaration of data rights can be content-independent for any type and any volume of data.With blockchain,all data-sharing participants jointly supervise the delivery and the access to shared data,so that granting of data rights can be openly verified.The evaluation results show that RCDS is effective and practical in data-sharing applications that are conscientious about data right confirmation.展开更多
By its unparalleled capacity to manipulate optical parameters,metasurfaces demonstrate the ability to simultaneously manipulate the amplitude and phase of incident light.Exhibiting both near-field nanoprinting images ...By its unparalleled capacity to manipulate optical parameters,metasurfaces demonstrate the ability to simultaneously manipulate the amplitude and phase of incident light.Exhibiting both near-field nanoprinting images and far-field holography images is a quintessential illustration of this capability.In preceding investigations,image multiplexing commonly transpires within the single polarization state or orthogonal polarization states,thereby exhibiting a deficiency in terms of information security when contrasted with the nonorthogonal polarization states.In this research,a multifunctional metasurface with the capability of exhibiting four-channel images has been proposed by using a nanobrick as a quarter-wave plate.Through the adjustment of the orientation angles of each nanobrick,nanoprinting can be displayed under both linearly and circularly polarized light.Building on this,the propagation phase is combined with the geometric phase to generate diverse phase delays,enabling the metasurface to be multiplexed under two nonorthogonal polarization states to achieve four-channel image displays.Intriguingly,bidirectional nanoprinting and bidirectional holography can be achieved by altering the direction of incidence polarization states.The proposed metasurface platform can open new possibilities for creating compact multifunctional optical devices,while also enhancing applications in multichannel image displays,information anticounterfeiting,and encryption.展开更多
We designed and demonstrated experimentally a silicon photonics integrated dynamic polarization controller.The overall size of the dynamic polarization controller on chip is 2.830 mm × 0.210 mm × 1 mm.The mo...We designed and demonstrated experimentally a silicon photonics integrated dynamic polarization controller.The overall size of the dynamic polarization controller on chip is 2.830 mm × 0.210 mm × 1 mm.The modulation bandwidth is 30 kHz.By using a variable step simulated annealing approach,we achieve a dynamic polarization extinction ratio greater than 25 dB.A numerical simulation method was used to optimize the relevant parameters of the dynamic polarization controller.It is expected that the dynamic polarization controller can be utilized in fiber communication systems or silicon photonics integrated quantum communication systems to minimize the size and decrease the cost further.展开更多
基金financially supported by the National Natural Science Foundation of China (Grant Nos. 81703382 and 81673567)
文摘The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.
文摘Virtual prototype of pipe wagon articulating (PWA) system has been developed and simulated based on the kinematics and dynamics of machinery and Automatic Dynamic Analysis of Mechanical Systems (ADAMS) software. It has been integrated with real-time three dimensional (3-D) system simulations for detailed and responsive interaction with dynamic virtual environments. By using this virtual model, the conceptual design examination and performance analysis of the PWA system have been realized dynamically in virtual laboratory. System dynamic force, displacement and tension of pipe have been measured through verifying this 3- D virtual prototype. By comparing the static tension and dynamic tension of pipe, the difference between the two kind tensions has been found. The simulated dynamic tension is much greater than the static tension obtained from the static theory. The results attained in this work suggest that the conceptual designed PWA system can meet the requirements of the operation.
文摘The indoor subarea localization has wide application space in dynamic hotzone identification, indoor layout optimization, store dynamic pricing and crowd flowtrend prediction. The ubiquitous mobile devices provide the opportunity for wirelessfingerprinting-based indoor localization services. However, there are two short boardwhere the existing methods have been criticized. One is that a tagging approach requiresa large number of professional surveys for wireless fingerprint construction, whichweakens the scalability of the methods. The other is that the crowdsourcing-basedmethods encounter the cold boot problem in the system initial stage. To address theseissues, the paper proposes a topology optimization approach leveraging the dynamiclogical anchor selection into a subarea localization system. First of all, a newannular-based radio map construction strategy with the feedback selection of logic anchoris designed to release the pressure of site survey. The implementation of this strategyharnesses the characteristics of the indoor building structure and inter subareaoverlapping recognition, without the topology and distribution of physical anchor (e.g.,access points or POIs). Secondly, exploiting the probabilistic support vector machinealgorithm, the target is localized in the corresponding subarea in a real-time pattern.Furthermore, the localization error is calibrated with an error recognition algorithm.Finally, massive experiments are implemented on a prototype system. The results showthat the proposed method can decrease the overhead of the system initialization andachieve higher localization accuracy compared with the existing approaches.
基金supported by the National Program on Key Research Project of China(2019YFE0103900)as well as the European Union's Horizon 2020 Research and Innovation Program(861917-SAFFI)Zhejiang Provincial Key R&D Program of China(2023C03045)+3 种基金Ningbo Public Service Technology Foundation,China(2021S155)the Medical Scientific Research Foundationof Zhejang Province,China(2022KY1158 and 2024KY1557)Ningbo Natural Science Foundation,China(2023J203)Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(2021JJLH0083).
基金the support from grants(Nos.81573281)of National Natural Science Foundation of Chinasupport from Double First-Class initiative Innovation team project of China Pharmaceutical University(Nos.CPU2018GF11 and CPU2018GY34,China).
