Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice

Phase separation in cell membranes promotes the assembly of transmembrane receptors to initiate signal transduction in response to environmental cues. Many cellular behaviors are manipulated by promoting membrane phase separation through binding to multivalent extracellular ligands. However, available extracellular molecule tools that enable manipulating the clustering of transmembrane receptors in a controllable manner are rare. In the present study, we report a DNA nanodevice that enhances membrane phase separation through the clustering of dynamic lipid rafts. This DNA nanodevice is anchored in the lipid raft region of the cell membrane and initiated by ATP. In a tumor microenvironment, this device could be activated to form a long DNA duplex on the cell membrane, which not only enhances membrane phase separation, but also blocks the interaction between the transmembrane surface adhesion receptor and extracellular matrix, leading to reduced migration. We demonstrate that the ATP-activated DNA nanodevice could inhibit cancer cell migration both in vitro and in vivo. The concept of using DNA to regulate membrane phase separation provides new possibilities for manipulating versatile cell functions through rational design of functional DNA structures.

A DNA nanodevice is developed to enhance the cell membrane phase separation in a tumor microenvironment to weaken the formation of focal adhesion. As a result, the migration of cancer cells is inhibited both in vitro and in vivo.     

蝙蝠喉部发声组织建模及发声机理*

建立蝙蝠发声组织模型对超声机理研究及在智能设备的应用具有重要意义。根据蝙蝠喉部发声组织结构特点,通过有限元方法构建了蝙蝠的3种不同发声组织模型,分析了尺寸、材料力学参数、组织结构和张力4个因素对发声组织特征频率的影响。结果表明,如果用人类声带,按比例缩小构建蝙蝠喉部组织模型,蝙蝠无法发出超声波。构建组织结构含甲状软骨和声带的半鼓状模型和只含声带的条状模型,两种模型的特征频率相近且在合理的参数域内均无法达到超声范围。而含膜条状模型的特征频率可以通过张力进行超声频率的调节,这与文献的实验结果一致。因此,可基于含膜条状模型对蝙蝠喉管发声组织进行建模及其发声机理研究。     

A molecular mechanics approach for analyzing tensile nonlinear deformation behavior of single-walled carbon nanotubes

In this paper, by capturing the atomic information and reflecting the behaviour governed by the nonlinear potential function, an analytical molecular mechanics approach is proposed. A constitutive relation for single-walled carbon nanotubes (SWCNT’s) is established to describe the nonlinear stress-strain curve of SWCNT’s and to predict both the elastic properties and breaking strain of SWCNT’s during tensile deformation. An analysis based on the virtual internal bond (VIB) model proposed by P. Zhang et al. is also presented for comparison. The results indicate that the proposed molecular mechanics approach is indeed an acceptable analytical method for analyzing the mechanical behavior of SWCNT’s. The project supported by the National Natural Science Foundation of China (10121202, 90305015 and 10328203), the Key Grant Project of Chinese Ministry of Education (0306) and the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU 7195/04E).     

Insights into the Allosteric Effect of SENP1 Q597A Mutation on the Hydrolytic Reaction of SUMO1 via an Integrated Computational Study

Small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a cysteine protease that catalyzes the cleavage of the C-terminus of SUMO1 for the processing of SUMO precursors and deSUMOylation of target proteins. SENP1 is considered to be a promising target for the treatment of hepatocellular carcinoma (HCC) and prostate cancer. SENP1 Gln597 is located at the unstructured loop connecting the helices α4 to α5. The Q597A mutation of SENP1 allosterically disrupts the hydrolytic reaction of SUMO1 through an unknown mechanism. Here, extensive multiple replicates of microsecond molecular dynamics (MD) simulations, coupled with principal component analysis, dynamic cross-correlation analysis, community network analysis, and binding free energy calculations, were performed to elucidate the detailed mechanism. Our MD simulations showed that the Q597A mutation induced marked dynamic conformational changes in SENP1, especially in the unstructured loop connecting the helices α4 to α5 which the mutation site occupies. Moreover, the Q597A mutation caused conformational changes to catalytic Cys603 and His533 at the active site, which might impair the catalytic activity of SENP1 in processing SUMO1. Moreover, binding free energy calculations revealed that the Q597A mutation had a minor effect on the binding affinity of SUMO1 to SENP1. Together, these results may broaden our understanding of the allosteric modulation of the SENP1−SUMO1 complex.     

