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.     

Nanoscale Insight Into Lead‐Free BNT‐BT‐xKNN

Piezoresponse force microscopy (PFM) is used to afford insight into the nanoscale electromechanical behavior of lead‐free piezoceramics. Materials based on Bi_1/2Na_1/2TiO₃ exhibit high strains mediated by a field‐induced phase transition. Using the band excitation technique the initial domain morphology, the poling behavior, the switching behavior, and the time‐dependent phase stability in the pseudo‐ternary system (1–x)(0.94Bi_1/2Na_1/2TiO₃‐0.06BaTiO₃)‐xK_0.5Na_0.5NbO₃ (0 <= x <= 18 mol%) are revealed. In the base material (x = 0 mol%), macroscopic domains and ferroelectric switching can be induced from the initial relaxor state with sufficiently high electric field, yielding large macroscopic remanent strain and polarization. The addition of KNN increases the threshold field required to induce long range order and decreases the stability thereof. For x = 3 mol% the field‐induced domains relax completely, which is also reflected in zero macroscopic remanence. Eventually, no long range order can be induced for x >= 3 mol%. This PFM study provides a novel perspective on the interplay between macroscopic and nanoscopic material properties in bulk lead‐free piezoceramics.     

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.     

Binary Controls on Interfacial Magnetism in Manganite Heterostructures

The complex interfacial correlations provide new routes toward tunable functionalities. Here, the wide range of tunabilities for magnetic properties are presented, including Curie temperature (from 245 to 320 K), coercive field (from 2 to 205 Oe), and saturated magnetic moment (from 0.9 to 2.8 µ_B Mn^?1), in a 9‐unit‐cell La_2/3Sr_1/3MnO₃ (LSMO) layer via modifying interfacial boundary conditions. Moreover, the LSMO/PbTiO₃‐based multilayers and superlattices that consist of PbTiO₃/LSMO/NdGaO₃ and PbTiO₃/LSMO/PbTiO₃ interfaces are characterized by two distinct Curie temperatures and coercive fields. The results reveal the feasibility of the interface‐resolved strategy based on boundary modification in fabricating potential devices with multiple accessible states for information storage. The wide‐range modulations on magnetic properties at LSMO/titanate interfaces are explained in terms of binary controls arising from the oxygen octahedral coupling (OOC) and magnetoelectric coupling (MEC). The results not only shed some light on understanding interfacial correlations in oxide heterostructures, but also pave an alternative path for exploring multiple accessible states in all‐oxide‐based electronic devices.     

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.     

Psychological services to Spanish-speaking populations: A model curriculum for training competent professionals.

The competent delivery of mental health services to Spanish-speaking clients requires knowledge of Latino cultures, racial and ethnic identity development, variables that impact service delivery, and the Spanish language. We present the Psychological Services for Spanish Speaking Populations (PSSSP) program as a model for training mental health professionals to deliver services to Spanish-speaking clients. The goals for the program were to improve participants' oral and written Spanish language proficiency in work-related contexts and to improve multicultural competence in service delivery to Latino clients. Recommendations for those who wish to offer similar programs include (a) grouping trainees according to Spanish language proficiency, (b) using Spanish language instructors with expertise in teaching heritage language learners, and (c) developing criterion references or measures to assess program outcomes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Water Concession Principles for Geothermal Aquifers in the Mura-Zala Basin,NE Slovenia

Demand for thermal water in the Mura-Zala basin, situated between Slovenia, Austria, Hungary and Croatia, is constantly increasing, with the sandy geothermal aquifer within the Neogene Mura formation being the most exploited. During the water concession granting process various problems were identified, together with the need for elaboration of the uniform concession granting principles. The latter were devised according to the specific hydrogeological settings and field inspection of 23 geothermal wells, performed through use of an adapted methodology. The inspection revealed changes in wells performance, low efficiency of energy abstraction and a lack of reinjection. The acquired information was applied to the development of particular principles, including the six key indicators. Firstly, a unified and integrated operational monitoring programme must be established, and upgraded by a national surveillance monitoring. Secondly, an application of the best available techniques is proposed. Stimulation of energetic and balneology efficiency is also needed, with recharge and reinjection conditions evaluated and applied where possible. Limited or full water concessions could be granted based on their fulfilment then. This continuous step-by-step approach should enable the implementation of adequate measures to meet the standards required for the thermal groundwater bodies according to the EU water framework directions.     

(Metal yolk)/(porous ceria shell) nanostructures for high-performance plasmonic photocatalysis under visible light

We describe a route to the preparation of (metal yolk)/(porous ceria shell) nanostructures through the heterogeneous growth of ceria on porous metal nanoparticles followed by the calcination-induced shrinkage of the nanoparticles. The approach allows for the control of the ceria shell thickness, the metal yolk composition and size, which is difficult to realize through common templating approaches. The yolk/shell nanostructures with monometallic Pt and bimetallic PtAg yolks featuring plasmon-induced broadband light absorption in the visible region are rationally designed and constructed. The superior photocatalytic activities of the obtained nanostructures are demonstrated by the selective oxidation of benzyl alcohol under visible light. The excellent activities are ascribed to the synergistic effects of the metal yolk and the ceria shell on the light absorption, electron-hole separation and efficient mass transfer. Our synthesis of the (metal yolk)/(porous ceria shell) nanostructures points out a way to the creation of sophisticated heteronanostructures for high-performance photocatalysis.