Enzyme-Activatable Polypeptide for Plasma Membrane Disruption and Antitumor Immunity Elicitation

Enzyme-instructed self-assembly of bioactive molecules into nanobundles inside cells is conceived to potentially disrupt plasma membrane and subcellular structure. Herein, an alkaline phosphatase (ALP)-activatable hybrid of ICG-CF₄KY^p is facilely synthesized by conjugating photosensitizer indocyanine green (ICG) with CF₄KY^p peptide via classical Michael addition reaction. ALP-induced dephosphorylation of ICG-CF₄KY^p enables its transformation from small-molecule precursor into rigid nanofibrils, and such fibrillation in situ causes severe mechanical disruption of cytomembrane. Besides, ICG-mediated photosensitization causes additional oxidative damage of plasma membrane by lipid peroxidation. Hollow MnO₂ nanospheres devote to deliver ICG-CF₄KY^p into tumorous tissue through tumor-specific acidity/glutathione-triggered degradation of MnO₂, which is monitored by fluorescent probing and magnetic resonance imaging. The burst release of damage-associated molecular patterns and other tumor antigens during therapy effectively triggers immunogenetic cell death and improves immune stimulatory, as demonstrated by the promotion of dendritic cell maturation and CD8⁺ lymphocyte infiltration, as well as constraint of regulatory T cell population. Taken together, such cytomembrane injury strategy based on peptide fibrillation in situ holds high clinical promise for lesion-specific elimination of primary, abscopal, and metastatic tumors, which may enlighten more bioinspired nanoplatforms for anticancer theranostics.     

增容作用对PET在PP中原位成纤及增强效果的影响

以接枝极性官能团的聚丙烯为增容剂,在保持一定拉伸比的条件下,与聚丙烯(PP)和聚对苯二甲酸乙二醇酯(PET)共混挤出。通过改变增容剂的用量,控制PET在PP中的形态结构。当增容剂含量为3%时,PET以纤维状分散在基体PP中,达到了较好的增强效果。     

Role of the ROS-JNK Signaling Pathway in Hypoxia-Induced Atrial Fibrotic Responses in HL-1 Cardiomyocytes

By promoting atrial structural remodeling, atrial hypoxia contributes to the development of the atrial fibrillation substrate. Our study aimed to investigate the modulatory effect of hypoxia on profibrotic activity in cultured HL-1 cardiomyocytes and explore the possible signaling transduction mechanisms of profibrotic activity in vitro. Hypoxia (1% O₂) significantly and time-dependently increased the expression of hypoxia-inducible factor (HIF)-1α and fibrotic marker proteins collagen I and III (COL1A and COL3A), transforming growth factor (TGF)-β1 and α-smooth muscle actin (SMA). Western blot or immunohistochemistry analysis showed that hypoxia-induced increase in COL1A and COL3A was significantly attenuated by the addition of SP600125 (a specific c-Jun N-terminal kinase [JNK] inhibitor) or expression of dominant-negative JNK before hypoxia treatment. The inhibition of hypoxia-activated phosphorylation of JNK signal components (JNK, MKK4, nuclear c-Jun and ATF-2) by pre-treatment with SP600125 could suppress hypoxia-stimulated HIF-1α upregulation and fibrotic marker proteins expression. Hypoxia significantly increased reactive oxygen species (ROS) production in cultured HL-1 atrial cells. Pre-treatment with N-acetylcysteine significantly abrogated the expression of nuclear HIF-1α, JNK transduction components and fibrotic marker proteins. Taken together, these findings indicated that the hypoxia-induced atrial profibrotic response occurs mainly via the ROS/JNK pathway, its downstream upregulation of HIF-1α and c-Jun/ATF2 phosphorylation and nuclear translocation to up-regulate the expression of fibrosis-related proteins (COL1A, COL3A, TGF-β1 and α-SMA). Our result suggests that suppression of ROS/JNK signaling pathway is a critical mechanism for developing a novel therapeutic strategy against atrial fibrillation.     

基于复杂网络映射的房颤脉检测

为了探索脉搏波中蕴含的复杂性及简便快速地检测心房颤动,结合中国传统医学中“房颤脉”的概念,设计了一种基于复杂网络的房颤脉检测方法。将光电容积脉搏波的时间序列按可视图法映射成复杂网络,将平均心率与复杂网络的度分布作为支持向量机的输入,基于高斯径向核函数设计了二分类的支持向量机。针对阵发性房颤患者的实验表明,这种方法可以有效地分辨病人的发病状态和正常状态。     

Modeling of high-affinity binding of the novel atrial anti-arrhythmic agent, vernakalant, to Kv1.5 channels

Vernakalant (RSD1235) is an investigational drug that converts atrial fibrillation rapidly and safely in patients intravenously [Roy et al., J. Am. Coll. Cardiol. 44 (2004) 2355–2361; Roy et al., Circulation 117 (2008) 1518–1525] and maintains sinus rhythm when given orally [Savelieva et al., Europace 10 (2008) 647–665]. Here, modeling using AutoDock4 allowed exploration of potential binding modes of vernakalant to the open-state of the Kv1.5 channel structure. Point mutations were made in the channel model based on earlier patch-clamp studies [Eldstrom et al., Mol. Pharmacol. 72 (2007) 1522–1534] and the docking simulations re-run to evaluate the ability of the docking software to predict changes in drug–channel interactions. Each AutoDock run predicted a binding conformation with an associated value for free energy of binding (FEB) in kcal/mol and an estimated inhibitory concentration (K_i). The most favored conformation had a FEB of −7.12 kcal/mol and a predicted K_i of 6.08 μM (the IC50 for vernakalant is 13.8 μM; [Eldstrom et al., Mol. Pharmacol. 72 (2007) 1522–1534]). This conformation makes contact with all four T480 residues and appears to be clearly positioned to block the channel pore.     

Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates

Nanoparticles are useful for increasing drug stability, solubility, and availability. The small molecule baicalein inhibits fibrillation, and detoxifies aggregates of α-synuclein (αSN) associated with Parkinson's disease (PD), but it suffers from instability, low solubility and consequent low availability. Here it is demonstrated that incorporation of baicalein into zwitterionic nanoliposomes (NLP-Ba) addresses these problems. NLP-Ba inhibits αSN fibril initiation, elongation, secondary nucleation, and also depolymerizes mature fibrils more effectively than free baicalein and prevents soluble αSN aggregates from seeding new fibrils. Importantly, NLP-Ba perturbs oligomers’ capacity to permeabilize the membrane. The interaction between NLP-Ba and αSN is confirmed by different biophysical techniques. This nanosystem crosses the blood-brain barrier in vitro and is effective against rotenone neurotoxicity in vivo. The effect of NLP-Ba on αSN fibrillation/cytotoxicity is attributed to a combination of free baicalein and empty NLPs. The results indicate a neuroprotective role for NLP-Ba in decreasing αSN pathogenicity in PD and highlight the use of nanoliposomes to mobilize poorly soluble hydrophobic drugs.     

ECG Classification Using Deep CNN Improved by Wavelet Transform

Atrial fibrillation is the most common persistent form of arrhythmia. A method based on wavelet transform combined with deep convolutional neural network is applied for automatic classification of electrocardiograms. Since the ECG signal is easily inferred, the ECG signal is decomposed into 9 kinds of subsignals with different frequency scales by wavelet function, and then wavelet reconstruction is carried out after segmented filtering to eliminate the influence of noise. A 24-layer convolution neural network is used to extract the hierarchical features by convolution kernels of different sizes, and finally the softmax classifier is used to classify them. This paper applies this method of the ECG data set provided by the 2017 PhysioNet/CINC challenge. After cross validation, this method can obtain 87.1% accuracy and the F1 score is 86.46%. Compared with the existing classification method, our proposed algorithm has higher accuracy and generalization ability for ECG signal data classification.     

Human Serum Transferrin Fibrils: Nanomineralisation in Bacteria and Destruction of Red Blood Cells

Fibrils formed by human serum transferrin [(1–3 μM ) apo‐Tf, partially iron‐saturated (Fe_0.6‐Tf) and holo‐Tf (Fe₂‐Tf) forms], from dilute bicarbonate solutions, were deposited on formvar surfaces and studied by electron microscopy. We observed that possible bacterial contamination appears to give rise to long, pea‐pod‐like (PPL) structures for Fe₂‐Tf, attributable to the formation of polyhydroxybutyrate (PHB) storage granules, under the nutrient‐limiting conditions used. These PPL structures contained periodic nanomineralisation sites susceptible to uranyl stain. Extended incubation of transferrin solutions (about four days) gave rise to extensive transferrin fibril structures. Optical microscopy and AFM studies showed that red blood cells (RBCs) readily adhere to these fibrils. Moreover, the fibrils appear to penetrate RBC membranes and to induce rapid cell destruction (within about 5 h). It is speculated that in situations in vivo where transferrin fibrils can form, such interactions might have adverse physiological consequences, and further studies could aid the understanding of related pathological events.     

Tencel/棉混纺机织物前处理工艺的研究

Tencel纤维为一种再生纤维素纤维,其染整前处理加工特性与传统的纤维素纤维有所不同.本文讨论了Tencel/棉混纺机织物前处理加工工艺,并对加工设备、助剂和加工条件选择进行了进一步的研究.提出了适合Tencel/棉混纺织物的前处理工艺.     

Effects of alkali pretreatment on lyocell woven fabric and its influence on pilling properties

Abstract

Experiments were conducted to study the influence of various concentration of alkalis on the pilling properties of lyocell fabrics. Generally, the lyocell fabric has more tendency of pill formation due to fibrillation properties. Therefore, present work is focused on the impact of alkali pretreatments with various concentration from 0.5?mol/L to 3?mol/L on lyocell with their pilling resistance. Due to the morphological changes, pilling results are attributed to the alkali types and their concentration. Treatment with TmAH and LiOH at 2?mol/L shows the reduction of a number of fibrils leading to reduce the pill generation significantly. Carboxyl content and iodine sorption value are analyzed to find the impact of alkali on the accessible region and structural changes respectively, also surface modification was observed by SEM to confirm the surface characteristics. Overall results shows that the reduction of fibrillation leads to better pilling resistance of lyocell fabric.