Luminescence interference-free lifetime nanothermometry pinpoints in vivo temperature

Luminescence nanothermometry makes non-invasive and real-time temperature readings possible in living animals. However,the spectral fluctuation in tissues and fluids, as well as the interaction between fluorophores and environment hinders accuracy of the thermometry. Here, we report a luminescence lifetime-based nanothermometry which specifically addresses this problem. A temporal based calibration(lifetime sensing) in the NIR range, an endogenous thermal response as well as a polymer encapsulation evading environmental factors, altogether help to pinpoint temperature in vivo. Thanks to the highly condensed NdYb ions in a well-protected tiny core-shell nanocrystal(overall 11 nm), a temperature sensitivity about 2.07% K~(-1)(with 5% Yb~(3+) doped nanoparticles) and an accuracy of 0.27 K(with 25% Yb~(3+) doped nanoparticles) in biological fluids are achieved.Hopefully, combining thermally activated energy transfer nanothermometer with anti-interference lifetime thermometry would provide a more accurate temperature measurement for biological and preclinical studies.     

Domain Adaptation with Data Uncertainty Measure Based on Evidence Theory

Domain adaptation aims to learn a classifier for a target domain task by using related labeled data from the source domain. Because source domain data and target domain task may be mismatched, there is an uncertainty of source domain data with respect to the target domain task. Ignoring the uncertainty may lead to models with unreliable and suboptimal classification results for the target domain task. However, most previous works focus on reducing the gap in data distribution between the source and target domains. They do not consider the uncertainty of source domain data about the target domain task and cannot apply the uncertainty to learn an adaptive classifier. Aimed at this problem, we revisit the domain adaptation from source domain data uncertainty based on evidence theory and thereby devise an adaptive classifier with the uncertainty measure. Based on evidence theory, we first design an evidence net to estimate the uncertainty of source domain data about the target domain task. Second, we design a general loss function with the uncertainty measure for the adaptive classifier and extend the loss function to support vector machine. Finally, numerical experiments on simulation datasets and real-world applications are given to comprehensively demonstrate the effectiveness of the adaptive classifier with the uncertainty measure.     

新型含氮螯合树脂的制备及其吸附性能

以三甘醇和苯磺酰氯为原料,二乙烯三胺为交联剂合成了新型含氮螯合树脂(5),其结构经IR表征.讨论了Ni2 浓度和pH对5吸附容量的影响.动力学研究表明,5对Ni2 的吸附速率符合鲛岛公式.     

Nickel-catalyzed cross-electrophile allylation of vinyl bromides and the modification of anti-tumour natural medicine β-elemene

Herein, we present a facile and efficient allylation method via Ni-catalyzed cross-electrophile coupling of readily available allylic acetates with a variety of substituted alkenyl bromides using zinc as the terminal reductant. This Ni-catalyzed modular approach displays excellent functional group tolerance and a broad substrate scope, which the creation of a series of 1,4-dienes including several structurally complex natural products and pharmaceutical motifs. Moreover, the coupling strategy has the potential to realize enantiomeric control. The practicality of this transformation is demonstrated through the potent modification of the naturally antitumor active molecule β-elemene.

Herein, we present a facile and efficient allylation method via Ni-catalyzed cross-electrophile coupling of readily available allylic acetates with a variety of substituted alkenyl bromides using zinc as the terminal reductant.     

DMF体系中Cu2O球晶的制备及形貌分析

以N,N-二甲基甲酰胺(DMF)为溶剂,通过改变铜源和表面活性剂,调控反应参数,溶剂热条件下制备了三维十字形、空心及实心的Cu₂O球晶。利用XRD、SEM等表征手段,分析探讨了工艺条件变化对Cu₂O球晶形貌的影响。研究表明,随着DMF浓度的增大,体系的还原能力增强,Cu⁺增多,溶液的过饱和度增大,Cu₂O晶体集合体形态由晶体结构控制的各向异性与对称性的球晶逐渐向各向同性球晶演变。十二烷基硫酸钠(SDS)、十六烷基三甲基溴化铵(CTAB)、聚乙烯吡咯烷酮(PVP)等表面活性剂有助于降低溶液的过饱和度,增加结晶质的表面扩散能力,有利于规则形态Cu₂O晶粒的形成。反应体系中,Cu(Ac)₂·H₂O水解生成的羧基与DMF中的甲酰基在高温下发生脱羧反应产生CO₂气体以及SDS发泡作用产生的气体是形成空心Cu₂O球晶的重要原因。     

ZnO超细纳米线阵列的制备及其电化学性能

以Zn(NO₃)₂· 6H₂O和C₆H₁₂N₄为原材料,采用二步水热法在碳纤维布上合成了形貌尺寸均匀的ZnO超细纳米线阵列。用 X 射线衍射(XRD)和扫描电镜(SEM)对其晶体结构和形貌进行了表征,利用恒流充放电测试等手段对其进行电化学性能测试。测试结果表明,材料表现出优异的电化学性能。在200 mA/g的电流密度下循环150次后,ZnO超细纳米线阵列仍然约有730 mAh/g的充放电比容量,库伦效率保持在95%以上。在1 200 mA/g的大倍率条件下,材料的充放电比容量依旧可达481 mAh/g左右,表现出十分良好的循环稳定性和可逆性能,是一种较为理想的锂离子电池负极复合材料。