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.     

Novel Epoxides of Soloxolone Methyl: An Effect of the Formation of Oxirane Ring and Stereoisomerism on Cytotoxic Profile,Anti-Metastatic and Anti-Inflammatory Activities In Vitro and In Vivo

It is known that epoxide-bearing compounds display pronounced pharmacological activities, and the epoxidation of natural metabolites can be a promising strategy to improve their bioactivity. Here, we report the design, synthesis and evaluation of biological properties of αO-SM and βO-SM, novel epoxides of soloxolone methyl (SM), a cyanoenone-bearing derivative of 18βH-glycyrrhetinic acid. We demonstrated that the replacement of a double-bound within the cyanoenone pharmacophore group of SM with α- and β-epoxide moieties did not abrogate the high antitumor and anti-inflammatory potentials of the triterpenoid. It was found that novel SM epoxides induced the death of tumor cells at low micromolar concentrations (IC₅₀^(24h) = 0.7–4.1 µM) via the induction of mitochondrial-mediated apoptosis, reinforced intracellular accumulation of doxorubicin in B16 melanoma cells, probably by direct interaction with key drug efflux pumps (P-glycoprotein, MRP1, MXR1), and the suppressed pro-metastatic phenotype of B16 cells, effectively inhibiting their metastasis in a murine model. Moreover, αO-SM and βO-SM hampered macrophage functionality in vitro (motility, NO production) and significantly suppressed carrageenan-induced peritonitis in vivo. Furthermore, the effect of the stereoisomerism of SM epoxides on the mentioned bioactivities and toxic profiles of these compounds in vivo were evaluated. Considering the comparable antitumor and anti-inflammatory effects of SM epoxides with SM and reference drugs (dacarbazine, dexamethasone), αO-SM and βO-SM can be considered novel promising antitumor and anti-inflammatory drug candidates.     

渤海湾盆地渤南洼陷古近系沙河街组二段沉积相特征及演化

为了查明渤海湾盆地渤南洼陷沙河街组二段沉积相分布与演化规律,为油气勘探寻找接替区,在岩心、测井、录井及地震综合研究的基础上,对沙河街组二段进行了砂层组划分与对比,进而圈定了各个时期沉积相的展布范围并总结了沉积演化规律。研究结果表明：渤南洼陷沙二段可划分为4个砂层组,各砂组依次向南逐层超覆,沉积范围不断扩大。洼陷周缘凸起带附近主要发育扇三角洲前缘沉积,以水下分流河道微相为主;其次为河口砂坝与水下分流间湾。洼陷内部以滨浅湖滩坝为主,按其成因可分为正常砂质滩坝、砂岩-碳酸盐岩混积型滩坝以及风暴成因滩坝三类,不同类型砂坝分布规律各不相同。沙二段整体呈湖盆不断扩张、沉积范围不断扩大、扇三角洲分布减少而滩坝沉积规模不断扩大的沉积演化特征。     

Update on Glycosphingolipids Abundance in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Low numbers of HCC patients being suitable for liver resection or transplantation and multidrug resistance development during pharmacotherapy leads to high death rates for HCC patients. Understanding the molecular mechanisms of HCC etiology may contribute to the development of novel therapeutic strategies for prevention and treatment of HCC. UDP-glucose ceramide glycosyltransferase (UGCG), a key enzyme in glycosphingolipid metabolism, generates glucosylceramide (GlcCer), which is the precursor for all glycosphingolipids (GSLs). Since UGCG gene expression is altered in 0.8% of HCC tumors, GSLs may play a role in cellular processes in liver cancer cells. Here, we discuss the current literature about GSLs and their abundance in normal liver cells, Gaucher disease and HCC. Furthermore, we review the involvement of UGCG/GlcCer in multidrug resistance development, globosides as a potential prognostic marker for HCC, gangliosides as a potential liver cancer stem cell marker, and the role of sulfatides in tumor metastasis. Only a limited number of molecular mechanisms executed by GSLs in HCC are known, which we summarize here briefly. Overall, the role GSLs play in HCC progression and their ability to serve as biomarkers or prognostic indicators for HCC, requires further investigation.     

Biocompatibility and Mechanical Stability of Nanopatterned Titanium Films on Stainless Steel Vascular Stents

Nanoporous ceramic coatings such as titania are promoted to produce drug-free cardiovascular stents with a low risk of in-stent restenosis (ISR) because of their selectivity towards vascular cell proliferation. The brittle coatings applied on stents are prone to cracking because they are subjected to plastic deformation during implantation. This study aims to overcome this problem by using a unique process without refraining from biocompatibility. Accordingly, a titanium film with 1 µm thickness was deposited on 316 LVM stainless-steel sheets using magnetron sputtering. Then, the samples were anodized to produce nanoporous oxide. The nanoporous oxide was removed by ultrasonication, leaving an approximately 500 nm metallic titanium layer with a nanopatterned surface. XPS studies revealed the presence of a 5 nm-thick TiO₂ surface layer with a trace amount of fluorinated titanium on nanopatterned surfaces. Oxygen plasma treatment of the nanopatterned surface produced an additional 5 nm-thick fluoride-free oxide layer. The samples did not exhibit any cracking or spallation during plastic deformation. Cell viability studies showed that nanopatterned surfaces stimulate endothelial cell proliferation while reducing the proliferation of smooth muscle cells. Plasma treatment further accelerated the proliferation of endothelial cells. Activation of blood platelets did not occur on oxygen plasma-treated, fluoride-free nanopatterned surfaces. The presented surface treatment method can also be applied to other stent materials such as CoCr, nitinol, and orthopedic implants.     

