Cardiac autonomic nerve function and insulin sensitivity in obese subjects

OBJECTIVE: To investigate whether obesity influences cardiac autonomic nerve function. DESIGN: Comparing two groups of subjects with different degrees of obesity to normal weight controls. SUBJECTS: 19 healthy controls (mean age 33 y, BMI 21.7 +/- 0.2 kg/m2) and 17 obese non-diabetic subjects (mean age 39 y, BMI 33.7 +/- 1.8 kg/m2). MEASUREMENTS: Insulin sensitivity was calculated by an oral glucose tolerance test. Autonomic nerve function was evaluated by analysing the variation of the heart frequency at rest (coefficient variation of R-R intervals, REST 1), during deep respiration, at a Valsalva maneuver (longest/shortest R-R interval during inspiration hold) and by the Ewing test (ratio between the 30th and 15th R-R interval after reaching up-right position). RESULTS: The obese showed a lower insulin sensitivity than healthy controls (3.09 vs 4.60 mg x l2/mmol x mU x min, P < 0.001). Their variation in heart frequency was reduced (REST 1: 1.95 vs 2.9, P < 0.01, Valsalva: 1.30 vs 1.52 and Ewing test: 1.03 vs 1.14, P < 0.05). However, patients with moderate (BMI 31.7 kg/m2) or severe obesity (39.0 kg/m2) with identical insulin sensitivity had no significant difference in autonomic nerve function. Except for the Ewing test all measured parameters for the evaluation of cardiac autonomic nerve function correlated with the degree of diminished insulin sensitivity (REST 1: r = 0.475, P < 0.001). CONCLUSION: Moderate obesity with significantly decreased insulin sensitivity is associated with impaired cardiac autonomic nerve function.     

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.     

相容剂及其在PC/ABS合金中的应用

采用水相悬浮聚合法合成了SAN-g-MAH、SAN-g-MMA、SAN-g-GMA3种相容剂,比较了3种相容剂对PC/ABS合金的增容效果,着重研究了工艺条件对接枝率的影响及相容剂用量对合金力学性能的影响。结果表明,相容剂的最大接枝率可达5.76%,添加相容剂后,PC/ABS合金的力学性能有明显提高,拉伸强度和缺口冲击强度分别可达61.91MPa和10.12kJ/m2。     

Temporal course of perfusion in human masseter muscle during isometric contraction assessed by arterial spin labeling at 3T

Object  

Examination of blood perfusion in the masseter muscle in the course of repetitive isometric contraction by arterial spin-labeling (ASL) MR imaging and additional T2 relaxation time measurements during and after masseter muscle activation.     

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。