The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies oft...The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death(ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators.Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.展开更多
Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lackin...Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side effects.According to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and receptors.Recently,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer therapy.Herein,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug delivery.We summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.展开更多
The simultaneous placement of different types of materials including polymers,ceramics,and metals,in their desired positions could be adopted to manufacture end-use devices/apparatuses with diverse functionalities and...The simultaneous placement of different types of materials including polymers,ceramics,and metals,in their desired positions could be adopted to manufacture end-use devices/apparatuses with diverse functionalities and significantly reduce the fabrication cost and time.However,existing additive manufacturing(AM)approaches can only treat one material species at a time due to their intrinsic working mechanisms.Here we develop an AM manipulator for manufacturing a wide variety of material species,including polymers,ceramics,and metals,through a multifilament transport strategy assisted by laser power.The six-jaw manipulator contains three pairs of filament delivering/cutting systems for transporting diverse materials and a beam of tunable laser as the thermal source.The whole apparatus is integrated into a robotic manipulator to create a multifreedom manufacturing platform.With this innovation,products with multiple material species and desired complex geometries can be fabricated on demand.Furthermore,we synthesize a multimaterial(polymer/ceramic/metal)printed magnetoelectric pressure sensor that can convert applied mechanical forces to electricity and maintain efficiency even after undergoing 10000 cycles of pressure/recovery.With this multimaterial filament transport and laser manufacturing strategy,our AM manipulator exhibits promising application in the advanced manufacturing of embedded electronics,sensors,soft robotics,and customizable medical devices.展开更多
Hydrogen sulfide(H_(2)S)is the most recently discovered gasotransmitter molecule that activates multiple intracellular signaling pathways and exerts concentration-dependent antitumor effect by interfering with mitocho...Hydrogen sulfide(H_(2)S)is the most recently discovered gasotransmitter molecule that activates multiple intracellular signaling pathways and exerts concentration-dependent antitumor effect by interfering with mitochondrial respiration and inhibiting cellular ATP generation.Inspired by the fact that H_(2)S can also serve as a promoter for intracellular Ca^(2+)influx,tumor-specific nanomodulators(I-CaS@PP)have been constructed by encapsulating calcium sulfide(CaS)and indocyanine green(ICG)into methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PLGA-PEG).I-CaS@PP can achieve tumor-specific biodegradability with high biocompatibility and pH-responsive H_(2)S release.The released H_(2)S can effectively suppress the catalase(CAT)activity and synergize with released Ca^(2+)to facilitate abnormal Ca^(2+)retention in cells,thus leading to mitochondria destruction and amplification of oxidative stress.Mitochondrial dysfunction further contributes to blocking ATP synthesis and downregulating heat shock proteins(HSPs)expression,which is beneficial to overcome the heat endurance of tumor cells and strengthen ICG-induced photothermal performance.Such a H_(2)S-boosted Ca^(2+)-involved tumor-specific therapy exhibits highly effective tumor inhibition effect with almost complete elimination within 14-day treatment,indicating the great prospect of CaS-based nanomodulators as antitumor therapeutics.展开更多
Porous structure design on the contact surface is crucial to promote the osseointegration of the intervertebral cage while preventing subsidence and displacement.However,the stress response will undergo significant ch...Porous structure design on the contact surface is crucial to promote the osseointegration of the intervertebral cage while preventing subsidence and displacement.However,the stress response will undergo significant changes for the current random porous cages,which can directly affect the mechanical properties and long-term usability.Here,this paper proposed a newly designed polyetheretherketone(PEEK)cage with the triply periodic minimal surface(TPMS)-structured lattice surfaces to provide tailored 3 D microporosity and studied the mechanical performance,stress/strain responses,and microstructure changes in depth.The lattice-surfaced PEEK cage mainly exhibits a multiple-point-plane stress transfer mechanism.The compression modulus and elastic limit can be adjusted by controlling the area of the Diamond TPMS surface while the energy absorption efficiency remains stable.The microstructure of high-strength PEEK is featured by the radial pattern morphology.Meanwhile,the double-stranded orthorhombic phase is more ordered,and the benzene plane subunit and lattice volume become more expanded.展开更多