Multisensor approach to determine changes of wetland characteristics in semiarid environments (central Spain)

Saline wetlands in the semiarid environment of Central Spain are fragile and highly dynamic ecosystems that are affected by degradation processes as a result of anthropological influences. An increase in agricultural production has led to the development of large-scale irrigation schemes with overexploitation of groundwater, and with consequent effects on the complex hydrology and associated land use. In this work, data from field, hyperspectral airborne, and multispectral satellite sensors are used in order to determine changes of wetland characteristics over time. The spectra of surface components (soil, vegetation, and salt crusts) were selected from the hyperspectral data and identified as endmembers using a site-specific spectral library. The spectral information contained in these endmembers was extrapolated to a temporal series of broadband multispectral imagery on which spectral unmixing analysis was performed in order to detect changes in the wetland over time. Results showed that the selected wetland components have undergone important changes in both their total area as well as their spatial distribution. These changes are mainly associated with the anthropogenic impact; however, natural influences due to seasonal fluctuations may coincide with the overall changes, although this in general is difficult to determine. Water regulation and agricultural practices directly influence the salinity of the soils and therefore the nature of the hygrophytic vegetation.     

The PANOPTIC Camera: A Plenoptic Sensor with Real-Time Omnidirectional Capability

A new biologically-inspired vision sensor made of one hundred “eyes” is presented, which is suitable for real-time acquisition and processing of 3-D image sequences. This device, named the Panoptic camera, consists of a layered arrangement of approximately 100 classical CMOS imagers, distributed over a hemisphere of 13 cm in diameter. The Panoptic camera is a polydioptric system where all imagers have their own vision of the world, each with a distinct focal point, which is a specific feature of the Panoptic system. This enables 3-D information recording such as omnidirectional stereoscopy or depth estimation, applying specific signal processing. The algorithms dictating the image reconstruction of an omnidirectional observer located at any point inside the hemisphere are presented. A hardware architecture which has the capability of handling these algorithms, and the flexibility to support additional image processing in real time, has been developed as a two-layer system based on FPGAs. The detail of the hardware architecture, its internal blocks, the mapping of the algorithms onto the latter elements, and the device calibration procedure are presented, along with imaging results.     

A Visible and Near-Infrared Light-Fueled Omnidirectional Twist-Bend Crawling Robot

In recent years, although light-driven soft actuators have attracted intense scientific attention and achieved remarkable progress, the design and construction of an intelligent robotic system with maneuverability, self-adaptability, untethered control, and greater freedom of action, in particular the omnidirectional motion capability on a plane, remains challenging. Herein, four types of photo-thermal fillers and an unprecedented twist-bend actuation mode is introduced into a liquid crystal elastomer-based soft robot. The obtained twist-bend crawling robot not only exhibits in situ rotation, four-way turning, and four-way linear motion under light irradiation with four wavelength bands (520, 655, 808, and 980 nm), but also demonstrates the ability to avoid obstacles in complex geographical environments. This work may bring a new perspective for fabrication and development of soft robots that can adapt to dynamic and complex environmental conditions.     

SiC devices for advanced power and high-temperature applications

Silicon carbide (SiC) process technology has made rapid progress, resulting in the realization of very promising electronic devices and sensors, enabling advanced solutions in power industry and mobile systems. In particular, for electronics working under harsh environmental conditions, SiC devices reach unprecedented performance. Transfer to production has already started for some applications     

A fully on-chip LDO voltage regulator with 37 dB PSRR at 1 MHz for remotely powered biomedical implants

This article presents a fully on-chip low-power LDO voltage regulator dedicated to remotely powered wireless cortical implants. This regulator is stable over the full range of alternating load current and provides fast load regulation achieved by applying a time-domain design methodology. Moreover, a new compensation technique is proposed and implemented to improve PSRR beyond the performance levels which can be obtained using the standard cascode compensation technique. Measurement results show that the regulator has a load regulation of 0.175 V/A, a line regulation of 0.024%, and a PSRR of 37 dB at 1 MHz power carrier frequency. The output of the regulator settles within 10-bit accuracy of the nominal voltage (1.8 V) within 1.6 μs, at full load transition. The total ground current including the bandgap reference circuit is 28 μA and the active chip area measures 290 μm × 360 μm in a 0.18 μm CMOS technology.