Infrared Responsive Choline Phosphate Lipids for Synergistic Cancer Therapy

Choline phosphate lipids have been designed and developed as new-generation zwitterionic nanocarriers with excellent biocompatibility and bioorthogonality to provide a more programmable performance for cancer therapy. However, there is a lack of spatiotemporal and reversible control for drug release at target tumor cells, which can lead to severe adverse effects to normal tissue and discounted treatment outcome. Here, light-inducible Lip-cRGDfk/ICG/Dox liposomes were developed for synergistic cancer therapy. ICG can effectively convert light energy into selective heating in a local environment upon laser irradiation, thus inducing thermal ablation of tumor cells, and further reversibly trigger the spatiotemporal release of anticancer drugs (Dox) at tumor cells due to the conformation transformation of CP lipids to synergistically kill tumor cells. That Lip-cRGDfk/ICG/Dox exhibited a significant improvement for breast cancer therapy in vitro and in vivo is also demonstrated, thus it can serve as an efficient platform to noninvasively and spatiotemporally control the activation of cytotoxicity at tumor cells for precision cancer therapy.     

锌在食管癌变中的作用

应用日立１８０－３０型原子吸收火焰分光光度计，对３６例食管癌组织中的微量元素锌进行了测定，并与３０例食管癌患者的癌旁正常食管组织和１２例正常人的食管组织进行了对照比较，结果表明：癌组织锌含量明显低于癌旁组织和正常食管组织锌含量，癌旁组织锌含量又显著低于正常食管组织锌含量，有淋巴结转移和恶性程度高的食管癌组织中锌含量明显减少，提示锌缺乏时可以诱发食管癌，在食物中补充锌等能预防食管癌的发生。     

影响白砂糖色值测量结果的原因探讨

研究了水质、滤膜、溶液浓度、糖液ｐＨ值、混浊度的变化与白砂糖色值的关系。研究结果表明，溶液的ｐＨ变化影响最严重。不调整糖液ｐＨ与用ＨＣｌ或ＮａＯＨ调整糖液ｐＨ对比所得白砂糖色值的结果是满意的。标准偏差１１２～１８６，相对标准偏差１１６％～２２５％，调ｐＨ使结果偏高，导致产生系统误差。因此：测定白砂糖色值不宜调整糖液的ｐＨ。     

Characteristics of electroosmotic flow and migration of neutral solutes under stepwise gradient elution of capillary electrochromatography

A theoretical study on the velocity of electroosmotic flow (EOF) and the retention times of neutral solutes under multiple-step gradient of capillary electrochromatography (CEC) was carried out, focusing on that with three kinds of mobile phases. Through the model computations, the detaining time of the second kind of mobile phase in the column was proved to play an important role in affecting EOF. The variation speed of EOF was shown to be determined by the differences among dead times in different steps. In addition, the prediction of the retention times of 13 aromatic compounds under gradient mode was performed with the deduced equations. A relative error below 3.3% between the calculated and experimental values was obtained, which demonstrated the rationality of the theoretical deduction. Our study could not only improve the comprehension of stepwise gradient elution, but also be of significance for the further optimization of separation conditions in the analysis of complex samples.     

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Fifteen organometallic Ir(III) half‐sandwich complexes ( 1A – 5C ) having the general formula [(η⁵‐Cp^x)Ir(N^N)Cl]PF₆ (Cp^x = Cp*, tetramethyl(phenyl)cyclopentadienyl (Cp^xph) or tetramethyl(biphenyl)cyclopentadienyl (Cp^xbiph); N^N = diamine) have been synthesized and characterized. The molecular structure of 1A was determined using single‐crystal X‐ray diffraction analysis. The hydrolysis of 1A – 5C was monitored using UV–visible spectra. Complexes 3A – 3C showed catalytic activity for the oxidation of NADH to NAD⁺, where 3C showed the highest turnover number of 29.9 within 450 min. Cytotoxicity examination by MTT assay was carried out against two human cancer cell lines (HeLa and A549) after 24 or 48 h drug treatment. The complexes showed high potency, where the most potent complex ( 3C ; IC₅₀ = 3.4 μM) was six times more active than cisplatin against A549 cells after 24 h drug exposure. Cytotoxic potency towards A549 cells increased with phenyl substitution on Cp ring: Cp^xbiph > Cp^xph > Cp*. In addition, the biological studies showed that 3C caused cell apoptosis and cell cycle arrest at G₁ phase in A549 cancer cells. Moreover, 3C increased the level of reactive oxygen species markedly after 24 h, which may provide an important basis for killing cancer cells. Confocal laser scanning microscopy was used to track 3C in A549 cells. The cellular localization experiment showed that 3C targeted lysosomes and caused lysosomal damage.     