目的:探讨胃癌病人淋巴结转移率分组界值及其对预后的评估。方法:回顾性分析2004年1月至2008年7月复旦大学附属中山医院392例行胃癌根治术,分期为美国癌症联合委员会(American Joint Committee on Cancer,AJCC)(第8版)Ⅱ~Ⅲ期的病人。利...目的:探讨胃癌病人淋巴结转移率分组界值及其对预后的评估。方法:回顾性分析2004年1月至2008年7月复旦大学附属中山医院392例行胃癌根治术,分期为美国癌症联合委员会(American Joint Committee on Cancer,AJCC)(第8版)Ⅱ~Ⅲ期的病人。利用X-tile软件进行淋巴结转移率的分组,评估淋巴结转移率与其他临床病理因素的相关性和对病人预后的评估。建立列线图预测模型,绘制校准曲线,与实际作比较。用Bootstrap法进行内部验证,计算一致性指数(C-index)评估模型准确性。结果:X-tile获得淋巴结转移率的最佳截断值为0.20(20%)和0.70(70%)。将淋巴结转移率分为1组(0~20%)、2组(21%~69%)和3组(70%~100%)。3组病人的生存差异有统计学意义(P<0.001)。单因素分析显示,淋巴结转移率、TNM分期、T分期、N分期、淋巴管浸润和年龄是影响预后的相关因素。多因素分析显示,淋巴结转移率、T分期、N分期、淋巴管浸润及年龄是影响预后的独立因素。分别以淋巴结转移率、TNM分期、淋巴管浸润及年龄绘制病人总体生存率的受试者操作特征曲线,其曲线下面积分别为0.699、0.667、0.587、0.561。采用淋巴结转移率、TNM分期、淋巴管浸润和年龄构建列线图预测模型,其C-index为0.707(95%CI:0.705~0.708)。校正曲线显示的1、3及5年预测生存率与实际相符。结论:淋巴结转移率是影响Ⅱ~Ⅲ期胃癌根治术后病人生存的独立危险因素。在判断Ⅱ~Ⅲ期胃癌根治术后病人预后时,淋巴结转移率是N分期的有效补充,可指导合理治疗。展开更多
基金supported by the National Natural Science Foundation of China(22007106,31800842,31922042 and 81771966)Technology&Innovation Commission of Shenzhen Municipality(JCYJ20180507181654186 and JCYJ20170818162637217,China)+1 种基金the Fundamental Research Funds for the Central Universities(2020-RC320-002 and 2019PT320028)the China Postdoctoral Science Foundation(2019TQ0396,China)。
文摘The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death(ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators.Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.
基金supported by grants from the National Natural Science Foundation of China(Nos.31922042 and 81771966)Science,Technology&Innovation Commission of Shenzhen Municipality(No.JCYJ20160531195129079)。
文摘Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side effects.According to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and receptors.Recently,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer therapy.Herein,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug delivery.We summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.
基金supported by the National Natural Science Foundation of China Aerospace Advanced Manufacturing Technology Research Joint Fund(Grant No.U2037203,2020)the Fundamental Research Funds for the Central Universities(Grant No.YCJJ202202010)+1 种基金supported by the State Key Laboratory of Materials Processing and Die&Mould Technology and Analysis and Testing Center,Huazhong University of Science and Technology。
文摘The simultaneous placement of different types of materials including polymers,ceramics,and metals,in their desired positions could be adopted to manufacture end-use devices/apparatuses with diverse functionalities and significantly reduce the fabrication cost and time.However,existing additive manufacturing(AM)approaches can only treat one material species at a time due to their intrinsic working mechanisms.Here we develop an AM manipulator for manufacturing a wide variety of material species,including polymers,ceramics,and metals,through a multifilament transport strategy assisted by laser power.The six-jaw manipulator contains three pairs of filament delivering/cutting systems for transporting diverse materials and a beam of tunable laser as the thermal source.The whole apparatus is integrated into a robotic manipulator to create a multifreedom manufacturing platform.With this innovation,products with multiple material species and desired complex geometries can be fabricated on demand.Furthermore,we synthesize a multimaterial(polymer/ceramic/metal)printed magnetoelectric pressure sensor that can convert applied mechanical forces to electricity and maintain efficiency even after undergoing 10000 cycles of pressure/recovery.With this multimaterial filament transport and laser manufacturing strategy,our AM manipulator exhibits promising application in the advanced manufacturing of embedded electronics,sensors,soft robotics,and customizable medical devices.
基金The authors gratefully acknowledge the support of this research by the National Natural Science Foundation of China(31922042,81971737,32171313)Guangdong Basic and Applied Basic Research Foundation(2020B1515020017,China)+4 种基金Shenzhen Science and Technology Program(RCYX20210706092104033,China)Science and Technology Innovation Committee of Shenzhen Municipality(JCYJ20190807152601651,China)Guangdong Special Support Program(2019TQ05Y224,China)the Fundamental Research Funds for the Central Universities(2021-RC310-005,2020-RC320-002 and 2019PT320028,China)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-058,China).
