Secreted HSP90α-LRP1 Signaling Promotes Tumor Metastasis and Chemoresistance in Pancreatic Cancer

The extracellular heat shock protein 90α (eHSP90α) has been reported to promote cancer cell motility. However, whether pancreatic cancer (PC) cells expressed membrane-bound or secreted HSP90α, as well as its underlying mechanism for PC progression, were still unclear. Our study demonstrated that the amounts of secreted HSP90α proteins were discrepant in multiple PC cells. In addition, highly invasive Capan-2 cells have a higher level of secreted HSP90α compared with those of less invasive PL45 cells. The conditioned medium of Capan-2 cells or recombinant HSP90α treatment stimulated the migration and invasion of PC cells, which could be prevented with a neutralizing anti-HSP90α antibody. Furthermore, secreted HSP90α promoted elements of epithelial–mesenchymal transition in PL45 cells, including increases in vimentin and Snail expressions, decreases in E-cadherin expression, and changes in cell shape towards a mesenchymal phenotype, but these phenomena were reversed by the anti-HSP90α antibody in Capan-2 cells. In addition, high levels of low-density lipoprotein receptor-related protein 1 (LRP1) were associated with worsened patient survival in pancreatic adenocarcinoma. We demonstrated LRP1 as a receptor of eHSP90α for its stimulatory role in metastasis, by activating the AKT pathway. In addition, silencing LRP1 enhanced the chemosensitivity to gemcitabine and doxorubicin in Capan-2 cells. Therefore, our study indicated that blocking secreted HSP90α underlies an aspect of metastasis and chemoresistance in PC.     

Amyloid Formation in Nanoliter Droplets

Processes that monitor the nucleation of amyloids and characterize the formation of amyloid fibrils are vital to medicine and pharmacology. In this study, we observe the nucleation and formation of lysozyme amyloid fibrils using a facile microfluidic system to generate nanoliter droplets that can control the flow rate and movement of monomer-in-oil emulsion droplets in a T-junction microchannel. Using a fluorescence assay, we monitor the nucleation and growth process of amyloids based on the volume of droplets. Using the microfluidic system, we demonstrate that the lag phase, which is vital to amyloid nucleation and growth, is reduced at a lower droplet volume. Furthermore, we report a peculiar phenomenon of high amyloid formation at the edge of a bullet-shaped droplet, which is likely due to the high local monomer concentration. Moreover, we discovered that amyloid fibrils synthesized in the nanoliter droplets are shorter and thicker than fibrils synthesized from a bulk solution via the conventional heating method. Herein, a facile procedure to observe and characterize the nucleation and growth of amyloid fibrils using nanoliter droplets is presented, which is beneficial for investigating new features of amyloid fibril formation as an unconventional synthetic method for amyloid fibrils.     

A novel ethanol gas sensor based on ZnO-microwire

One-dimensional (1D) ZnO microwires were successfully synthesized by chemical vapor deposition and their structural and morphological properties were analyzed by X-ray diffraction and scanning electron microscopy, demonstrating that the microwires were single crystalline with perfect hexagonal structure and smooth surface. Using these 1D microstructures, we fabricated a novel ZnO-based ethanol gas sensor. Operating at room temperature, the sensor was found to have good sensing characteristics. The reliability and stability of the sensor could be improved by connecting multiple 1-wire devices (1-WD) in parallel into a multi-wires device. In interior natural lighting environment and under 3 V bias, the response and recovery time of the 1-WD to 200 ppm ethanol gas were <10 s and about 300 s, respectively, and the minimum and maximum detection limit were about 2 and 200 ppm, respectively. A sensing model was proposed for discussing the performance of the sensor. The simplicity in fabrication, low power consumption and low cost make the sensor suitable for practical application in many fields, especially in identifying driving under the influence and chemical industry monitoring.     

基于稀疏重建的信号DOA估计

从稀疏信号重建角度提出了一种改进的波达方向(DOA)估计方法。由于最小冗余线阵(MRLA)能以较少的阵元数获得较大的阵列孔径,将MRLA与l1-SVD方法相结合估计信号的DOA。仿真结果表明,经多次实验验证,所提方法是有效的,相比l1-SVD方法可以估计出更多信源的DOA,并且可以用较少的阵元数估计更多的信源DOA,具有信源过载能力。     

A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.     

Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

In patients with type 1 diabetes (T1D), compromised pancreatic β-cell functions are compensated through daily insulin injections or the transplantation of pancreatic tissue or islet cells. However, both approaches are associated with specific challenges. The transplantation of mesenchymal stem cells (MSCs) represents a potential alternative, as MSCs have tissue-forming capacity and can be isolated from various tissues. The human umbilical cord (hUC) is a good source of freely available MSCs, which can be collected through pain-free, non-invasive methods subject to minimal ethical concerns. We sought to develop a method for the in vitro generation of insulin-producing cells (IPCs) using MSCs. We examined the potential therapeutic uses and efficacy of IPCs generated from hUC-derived MSCs (hUC-IPCs) and human adipose tissue (hAD)-derived MSCs (hAD-IPCs) through in vitro experiments and streptozotocin (STZ)-induced C57BL/6 T1D mouse models. We discovered that compared to hAD-IPCs, hUC-IPCs exhibited a superior insulin secretion capacity. Therefore, hUC-IPCs were selected as candidates for T1D cell therapy in mice. Fasting glucose and intraperitoneal glucose tolerance test levels were lower in hUC-IPC-transplanted mice than in T1D control mice and hAD-IPC-transplanted mice. Our findings support the potential use of MSCs for the treatment of T1D.     

基于SQL Server数据库的安全性策略研究

从数据库系统的安全模型入手,讨论分析了SQL Server数据库使用中的安全问题,针对可能存在的安全问题,提出了一些具体的解决方法和建议,以提高用户对数据库安全的认识.     

用户初始服务密码管理方式

本文对用户初始服务密码管理困难的原因进行了深入的分析,提出了将初始服务密码印制在SIM卡涂层下的新型管理方式。