基于Cy7类菁染料分子探针的设计策略

菁染料是一类经典的荧光染料母核, 具有摩尔消光系数大、 吸收波长可调、 溶解性良好及生物兼容性好等优点, 被广泛用于蛋白标记、 痕量金属离子检测、 生物活性物质检测、 细胞和活体成像及肿瘤靶向治疗等领域. 近年来, 生物医学领域对活体结构及功能成像深度提出更高的需求, 基于优异的长波长染料母核开发近红外荧光分子探针逐渐成为领域的研究重点. 吲哚七甲川菁染料(Cy7)是一类最具代表性的菁染料, 本文重点综合评述了自1992年以来基于Cy7结构开发的分子探针, 并介绍了该类荧光探针的设计策略. 最后, 讨论了该领域研究面临的挑战, 并对未来的发展方向进行了总结和展望.     

RNA切割型脱氧核酶在致病菌检测中的研究进展

脱氧核酶是通过体外筛选技术得到的具有催化功能的单链寡核苷酸分子. 随着体外筛选技术的发展, 越来越多的脱氧核酶被筛选出来. 其中, 靶向细菌的具有RNA切割作用的脱氧核酶(RNA-cleaving DNAzyme, RCD)同时拥有分子识别和催化RNA裂解的功能, 且具有设计灵活、 易于制备和修饰、 成本低廉等优势, 在致病菌检测领域获得了广泛的关注和应用, 为致病菌的早期发现和预防提供了全新的分子工具. 本文系统总结了RCD在致病菌检测中的研究和应用, 并对其面临的问题和未来发展前景进行了展望.     

长余辉纳米材料的控制合成及在疾病诊断中的应用

长余辉纳米材料具有独特的发光性质, 能在激发光关闭后持续发光. 通过收集激发光关闭后的长余辉发光信号可以有效消除背景信号的干扰. 此外, 长余辉材料在成像时无需原位激发, 可以减少生物体系的组织自发荧光和光散射干扰, 提高生物成像和检测的灵敏度. 由于这种独特的光学特性, 长余辉纳米材料在生物传感/生物成像以及疾病治疗等领域被广泛应用. 近年来, 为满足疾病相关生物标志物的体外检测及体内生物成像的应用要求, 控制合成发光性能优异、 生物相容性好的长余辉纳米材料成为研究热点.     

Prostatic Zn determination for prostate cancer diagnosis

We present our studies of prostatic Zn concentration measurements, carried out in the light of a novel prostate cancer (CAP) diagnosis method proposed by us. The method is based on in vivo prostatic Zn mapping by XRF trans-rectal probe.

We report on the extensive clinical studies, intended to assess the validity of the novel proposed diagnostic method. Zn content was measured in vitro in needle-biopsy samples from several hundreds of patients, and was correlated with histological findings and other patient parameters. For this purpose, a technique of absolute Zn content determination in 1 mm³ fresh tissue samples by XRF was developed. The experimental details and the main clinical-evaluation results are presented.

We further outline the suggested design of the XRF trans-rectal probe for an efficient in vivo detection and mapping of the Zn fluorescence radiation from the prostate through the rectal wall. Laboratory phantom studies, a preliminary design concept and its expected performance are also reported.     

磷脂管的体外组装及其在生物与化学领域的研究进展

由磷脂组成的微管结构在有机体组织及器官中均有存在，在细胞间的物质传递及信息交流等方面起着重要作用。实现磷脂管在体外的简单快速组装是解析生命信息系统的良好途径。由于良好的生物相容性及支架结构特性，对磷脂管进行材料或结构修饰，是扩大其潜在应用的极佳手段。以磷脂管本身为载体以及以磷脂管为模板修饰构建的微纳米材料，在生物、材料及化学等方面的应用也取得了一系列成果。对磷脂管的体外组装及其在多个领域的应用研究进行了梳理归纳，重点对磷脂管的体外组装方式以及磷脂管在生物及化学等领域的应用等做了分类阐述与总结，并提出磷脂管在多功能纳米复合材料方面的未来发展及应用方向。     