文摘Hydrogen sulfide(H_(2)S)is the most recently discovered gasotransmitter molecule that activates multiple intracellular signaling pathways and exerts concentration-dependent antitumor effect by interfering with mitochondrial respiration and inhibiting cellular ATP generation.Inspired by the fact that H_(2)S can also serve as a promoter for intracellular Ca^(2+)influx,tumor-specific nanomodulators(I-CaS@PP)have been constructed by encapsulating calcium sulfide(CaS)and indocyanine green(ICG)into methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PLGA-PEG).I-CaS@PP can achieve tumor-specific biodegradability with high biocompatibility and pH-responsive H_(2)S release.The released H_(2)S can effectively suppress the catalase(CAT)activity and synergize with released Ca^(2+)to facilitate abnormal Ca^(2+)retention in cells,thus leading to mitochondria destruction and amplification of oxidative stress.Mitochondrial dysfunction further contributes to blocking ATP synthesis and downregulating heat shock proteins(HSPs)expression,which is beneficial to overcome the heat endurance of tumor cells and strengthen ICG-induced photothermal performance.Such a H_(2)S-boosted Ca^(2+)-involved tumor-specific therapy exhibits highly effective tumor inhibition effect with almost complete elimination within 14-day treatment,indicating the great prospect of CaS-based nanomodulators as antitumor therapeutics.
基金financially supported by the National Natural Science Foundation of China(No.52105341)the China Postdoctoral Science Foundation(No.2020M682406)+4 种基金Post-Doctoral Innovative Research Post of Hubei Province(No.257963)the Fundamental Research Funds for the Central Universities(Nos.2019kfyRCPY044and 2021GCRC002)the Program for HUST Academic Frontier Youth Team(No.2018QYTD04)the Guangdong Provincial Enterprise Key Laboratory for 3D Printing Polymer and Composite Materials(No.2018B030323001)the Wenzhou Industrial Science and Technology Project(No.ZG2020048)。
文摘Porous structure design on the contact surface is crucial to promote the osseointegration of the intervertebral cage while preventing subsidence and displacement.However,the stress response will undergo significant changes for the current random porous cages,which can directly affect the mechanical properties and long-term usability.Here,this paper proposed a newly designed polyetheretherketone(PEEK)cage with the triply periodic minimal surface(TPMS)-structured lattice surfaces to provide tailored 3 D microporosity and studied the mechanical performance,stress/strain responses,and microstructure changes in depth.The lattice-surfaced PEEK cage mainly exhibits a multiple-point-plane stress transfer mechanism.The compression modulus and elastic limit can be adjusted by controlling the area of the Diamond TPMS surface while the energy absorption efficiency remains stable.The microstructure of high-strength PEEK is featured by the radial pattern morphology.Meanwhile,the double-stranded orthorhombic phase is more ordered,and the benzene plane subunit and lattice volume become more expanded.
文摘目的:探讨胃癌病人淋巴结转移率分组界值及其对预后的评估。方法:回顾性分析2004年1月至2008年7月复旦大学附属中山医院392例行胃癌根治术,分期为美国癌症联合委员会(American Joint Committee on Cancer,AJCC)(第8版)Ⅱ~Ⅲ期的病人。利用X-tile软件进行淋巴结转移率的分组,评估淋巴结转移率与其他临床病理因素的相关性和对病人预后的评估。建立列线图预测模型,绘制校准曲线,与实际作比较。用Bootstrap法进行内部验证,计算一致性指数(C-index)评估模型准确性。结果:X-tile获得淋巴结转移率的最佳截断值为0.20(20%)和0.70(70%)。将淋巴结转移率分为1组(0~20%)、2组(21%~69%)和3组(70%~100%)。3组病人的生存差异有统计学意义(P<0.001)。单因素分析显示,淋巴结转移率、TNM分期、T分期、N分期、淋巴管浸润和年龄是影响预后的相关因素。多因素分析显示,淋巴结转移率、T分期、N分期、淋巴管浸润及年龄是影响预后的独立因素。分别以淋巴结转移率、TNM分期、淋巴管浸润及年龄绘制病人总体生存率的受试者操作特征曲线,其曲线下面积分别为0.699、0.667、0.587、0.561。采用淋巴结转移率、TNM分期、淋巴管浸润和年龄构建列线图预测模型,其C-index为0.707(95%CI:0.705~0.708)。校正曲线显示的1、3及5年预测生存率与实际相符。结论:淋巴结转移率是影响Ⅱ~Ⅲ期胃癌根治术后病人生存的独立危险因素。在判断Ⅱ~Ⅲ期胃癌根治术后病人预后时,淋巴结转移率是N分期的有效补充,可指导合理治疗。
