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Objective. Acute lung injury (ALI) is one of the common and severe complications of cardiopulmonary bypass (CPB), which is the primary cause of death in intensive care units. Nevertheless, there is a lack of effective treatment for ALI secondary to CPB. κ-Opioid receptor (KOR) agonists have been demonstrated to improve lung function after pulmonary hypertension. However, its protective role has been barely reported in CPB-induced acute respiratory distress syndrome (ARDS). Therefore, this research focused on the protective effect of a KOR agonist U50448H on ARDS and investigated its potential relationship with the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Method. Forty-five rats were randomly allocated into Sham, CPB, and U50448 groups (n = 15 rats/group). After a CPB model was successfully established in rats, CPB rats were treated with the KOR agonist U50448H. The values of extravascular lung water (EVLW), alveolar-arterial oxygen tension difference (AaDO2), and respiratory index (RI) were examined, and the lung wet/dry (W/D) weight ratio was also calculated. Western blot (WB) was utilized to measure the expression of MMP-9, GSDMD-C, GSDMD-N, NLRP3, ASC, pro-Caspase-1, pro-IL-1β, and α7-nAChR. The immunofluorescence assay was performed for examining the expression of ROS, F480, iNOS, CD206, and α7-nAChR. Cell apoptosis was detected by the TUNEL assay. ELISA was used to test the level of LPS in serum and the level of MDA, GSH, SOD, TNF-α, IL-4, IL-6, IL-18, and IL-1β in lung tissues. Results. It was observed that the administration of U50448H significantly reduced EVLW values and LPS levels in the lung of rats. Meanwhile, U50448H increased AaDO2 values while decreasing RI values. Moreover, the administration of U50448H alleviated the pathological damage caused by ALI secondary to CPB. U50448H repressed ROS release and oxidative stress responses, as well as lowered LPS levels in plasma and MMP-9 expression in the lung of CPB rats. Furthermore, U50448H facilitated the shift of macrophage phenotype to M2. In addition, U50448H decreased the activity of the CAP-NLRP3 inflammasome and suppressed pyroptosis in pulmonary cells. Conclusion. The KOR agonist U50448H improved lung function and relieved lung injury in CPB rats, accompanied by diminished ROS and MMP-9 levels in lung tissues, promoted macrophage polarization from M1 to M2, and reduced NLRP3 inflammasome activities. These results indicated U50448H as a promising drug for the treatment of ALI secondary to CPB.

Hearing loss is one of the most common chronic developmental diseases.The available studies have demonstrated that the occurrence and development of hearing loss is closely related to oxidative damage caused by oxidative stress.Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase,NOX) contribute to the production of reactive oxygen and are classified into seven subtypes (NOX1,NOX2,NOX3,NOX4,NOX5,DUOX1,and DUOX2).To explore the relationship between oxidative stress and hearing loss,this paper reviews the latest research progress in the pathological mechanism of NOX-mediated oxidative stress and hearing loss.

To compare the femoral and tibial tunnel positions of anterior cruciate ligament reconstruction using the modified transtibial (MTT) technique and anteromedial (AM) portal technique.Between January 2017 and September 2020, 78 patients with anterior cruciate ligament rupture underwent single-bundle reconstruction with the modified transtibial technique in 39 cases (group MTT) and through anteromedial approach in 39 cases (group AM). There were 25 males and 14 females in group MTT, with an average age of (37.0±2.3) years old; 27 males and 12 females in group AM, with an average age of (37.5±2.2) years old. CT scan of the affected knee was conducted one week after the surgery to measure and compare the femoral tunnels positioning (Fx, Fy), tibial tunnels positioning in the frontal plane(Tx1), tibial tunnels positioning in the sagittal plane (Ty1), and tibial tunnels positioning in the axial plane (Tx2, Ty2) in patients undergoing anterior cruciate ligament reconstruction through Mimics software.Three-dimensional CT reconstruction after the surgery showed that the average Fx and Fy were(25.2±2.1)% and (34.9±3.0)% respectively and the Tx1 and Ty1 were (45.5±3.3)% and (44.7± 3.0)% respectively, while the Tx2 and Ty2 were (47.0±3.0)% and (39.9±4.2)% respectively in group MTT. In group AM, the average Fx and Fy were (26.0±2.0)% and (36.1±3.9)% respectively and the Tx1 and Ty1 were (46.5±3.1)% and (45.6± 3.1)% respectively, while the Tx2 and Ty2 were (47.4±2.5)% and (39.6±3.9)% respectively. There were no statistically significant differences in the femoral and tibial tunnels between the two groups (Both the MTT and AM technique can achieve good anatomical positioning of the femoral and tibial tunnels, without significant differences in the positioning of the bone tunnels.