稀有原人参二醇型皂苷的人肠道菌群生物转化

利用高分离度液相色谱-四极杆飞行时间质谱(RRLC-Q-TOF MS)和超高效液相色谱-三重四极杆质谱(UPLC-QQQ MS)定性定量分析了稀有原人参二醇型皂苷Rd, F₂, Rg₃, CK和Rh₂在离体人肠道菌群中的生物转化过程. 并将上述二醇型皂苷与人肠道菌群在体外厌氧, 37 ℃下共温孵育, 采用电喷雾质谱在负离子模式进行检测, 鉴定代谢产物, 监测其含量变化, 拟合代谢路径. 结果表明, 人参皂苷Rd主要被代谢为F₂, Rg₃, CK, Rh₂和PPD; 人参皂苷F₂主要被代谢为CK和PPD; 人参皂苷Rg₃主要被代谢为Rh₂和PPD; 人参皂苷CK和Rh₂主要被代谢为PPD. 在离体条件下, 人参皂苷Rd, F₂和Rg₃会被肠道菌群完全转化为其代谢产物, 而人参皂苷CK和Rh₂则不能被肠道菌群完全转化为其代谢产物. 原人参二醇型皂苷在人肠道菌群中的主要转化为脱糖基反应, 单糖苷和苷元是稀有原人参二醇型皂苷在人体内发挥药效的物质基础.     

蛋白质微阵列芯片在临床分析中的应用

蛋白质微阵列芯片能够高通量监测生物毒素、分析宿主-微生物相互作用和抗原-抗体相互作用、筛选疾病生物标志物,因此有望成为体外诊断的主要技术之一并在病原体感染、自身免疫性疾病、神经退行性疾病和癌症等疾病的精准医疗中发挥重要作用。 本文通过对最近发表的相关研究成果分析,总结了蛋白质微阵列芯片在临床分析中新进展,分析了其在实际应用中所面临的技术挑战并探讨了相应的解决方案。     

二维层状钴铁双氢氧化物用于癌症协同光治疗

癌症的光子疗法是一种选择性治疗新技术,近几年得到迅猛的发展,该疗法拥有创伤小、选择性好且毒性低、无耐药性等优点。 我们采用水热合成法制备了一种新型的层状钴铁双氢氧化物纳米片(Co-Fe-LDH),利用其具有较大比表面积、稳定高、生物相容性好等的特点,负载光敏剂IR783(LDH-IR783),在近红外激光的刺激下实现癌症的光热光动力协同光治疗。 对所合成的Co-Fe-LDH进行了组成、形貌、光学性质、活性氧(ROS)生成、热量释放等表征,并在细胞及活体水平进行抗癌测试。 实验结果表明,所制备的纳米复合物具有稳定的结构、高IR783负载率以及良好的分散性,并且,在近红外光源照射下表现出优异的光热/光动力效应,能够快速产生大量的活性氧,迅速地释放热量,产生显著的光毒性,能够有效地诱导HeLa细胞的凋亡。 体内抗癌实验表明,所制备的纳米复合物有效地抑制了实体肿瘤的生长,并且未对正常组织产生明显的损伤,毒副作用较低。 这些初步结果将为光热/光动力协同纳米粒子的设计和应用提供新的思路。     

电解水催化材料动态构效关系的原位拉曼研究进展北大核心CSCD

可再生能源电解水产氢对于实现碳中和目标和未来可持续社会的发展具有重要意义。然而,在电解水服役过程中,催化材料往往会发生复杂的结构演变,这对深入理解电解水催化材料反应机制和精准设计高效催化材料造成了挑战。原位电化学拉曼表征技术对催化材料结构动态演变过程的实时监测,是揭示电解水材料动态构效关系,解析催化反应机理的关键。本文介绍了原位电化学拉曼表征技术的基本原理,重点综述了其在催化材料相结构演变、表面活性位点和界面水分子行为中的最新进展,阐述了电解水催化材料在服役过程中结构演变与性能演变之间的变化规律,为实现催化材料全生命周期动态构效关系的精准构建提供了技术基础。最后,分析总结了原位电化学拉曼表征技术在电解水应用过程中存在的问题与挑战,并对先进原位电化学拉曼技术未来的发展进行了展望。     

Synthesis and bioactivities of steroid derivatives as antifungal agents

A series of lanosterol and cholesterol derivatives with modified side chain structures, which might interfere with sterol C24-methyltransferase in the ergosterol biosynthesis as substrate analogs, have been synthesized. The in vitro bioassay studies have shown that some of these compounds, in particular with C24-amino- and thio-functionalities, possess potent antifungal activities, in vivo. Bioassays have also been carried out for the leading compounds.     