基于DNA的细胞膜功能化

细胞膜在细胞与外界环境间的物质运输、能量转换和信息传递等过程中起着重要作用,研究和控制细胞膜上的分子的相互作用,对理解和操控细胞的生理功能具有重要意义。脱氧核糖核酸(Deoxyribonucleic acid, DNA)分子具有精确自组装和可编程的特性,是一种研究生物膜分子相互作用的新工具。本综述中,我们概括了DNA分子修饰细胞膜的方法,随后介绍了基于DNA分子的监测、控制细胞膜分子相互作用的工作以及DNA分子介导细胞连接的研究,并分析了上述研究的局限性。最后,我们对基于DNA的细胞膜功能化研究进行总结与展望,以期促进对细胞膜功能的新认识,获得控制细胞功能的新方法。     

In Situ Observation of Dynamic Galvanic Replacement Reactions in Twinned Metallic Nanowires by Liquid Cell Transmission Electron Microscopy

Galvanic replacement is a versatile approach to prepare hollow nanostructures with controllable morphology and elemental composition. The primary issue is to identify its fundamental mechanism. In this study, in situ liquid cell transmission electron microscopy was employed to monitor the dynamic reaction process and to explore the mechanism of galvanic replacement. The detailed reaction process was revealed based on in situ experiments in which small Au particles first appeared around Ag nanowires; they coalesced, grew, and adhered to Ag nanowires. After that, small pits grew from the edge of Ag nanowires to form tubular structures, and then extended along the Ag nanowires to obtain hollowed structures. All of our experimental observations from the viewpoint of electron microscopy, combined with DFT calculations, contribute towards an in‐depth understanding of the galvanic replacement reaction process and the design of new materials with hollow structures.     

Programmable Live-Cell CRISPR Imaging with Toehold-Switch-Mediated Strand Displacement

The widespread application of CRISPR-Cas9 has transformed genome engineering. Nevertheless, the precision to control the targeting activity of Cas9 requires further improvement. We report a toehold-switch-based approach to engineer the conformation of single guide RNA (sgRNA) for programmable activation of Cas9. This activation circuit is responsive to multiple inputs and can regulate the conformation of the sgRNA through toehold-switch-mediated strand displacement. We demonstrate the orthogonal suppression and activation of Cas9 with orthogonal DNA inputs. Combination of toehold switches leads to a variety of intracellular Cas9 activation programs with simultaneous and orthogonal responses, through which multiple genome loci are displayed in different colors in a controllable manner. This approach provides a new route for programing CRISPR in living cells for genome imaging and engineering.     

UV‐Irradiation Cured Organic‐inorganic Hybrid Nanocomposite Initiated by Ethoxysilane‐modified Multifunctional Polymeric Photoinitiator through Sol‐gel Process

The UV‐cured organic‐inorganic hybrid nanocomposite (nano‐Si‐m‐PI) was prepared through the photopolymerization of acrylic resin initiated by ethoxysilane‐modified multifunctional oligomeric photoinitiator (Si‐m‐PI). The esterification reaction of 2‐hydroxy‐4′‐(2‐hydroxyethoxy)‐2‐methylpropiophenone (Irgacure 2959) with thioglycolic acid, and the following addition reactions with dipentaerythritol hexaacrylate and then 3‐aminopropyltriethoxysilane were carried out for preparing the Si‐m‐PI. The Si‐m‐PI exhibits the similar UV absorption and molar extinction coefficient with Irgacure 2959. The photoinitiating activity study by photo‐DSC analysis showed that the Si‐m‐PI possesses high photopolymerization rate at the peak maximum (R_p^max) and final unsaturation conversion (P^f) in the cured hybrid films. From the scanning electron microscope (SEM) observation, the SiO₂ nanoparticles dispersed uniformly in the formed nano‐Si‐m‐PI, whereas the aggregation of nanoparticals occurred in nano‐Irg, which was prepared through the photopolymerization of acrylic resin initiated by Irgacure 2959. Moreover, compared with the UV‐cured pure polymer and nano‐Irg, the nano‐Si‐m‐PI showed remarkably enhanced thermal stability and mechanical properties.     

High throughput tryptic digestion via poly (acrylamide-co-methylenebisacrylamide) monolith based immobilized enzyme reactor

A poly (acrylamide-co-methylenebisacrylamide) (poly (AAm-co-MBA)) monolith was prepared by thermal polymerization in the 100 or 250 μm i.d. capillary. The monolithic support was activated by ethylenediamine followed by glutaraldehyde. Trypsin was then introduced to form an immobilized enzyme reactor (IMER). The prepared IMER showed a reliable mechanical stability and permeability (permeability constant K = 2.65 × 10⁻¹³ m²). With BSA as the model protein, efficient digestion was completed within 20 s, yielding the sequence coverage of 57%, better than that obtained from the traditional in-solution digestion (42%), which took about 12 h. Moreover, BSA down to femtomole was efficiently digested by the IMER and positively identified by matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). To test the applicability of IMER for complex sample profiling, proteins extracted from Escherichia coli were digested by the IMER and further analyzed by nanoreversed phase liquid chromatography-electrospray ionization-mass spectrometry (nanoRPLC-ESI-MS/MS). In comparison to in-solution digestion, despite slightly fewer proteins were positively identified at a false discovery rate (FDR) of ∼1% (333 vs 411), the digestion time used was largely shortened (20 s vs 24 h), implying superior digestion performance for the high throughput analysis of complex samples.