The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidom...The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.展开更多
Figure 6(a)in the paper[Chin.Phys.B 33074203(2024)]was incorrect due to editorial oversight.The correct figure is provided.This modification does not affect the result presented in the paper.
目的探讨欧洲五国(Europe Union Five Countries,EU5)对嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T细胞)治疗产品的卫生技术评估(health technology assessment,HTA)、报销政策的差异及对我国的启示。方法检索EU5国家(...目的探讨欧洲五国(Europe Union Five Countries,EU5)对嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T细胞)治疗产品的卫生技术评估(health technology assessment,HTA)、报销政策的差异及对我国的启示。方法检索EU5国家(英国、法国、德国、意大利、西班牙)HTA机构、报销决策机构及支付方等的官方文件,结合欧洲药品管理局和英国药品和健康产品管理局的数据,分析欧洲主要市场获批的CAR-T细胞治疗产品的HTA评估报告、医保报销决策及定价机制等的差异。结果截至2025年4月,5个国家共有6款CAR-T细胞治疗产品上市,各国在HTA周期和评估结论、报销决策等方面存在差异。英国的初始HTA评估周期最短,平均为9.2个月,通过覆盖与证据开发(coverage with evidence development,CED)机制,利用肿瘤药物基金(Cancer Drug Fund,CDF)为不符合常规准入标准的产品提供临时报销;其二次评估过程基于真实世界证据,周期较长。法国采用患者早期访问政策,HTA周期较短,平均为10.7个月,其HTA结果直接决定CAR-T细胞治疗产品的报销比例及定价策略,并通过CED机制报销;二次评估频率较高,从初次评估到二次评估的时间间隔较短。意大利、西班牙和德国支付体系呈现分散化的特征,且HTA评估与报销决策流程不连续。3个国家均采用按疗效付费(pay for performance,P4P)模式,但在报销触发节点的制定、疗效评价指标的选择、支付机制的设计等方面存在差异,德国实施基于患者生存结局的无效返款模式,而意大利和西班牙采用分期见效付款模式。结论CED与P4P均可有效应对CAR-T细胞治疗产品的高价值与高不确定性。CED通过临时报销同步开展上市后研究,P4P在常规准入中依据疗效节点进行风险分担,二者均以真实世界证据为核心。建议将CED与P4P整合纳入医保准入框架,以动态证据降低决策的不确定性。展开更多
据Zuo Y 2026年2月9日[Cancer Cell,2026,44(2):366-382.e10.]报道,罗斯威尔公园综合癌症中心的一项实验室研究阐述了一种新方法,能够提升嵌合抗原受体(CAR)T细胞疗法在实体瘤中的疗效,从而实现肿瘤的根除。研究人员利用小细胞肺癌的临...据Zuo Y 2026年2月9日[Cancer Cell,2026,44(2):366-382.e10.]报道,罗斯威尔公园综合癌症中心的一项实验室研究阐述了一种新方法,能够提升嵌合抗原受体(CAR)T细胞疗法在实体瘤中的疗效,从而实现肿瘤的根除。研究人员利用小细胞肺癌的临床前模型,评估了一种旨在靶向白细胞介素36γ(IL-36γ)的CAR T细胞的有效性。展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen...多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。展开更多
Multi-functional Al-matrix composites with high volume fraction （55%-57%） of SiC particles are produced with the new pressureless infiltration fabrication technology. X-ray detection and microscopic observation disp...Multi-functional Al-matrix composites with high volume fraction （55%-57%） of SiC particles are produced with the new pressureless infiltration fabrication technology. X-ray detection and microscopic observation display the composites which are macroscopically homogeneous without porosity. The investigation further reveals that the SiC/Al composites possess low density （2.94 g/cm^3）, high elastic modulus （220 GPa）, prominent thermal management function as a result of low coefficient of thermal expansion （8 × 10^4 K^-1） and high thermal conductivity （235 W/（m.K）） as well as unique preventability of resonance vibration. By adopting a series of developed techniques, the multi-functional SiC/Al composites have managed to be made into near-net-shape parts. Many kinds of precision components of space-based optomechanical structures and airborne optoelectronic platform have been turned out. Of them, several typical products are being under test in practices.展开更多
Metal-organic frameworks（MOFs） are a unique class of porous crystalline materials that have shown promise for a wide range of applications. MOFs have been explored as a new type of heterogeneous catalytic materials,...Metal-organic frameworks（MOFs） are a unique class of porous crystalline materials that have shown promise for a wide range of applications. MOFs have been explored as a new type of heterogeneous catalytic materials, because of their high surface area, uniform and tunable pores, facile functionalization and incorporation of catalytic active sites. The use of multi-functional sites MOF materials as catalysts for synergistic catalysis and tandem reactions has attracted increasing attention. In this review, we aim to introduce the construction of bi-or multi-functional MOF catalysts with cooperative or cascade functions via post-synthetic modification（PSM）.展开更多
To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforc...To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforced polymer(CFRP)and aluminum components for a robotic aircraft assembly system.To meet the specific functional requirements for blind rivet installation on CFRP and aluminum materials,additional modules are incorporated on the end effector aside of the basic processing modules for drilling.And all of these processing modules allow for a onestep-drilling-countersinking process,hole inspection,automatic rivet feed,rivet geometry check,sealant application,rivet insertion and installation.Besides,to guarantee the better quality of the hole drilled and joints riveted,several online detection and adjustment measures are applied to this end effector,including the reference detection and perpendicular calibration,which could effectively ensure the positioning precision and perpendicular accuracy as demanded.Finally,the test result shows that this end effector is capable of producing each hole to a positioning precision within ±0.5 mm,aperpendicular accuracy within 0.3°,a diameter tolerance of H8,and a countersink depth tolerance of±0.01 mm.Moreover,it could drill and rivet up to three joints per minute,with acceptable shearing and tensile strength.展开更多
Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmo...Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.展开更多
基金supported by the central government and guides local funds for science and technology development(2022ZY0109).