卵磷脂类液晶乳液的性能

以卵磷脂为主乳化剂制备了一款液晶乳液。 该乳液在皮肤上具有良好的稳定性能,在皮肤表层停留6 h仍能保持完整的液晶结构,克服了一般液晶乳液中液晶织构无法在皮肤上长时间停留的问题。 液晶结构在皮肤温度范围内具有较高的稳定性,可为液晶乳液其他性能的发挥提供条件。 基于此,我们采用体外称重法研究了液晶乳液的锁水性,发现液晶乳液锁水性能明显优于传统乳液,实验7 h后仍能保持原有水分总质量的50%;体外透析实验证实,液晶乳液表现出显著的缓释性能且能释放完全,7 h后目标分子(水杨酸钠)释放率可达96%;耐温性能研究表明,液晶乳液耐高温性能及低温冻融性能优良,且温度对乳液中层状液晶的影响是可恢复的;采用离心法、高低温循环和高低温长时间(3个月)放置的方法探究了乳液储运稳定性,结果表明,液晶乳液产品储运稳定性极佳,便于实际的应用和储运。 该研究不仅可为开发多效的高端化妆品提供必要信息和参考数据,而且有望拓展卵磷脂类液晶乳化剂体系的应用范畴。     

ICG and Sunitinib-loaded NH2-MOFs for Folate-mediated Hepatocellular Carcinoma Dual-modal Therapy

This research investigated a novel folic acid(FA)-modified zirconium core metal-organic framework(MOF) Uio-66 as a nanocarrier to deliver indocyanine green(ICG) and Sunitinib to cancer cells for combination therapy. Platinum-loaded Uio-66 nanoparticles(Pu) were synthesized via a one-pot method, followed by the modification with FA on their surfaces. This afforded FPu that enabled subsequent loading of ICG and Sunitinib to achieve dual-modal cancer therapy. Drug loading/release test and singlet oxygen detection were also conducted in vitro, and the nanoparticles showed considerable drug loading efficiency for both ICG and Sunitinib, coupled with a high singlet oxygen generation rate. Specifically, drug loading and encapsulation efficiency of Sunitinib were 2.30% and 72.67%, while those for ICG were 2.87% and 90.28%, respectively. Additionally, cytotoxicity test on HepG2 human hepatocellular carcinoma cancer cell line revealed that the fully functional nanoparticles possess excellent biocompatibility and as such could be further investigated as a potential drug delivery system for effectual carcinoma cancer treatment.     

Bacteriochlorophyll-a as photosensitizer for photodynamic treatment of transplantable murine tumors.

Bacteriochlorophyll-a (bChla), which absorbs light of 780 nm wavelength, was tested for in vivo photodynamic activity in the SMT-F and RIF transplantable mouse tumor systems. High performance liquid chromatography (HPLC) analysis of tissue extracts showed that bChla was rapidly degraded in vivo to bacteriopheophytin-a (bPheoa) and other breakdown products. These were also photodynamically active, and tumor response could be achieved over a wavelength range of 660 to 780 nm, while tumor cure was restricted to wavelengths of 755 (bPheoa) to 780 nm. A photosensitizing product absorbing at 660 nm was also present in isolated tumor cells. Photodynamic cell kill of tumor cells isolated from tumors after bChla accumulation in vivo, using 755 or 780 nm light _vitro, was exponential up to 20–40 J cm⁻². Above this light dose little or no further damage could be achieved, which is an indication of the rapid photobleaching of these sensitizers. In vivo, vascular occlusion occurred readily if light treatment was delivered shortly after sensitizer administration, but was delayed if light treatment was carried out 24 h after injection. Although up to 70% of tumor cells were lethally damaged after completion of in vivo light treatment, concurrent severe vascular destruction seemed necessary for tumor cure. Normal tissue photosensitivity totally subsided within 5 days after sensitizer administration.     

细菌感染成像的研究进展

由致病菌或条件致病菌侵入机体繁殖而产生的毒素和其它代谢产物所引起的感染性疾病是目前全球范围内的主要死亡原因之一. 感染性疾病的早期诊断是对其进行有效治疗与控制的重要途径. 分子影像技术的快速发展给体内细菌感染的评估带来了前所未有的变化和机遇. 本文综合评述了计算机断层扫描、 正电子发射断层扫描、 超声成像、 磁共振成像、 荧光成像及光声成像等成像方式在细菌感染体内成像中的研究进展、 不足和发展方向等, 以期为活体细菌感染检测方法的发展提供参考.     

A novel polyethyleneimine-decorated FeOOH nanoparticle for efficient siRNA delivery

Despite the promising prospect of small interfering RNA(siRNA) for the treatment of diverse diseases,it remains challenging to develop novel delive ry materials to desired tissues and cells.In this study,a novel iron oxyhydroxide(FeOOH) nanoparticle(NP) whose surface was modified with branched polyetherimide(PEI) was developed to deliver siRNA into the cancer cells.It was demonstrated that PEI-FeOOH(PFeOOH) efficiently complexed siRNA,mediated effective cellular uptake and endosomal escape,thereby triggering robust gene silencing in vitro.In addition,PFeOOH/siRNA formulation loading with anti-RRM2 siRNA effectively inhibited the growth of tumor tissues,and exhibited excellent safety profiles in vivo.Therefore,this study conceptually provided a FeOOH-based nucleic acid delivery vesicle which can potentially use to achieve diagnosis and therapy simultaneously.     