Background/Aims: Renal ischemia-reperfusion injury (IRI) is a common consequence of acute kidney injury. Nicotinamide adenine dinucleotide phosphate (NADPH), which is derived from the pentose phosphate pathway, is essential for the proper functioning of essential redox and antioxidant defense systems. Previous studies have indicated that NADPH is responsible for protecting the brain from ischemic injury. The goal of this study was to analyze the protective function of NADPH in renal IRI. Methods: The IRI animal model was generated through a midline laparotomy surgery that clamped both sides of the renal pedicles for 40 min to induce renal ischemia. The in vitro model was generated by removing oxygen and glucose from human kidney epithelial cells (HK-2 cells), followed by reoxygenation to imitate IRI. Renal function and histopathological changes were observed and evaluated. Additionally, malondialdehyde and glutathione levels were determined in renal tissue homogenate as indicators of oxidative stress. ROS production in cells was determined by DHE staining. Protein biomarker expression was evaluated by western blot, apoptosis was analyzed by TUNEL staining, and p65 nuclear translocation was visualized by immunofluorescence. Results: Our data indicated that NADPH safeguarded the kidneys from histological and functional damage, and significantly reduce cell injury along with preventing potential increases in blood urea nitrogen and creatinine levels. Furthermore, we observed that NADPH increased glutathione levels, while reducing levels of malondialdehyde and reactive oxygen species. Additionally, our results suggested that NADPH treatment may alleviate IRI-induced apoptosis and inflammation. Conclusion: NADPH treatment may protect against renal IRI and should be further developed as a new treatment for acute kidney injury.

We performed this meta-analysis to analyze the cancer risk to individuals carrying the rs701848 and rs2735343 single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) gene. We searched the PubMed, EMBASE, Cochrane library and the national knowledge infrastructure of China (CNKI) databases and identified 18 eligible case-control studies with 5458 cases and 6003 controls for rs701848 as well as 5490 cases and 6209 controls for rs2735343. Our analyses demonstrated that cancer risk was associated with rs701848 in the recessive model (CC vs. CT+TT, OR=1.169, 95% CI: 1.061-1.288) and with rs2735343 in the dominant model (GC+CC vs. GG, OR=0.758, 95% CI: 0.590-0.972). Subgroup analysis showed that in Asian subjects, carrying the C allele of rs701848 or GG genotype of rs2735343 was associated with increased cancer risk. Moreover, Asian subjects carrying the TC/CC genotype or C allele of rs701848 were associated with increased risk of esophageal squamous cell cancer. This meta-analysis indicates that the PTEN rs701848 (CC) and rs2735343 (GG) polymorphisms are associated with increased cancer risk in Asian subjects.

Trichoid sensilla are the most common mechanoreceptors in insects; depending on their distribution, they can act as either exteroceptors or proprioceptors. In this study, the internal structure of the trichoid sensillum from Nilaparvata lugens was studied, using focused ion beam scanning electron microscopy (FIB-SEM). We reconstructed a three-dimensional (3D) model derived from the FIB-SEM data set. The model displayed characteristic mechanosensory sensilla components, including a hair inserted in the socket, a dendrite going through the laminated cuticle, and an electron-dense tubular body at the dendrite terminal. The detailed 3D model showed the relationship between the microtubules within the tubular body and those outside of the tubular body. We also found an autocellular junction in the tormogen cell, indicating that the tormogen cell grows around the dendrite sheath to form a hollow column shape during sensilla morphogenesis.