文摘Abnormal protein expression or activities are associated with many diseases,especially cancer.Therefore,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treatment—a number of drugs based on proteolysis-targeting chimaera(PROTAC)mechanism have demonstrated clinical efficacy.Recent progress in the PROTAC strategy includes identification of the structure of the first ternary eutectic complex,extra-terminal domain-4-PROTAC-VonHippel-Lindau(BRD4-PROTAC-VHL),and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019.These discoveries strongly proved the value of the PROTAC strategy.In this review,we summarize recent meaningful research of PROTACs,including the molecular design and optimization strategy as well as clinical application of candidate molecules.We hope to provide useful insights for rational design of PROTACs.
基金We gratefully thank the support from the grants(Nos.82173652,81872728,81830105 and 81973207)of National Natural Science Foundation of China(Nos.BK20191411)of Natural Science Foundation of Jiangsu Province.
文摘Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including small molecule inhibitors,viral therapies,cancer vaccines,and monoclonal antibodies.Among them,the unique advantages of small molecule inhibitors have made them a focus of attention in the drug discovery of glioblastoma.Currently,the most used chemotherapeutic agents are small molecule inhibitors that target key dysregulated signaling pathways in glioblastoma,including receptor tyrosine kinase,PI3K/AKT/mTOR pathway,DNA damage response,TP53 and cell cycle inhibitors.This review analyzes the therapeutic benefit and clinical development of novel small molecule inhibitors discovered as promising anti-glioblastoma agents by the related targets of these major pathways.Meanwhile,the recent advances in temozolomide resistance and drug combination are also reviewed.In the last part,due to the constant clinical failure of targeted therapies,this paper reviewed the research progress of other therapeutic methods for glioblastoma,to provide patients and readers with a more comprehensive understanding of the treatment landscape of glioblastoma.
基金supported by the National Natural Science Foundation of China (22176060)Shanghai Municipal Science and Technology Major Project (2018SHZDZX03)+3 种基金the Program of Introducing Talents of Discipline to Universities (B16017)Science and Technology Commission of Shanghai Municipality (20DZ2250400)Shanghai Sailing Program (20YF1410600)the Fundamental Research Funds for the Central Universities (222201717003)。
基金Project supported by the Natural Science Foundation of Hebei Province,China(No.F2023201032)the S&T Program of Hebei Province,China(No.20310105D)。
文摘The problem of data right confirmation is a long-term bottleneck in data sharing.Existing methods for confirming data rights lack credibility owing to poor supervision,and work only with specific data types because of their technical limitations.The emergence of blockchain is followed by some new data-sharing models that may provide improved data security.However,few of these models perform well enough in confirming data rights because the data access could not be fully under the control of the blockchain facility.In view of this,we propose a right-confirmable data-sharing model named RCDS that features symbol mapping coding(SMC)and blockchain.With SMC,each party encodes its digital identity into the byte sequence of the shared data by generating a unique symbol mapping table,whereby declaration of data rights can be content-independent for any type and any volume of data.With blockchain,all data-sharing participants jointly supervise the delivery and the access to shared data,so that granting of data rights can be openly verified.The evaluation results show that RCDS is effective and practical in data-sharing applications that are conscientious about data right confirmation.
基金supported by the National Natural Science Foundation of China (NSFC) (Nos.62175070 and 61774062)the Natural Science Foundation of Guangdong Province (No.2021A1515010352)the Science and Technology Program of Guangzhou (No.2019050001)。
文摘By its unparalleled capacity to manipulate optical parameters,metasurfaces demonstrate the ability to simultaneously manipulate the amplitude and phase of incident light.Exhibiting both near-field nanoprinting images and far-field holography images is a quintessential illustration of this capability.In preceding investigations,image multiplexing commonly transpires within the single polarization state or orthogonal polarization states,thereby exhibiting a deficiency in terms of information security when contrasted with the nonorthogonal polarization states.In this research,a multifunctional metasurface with the capability of exhibiting four-channel images has been proposed by using a nanobrick as a quarter-wave plate.Through the adjustment of the orientation angles of each nanobrick,nanoprinting can be displayed under both linearly and circularly polarized light.Building on this,the propagation phase is combined with the geometric phase to generate diverse phase delays,enabling the metasurface to be multiplexed under two nonorthogonal polarization states to achieve four-channel image displays.Intriguingly,bidirectional nanoprinting and bidirectional holography can be achieved by altering the direction of incidence polarization states.The proposed metasurface platform can open new possibilities for creating compact multifunctional optical devices,while also enhancing applications in multichannel image displays,information anticounterfeiting,and encryption.
基金This work was supported by the Aeronautical Science Foundation of China(No.20200020115001)National Natural Science Foundation of China(No.62175138)+1 种基金Key Research and Development Program of Guangdong Province(No.2020B0303040002),Shanxi 1331KSCOpen Project of the State Key Laboratory of Quantum Optics and Quantum Optics Devices of Shanxi University(No.KF202006).
文摘We designed and demonstrated experimentally a silicon photonics integrated dynamic polarization controller.The overall size of the dynamic polarization controller on chip is 2.830 mm × 0.210 mm × 1 mm.The modulation bandwidth is 30 kHz.By using a variable step simulated annealing approach,we achieve a dynamic polarization extinction ratio greater than 25 dB.A numerical simulation method was used to optimize the relevant parameters of the dynamic polarization controller.It is expected that the dynamic polarization controller can be utilized in fiber communication systems or silicon photonics integrated quantum communication systems to minimize the size and decrease the cost further.