胺解改性聚L-谷氨酸苄酯引导骨再生膜的制备

以聚L-谷氨酸苄酯(PBLG)为原料, 通过溶剂浇铸与粒子沥滤法分别构建PBLG单层致密和PBLG单层多孔膜, 利用乙醇胺对薄膜表面改性, 构筑双层引导骨再生膜. 研究了不同胺解改性时间对PBLG-s-PHEG双层膜亲水性和力学性能的影响, 结果表明, 随着PBLG分子量的增大, 薄膜的力学性能增强而降解速率减缓. 延长胺解改性时间可提高薄膜亲水性和体内外降解速率. 细胞实验结果表明, 双层薄膜的致密结构能够有效阻隔成纤维细胞的侵入, 多孔结构能够支持细胞贴壁黏附和铺展. 体外生物活性评价结果表明, 表面改性的PBLG基材料可用于体内骨缺损修复. 本文所构建的双层引导骨再生膜在体外具有良好的力学性能和降解性能, 与组织具有一定的贴合性, 同时可有效阻碍成纤维细胞侵入, 具有潜在应用价值.     

Extracellular vesicles based electrochemical biosensors for detection of cancer cells: A review

Extracellular vesicles (EVs) derived from cancer cells are considered as ideal biomarker for liquid biopsy in cancer diagnosis, and are stable and abundant. Electrochemical methods for the detection of EVs are preferred over conventional methods such as Western blotting and enzyme-linked immunosorbent assay for their high sensitivity and real-time detection. This article summaries studies proposing the electrochemical methods utilizing immunological and molecular methodologies for detecting EVs derived biomacromolecules such as miRNAs and transmembrane protein for cancer diagnosis. Moreover, the electrochemical detection methods are compared and future prospects for the development of electrochemical methods for EVs detection are concluded.     

高温红外光谱电化学薄层池的制作与表征

为了拓宽光谱电化学研究范围,开展高温下电化学反应过程,本文研制了一种高温红外光谱电化学薄层池(HTC)。 研制的HTC清洗方便,操作简单,适用于水体系和有机体系。 该HTC可在室温至373 K(根据溶剂沸点,控温精度为±0.5 K)温度范围内使用,具有良好的电化学性能,红外光谱采集谱图清晰信噪比好。 利用铁氰化钾水溶液和对苯醌离子液体溶液的红外光谱电化学行为对HTC进行了表征,得到较满意的结果。     

Multivalent Aptamer-modified DNA Origami as Drug Delivery System for Targeted Cancer Therapy

In spite of great development in nanoparticle-based drug delivery systems(DDSs)for improved therapeutic efficacy,it remains challenging for effective delivery of chemotherapeutic drugs to targeted tumor cells.In this work,we report a triangle DNA origami as targeted DDS for cancer therapy.DNA origami shows excellent biocompatibility and stability in cell culture medium for 24 h.In addition,the DNA origami structures conjugated with multivalent aptamers enable for efficient delivery of anticancer drug doxorubicin(Dox)into targeted cancer cell due to their targeting function,reducing side effects associated with nonspecific distribution.Moreover,we also demonstrated that the multivalent aptamer-modified DNA origami loading Dox exhibits prominent therapeutic efficacy in vitro.Accordingly,this work provides a good paradigm for the development of DNA origami nanostructure-based targeted DDS for cancer therapy.     

昆虫信息素缓释技术的研究进展

昆虫信息素是一类由昆虫个体释放于体外来调节或诱发同种其它个体行为与反应的化学物质。 近年来,应用昆虫信息素防治虫害是当前有机农业绿色防控的新技术之一。 与传统农药防治虫害相比,信息素具有高效、无毒、不产生抗药性以及对天敌无害的特点。 此外,昆虫信息素通常易降解且挥发性高。 因此,基于信息素的缓释技术引起了科研工作者的广泛关注,是涵盖化学、材料与农业的新兴交叉学科。 通过某种特定的方法或技术使昆虫信息素缓慢控制释放,既能有效防治虫害,减少农药使用,提升环境生态水平,同时也能促进区域环境化学品总量与农业成本的降低。 本文详细综述了昆虫信息素缓释技术的最新研究进展并对发展前景进行了展望。