文摘The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.
文摘Figure 6(a)in the paper[Chin.Phys.B 33074203(2024)]was incorrect due to editorial oversight.The correct figure is provided.This modification does not affect the result presented in the paper.
文摘目的探讨欧洲五国(Europe Union Five Countries,EU5)对嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T细胞)治疗产品的卫生技术评估(health technology assessment,HTA)、报销政策的差异及对我国的启示。方法检索EU5国家(英国、法国、德国、意大利、西班牙)HTA机构、报销决策机构及支付方等的官方文件,结合欧洲药品管理局和英国药品和健康产品管理局的数据,分析欧洲主要市场获批的CAR-T细胞治疗产品的HTA评估报告、医保报销决策及定价机制等的差异。结果截至2025年4月,5个国家共有6款CAR-T细胞治疗产品上市,各国在HTA周期和评估结论、报销决策等方面存在差异。英国的初始HTA评估周期最短,平均为9.2个月,通过覆盖与证据开发(coverage with evidence development,CED)机制,利用肿瘤药物基金(Cancer Drug Fund,CDF)为不符合常规准入标准的产品提供临时报销;其二次评估过程基于真实世界证据,周期较长。法国采用患者早期访问政策,HTA周期较短,平均为10.7个月,其HTA结果直接决定CAR-T细胞治疗产品的报销比例及定价策略,并通过CED机制报销;二次评估频率较高,从初次评估到二次评估的时间间隔较短。意大利、西班牙和德国支付体系呈现分散化的特征,且HTA评估与报销决策流程不连续。3个国家均采用按疗效付费(pay for performance,P4P)模式,但在报销触发节点的制定、疗效评价指标的选择、支付机制的设计等方面存在差异,德国实施基于患者生存结局的无效返款模式,而意大利和西班牙采用分期见效付款模式。结论CED与P4P均可有效应对CAR-T细胞治疗产品的高价值与高不确定性。CED通过临时报销同步开展上市后研究,P4P在常规准入中依据疗效节点进行风险分担,二者均以真实世界证据为核心。建议将CED与P4P整合纳入医保准入框架,以动态证据降低决策的不确定性。
文摘据Zuo Y 2026年2月9日[Cancer Cell,2026,44(2):366-382.e10.]报道,罗斯威尔公园综合癌症中心的一项实验室研究阐述了一种新方法,能够提升嵌合抗原受体(CAR)T细胞疗法在实体瘤中的疗效,从而实现肿瘤的根除。研究人员利用小细胞肺癌的临床前模型,评估了一种旨在靶向白细胞介素36γ(IL-36γ)的CAR T细胞的有效性。
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
文摘多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。
基金Foundation items： High-technology Research and Development Programme of China （2007AA03Z544） Aeronautical Science Foundation of China （20075221001）
文摘Multi-functional Al-matrix composites with high volume fraction （55%-57%） of SiC particles are produced with the new pressureless infiltration fabrication technology. X-ray detection and microscopic observation display the composites which are macroscopically homogeneous without porosity. The investigation further reveals that the SiC/Al composites possess low density （2.94 g/cm^3）, high elastic modulus （220 GPa）, prominent thermal management function as a result of low coefficient of thermal expansion （8 × 10^4 K^-1） and high thermal conductivity （235 W/（m.K）） as well as unique preventability of resonance vibration. By adopting a series of developed techniques, the multi-functional SiC/Al composites have managed to be made into near-net-shape parts. Many kinds of precision components of space-based optomechanical structures and airborne optoelectronic platform have been turned out. Of them, several typical products are being under test in practices.
基金supported by the National Natural Science Foundation of China (Nos. 21371069 and 21621001)
文摘Metal-organic frameworks（MOFs） are a unique class of porous crystalline materials that have shown promise for a wide range of applications. MOFs have been explored as a new type of heterogeneous catalytic materials, because of their high surface area, uniform and tunable pores, facile functionalization and incorporation of catalytic active sites. The use of multi-functional sites MOF materials as catalysts for synergistic catalysis and tandem reactions has attracted increasing attention. In this review, we aim to introduce the construction of bi-or multi-functional MOF catalysts with cooperative or cascade functions via post-synthetic modification（PSM）.
基金supported by the National Natural Science Foundations of China(Nos.5157051626,51475225)
文摘To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforced polymer(CFRP)and aluminum components for a robotic aircraft assembly system.To meet the specific functional requirements for blind rivet installation on CFRP and aluminum materials,additional modules are incorporated on the end effector aside of the basic processing modules for drilling.And all of these processing modules allow for a onestep-drilling-countersinking process,hole inspection,automatic rivet feed,rivet geometry check,sealant application,rivet insertion and installation.Besides,to guarantee the better quality of the hole drilled and joints riveted,several online detection and adjustment measures are applied to this end effector,including the reference detection and perpendicular calibration,which could effectively ensure the positioning precision and perpendicular accuracy as demanded.Finally,the test result shows that this end effector is capable of producing each hole to a positioning precision within ±0.5 mm,aperpendicular accuracy within 0.3°,a diameter tolerance of H8,and a countersink depth tolerance of±0.01 mm.Moreover,it could drill and rivet up to three joints per minute,with acceptable shearing and tensile strength.
基金supported by grants from CAMS Innovation Fund for Medical Sciences(Grant No.:2021-I2M-1-026)Scientific Research Project of Tianjin Education Commission(Grant No.:2020KJ140)Tianjin Health Research Project(Grant No.:KJ20017)。
文摘Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.
