摘要：Persistent luminescence nanoprobes (PLNPs) can remain luminescent after ceasing *** to the ultra-long decay time of persistent luminescence (PersL),autofluorescence interference can be efficiently eliminated by collecting PersL signal after autofluorescence decays completely,thus the imaging contrast and sensing sensitivity can be significantly *** near-infrared (NIR) light shows reduced scattering and absorption coefficient in penetrating biological organs or tissues,near-infrared persistent luminescence nanoprobes (NIR PLNPs) possess deep tissue penetration and offer a bright prospect in the areas of in vivo biosensing/*** this review,we firstly summarize the design of different types of NIR PLNPs for biosensing/bioimaging,such as transition metal ions-doped NIR PLNPs,lanthanide ions-doped NIR PLNPs,organic molecules-based NIR PLNPs,and semiconducting polymer self-assembled NIR ***,organic molecules-based NIR PLNPs and semiconductor self-assembled NIR PLNPs,for the first time,were introduced to the review of ***,the effects of different types of charge carriers on NIR PersL and luminescence decay of NIR PLNPs are significantly emphasized so as to build up an in-depth understanding of their luminescence *** includes the regulation of valence band and conduction band of different host materials,alteration of defect types,depth and concentration changes caused by ion doping,effective radiation transitions and energy transfer generated by different luminescence *** the design and potential of NIR PLNPs as long-lived luminescent materials,the current challenges and future perspective in this rapidly growing field are also discussed.

摘要：Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411,and a replaceable anti-biomarker probe(ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS 1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.

摘要：Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.

摘要：核酸适体是通过体外筛选技术得到的可特异性结合靶标分子的单链寡核苷酸分子探针,其表现出与抗体相当或更优异的特异性和亲和力,且具有靶标范围广、免疫原性低、易于精准制备和修饰及设计灵活可控等优势.为癌症的早期筛查、诊断及靶向治疗提供了全新的分子工具,在癌症诊疗领域获得了广泛的关注与应用.本文聚焦核酸适体在癌症诊断及治疗中的应用,对近年来取得的研究进展进行了系统性总结,并对未来发展方向及前景进行了展望.

摘要：目的:建立一种快速、简便且无需核酸提取的泰国型α缺失地中海贫血的快速基因诊断方法及其在产前诊断中应用。方法:设计可以扩增α-珠蛋白基因簇中--THAI等位基因的特征序列引物组,直接以待测样本为模板,不需要核酸提取,进行聚合酶链反应(PCR)直接扩增,扩增产物进行琼脂糖凝胶电泳即可分析结果。结果:成功建立泰国缺失型地中海贫血的快速基因诊断方法,并且直接以全血、羊水、干血斑、脐带血为模板进行扩增的结果与常规跨越断裂点聚合酶链反应(gap-PCR)技术确定基因型完全一致。结论:该法不需要提取核酸,减少操作步骤与实验室污染、节约成本、快速、准确,可作为常规方法用于临床样品的地中海贫血分子基因检测及巴氏水肿胎和缺失型HbH病的产前诊断及泰国型α-地中海贫血的产前诊断新方法。

摘要：生物医药产业正以前所未有的速度发展,其研发数字基础设施体系的建设和完善是国家生物科技创新和健康中国建设的重要基石。本文论述了生物医药研发数字基础设施的内涵与新时期生物医药研发数字基础设施的分类和系统体系;总结了美国、欧盟和我国生物医药研发数字基础设施战略布局的现状及发展路径,梳理了我国生物医药研发数字基础设施建设在国际影响力和权威性、发展模式设计和效能、可持续建设、管理组织架构建设方面与欧美国家存在的差距及在顶层设计、管理治理方面面临的挑战。研究建议,加强生物医药研发数字基础设施顶层设计,加强生物医学和健康医疗资源的统筹编排,加强单一个体平台集群化整合建设和治理,加强开放平台能力建设和运营保障。

摘要：500T压力铸铝模具设计时,通过对上、下模增设排气槽及下模进铝口的合理布置,保证了在整个压铸的短暂瞬间的排气及进铝量,另外还通过使用梅花形筋板式假轴有效降低了模具的成本。压铸过程中通过对铝液清化、铝水温度、慢压射时间、压射力等多种工艺参数的严格控制保证了铸铝转子的压铸质量。

摘要：通过对大批量定制生产模式下的需求产品配置技术的研究,提出了产品族需求类和需求匹配模板的概念,建立了相应的需求产品模型以及基于实例的需求产品配置模型,采用二级相似性匹配的方法,得到需求产品的配置结果,并分析了配置方法对需求响应的影响。配置方法在电梯的需求产品配置响应中得到了应用。

摘要：针对薄壁件铣削过程加工误差预测,建立了一种快速有效的材料去除仿真模型,即利用工件的原始有限元网格模型,直接使用径向切削量的名义值进行材料去除效应模拟,将被切除网格单元的单元刚度按被切除体积与该单元初始体积的百分率等效修正。该模型既无需进行工件网格重划,又可以很好地保证仿真精度,极大地简化了处理流程,提高了计算效率。应用实例的计算结果和试验结果比较,表明了该模型的有效性和实用性。

摘要：为了实现无人艇在复杂的海洋环境下能够顺利地躲避障碍物,并按照相应的设计路线进行自主航行的目的,完成了一种基于多线激光雷达的海上无人艇软硬件设计。利用多线激光雷达获得周围环境中的连续数据和无人艇实时的位姿信息,建立无人艇所在位置的坐标系,对无人艇周围环境中的障碍物点云数据进行过滤、聚类和分割处理。在角度与距离上同时对障碍物进行分类,判断每个角度中障碍物的占比是否小于预设阈值,使用改进的A*算法对无人艇路径进行规划,使无人艇按照规定的路线航行。