Compared with conventional two-dimensional transmission electron microscopy (TEM), focused ion beam scanning electron microscopy (FIB-SEM) can provide more comprehensive 3D information on cell substructures at the nanometer scale. Biological samples prepared by cryofixation using high-pressure freezing demonstrate optimal preservation of the morphology of cellular structures, as these are arrested instantly in their near-native states. However, samples from cryofixation often show a weak back-scatter electron signal and bad image contrast in FIB-SEM imaging. In addition, it is impossible to do large amounts of heavy metal staining. This is commonly achieved via established osmium impregnation (OTO) en bloc staining protocols. Here, we compared the FIB-SEM image quality of brain tissues prepared using several common freeze-substitution media, and we developed an approach that overcomes these limitations through a combination of osmium tetroxide, uranyl acetate, tannic acid, and potassium permanganate at proper concentrations, respectively. Using this optimized sample preparation protocol for high-pressure freezing and freeze-substitution, perfect smooth membrane morphology, even of the lipid bilayers of the cell membrane, was readily obtained using FIB-SEM. In addition, our protocol is broadly applicable and we demonstrated successful application to brain tissues, plant tissues, Caenorhabditis elegans, Candida albicans, and chlorella. This approach combines the potential of cryofixation for 3D large volume analysis of subcellular structures with the high-resolution capabilities of FIB-SEM.

A control method is proposed to improve vehicle yaw stability based on neural network predictive. A vehicle steering model using neural network control strategy is set up, at the same time, the nonlinear predictive functional control using the neural network model is developed for control of high-nonlinear system. New structure of neural network multi-step prediction that is different from cascade or parallel is given. The results illustrate that the nonlinear predictive functional control using neural network model is more effective for control nonlinear system than PID control. A simulation is performed with it during two different conditions: step input and sinusoidal input, the results showed that compared with uncontrolled, the presented controller achieve good steady response of side slip angle and yaw rate, and lighten the burden of the driver and improve vehicle yaw stability.

Sphingosine kinase functions to phosphorylate sphingosine to sphingosine 1-phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Although SphK1 and SphK2 share high sequence similarity, SphK2 has distinct distribution, regulation and function. SphK2 is involved in the pathological processes of varieties of diseases including cancer, neurodegenerative disorders, stroke, cardiovascular diseases and inflammation. SphK2 may promote the proliferation of cancer cells and the progression of inflammation. The SphK2/S1P pathway is also involved in the pathogenesis of neurodegenerative disorders and stroke. S1P produced by SphK2 in the nucleus binds to HDACs, which then inhibits histone acetylation and regulates memory. The SphK2 pathway mediates platelet aggregation, thrombosis, cardioprotection and helps to ameliorate hepatic steatosis. This review focuses on the recent advances in research on SphK2 regulation and its potential roles in diseases, highlighting SphK2 may be a novel therapeutic strategy for diseases.

Terminal erythroid differentiation and its regulation occurs in the bone marrow specialized structure termed erythroblastic islands. The role of macrophages in erythropoiesis is closely related with the integrity of erythroblastic island, which is reliant on adhesive interactions between erythroid and macrophage cells. In regulating red blood cell homeostasis of adult, macrophages have 2 major roles, retaining erythroblast in bone marrow, controlling the final maturation of erythroblasts into reticulocytes and clearing old erythrocytes. Recent research demonstrated that body can affect erythropoiesis by regulating the function of macrophages in physiological or pathological conditions. This paper review focuses on the new advances of this aspect in recent years, including adhesion factor and regulatory factor between macrophage and red blood cells, role of macrophage in development of red blood cells, effect of macrophage on erythropoiesis in different conditiones and so on.

Our previous findings suggest that sphingosine kinase 2 (SPK2) mediates ischemic tolerance and autophagy in cerebral preconditioning. The aim of this study was to determine by which mechanism SPK2 activates autophagy in neural cells. In both primary murine cortical neurons and HT22 hippocampal neuronal cells, overexpression of SPK2 increased LC3II and enhanced the autophagy flux. SPK2 overexpression protected cortical neurons against oxygen glucose deprivation (OGD) injury, as evidenced by improvement of neuronal morphology, increased cell viability and reduced lactate dehydrogenase release. The inhibition of autophagy effectively suppressed the neuroprotective effect of SPK2. SPK2 overexpression reduced the co-immunoprecipitation of Beclin-1 and Bcl-2, while Beclin-1 knockdown inhibited SPK2-induced autophagy. Both co-immunoprecipitation and GST pull-down analysis suggest that SPK2 directly interacts with Bcl-2. SPK2 might interact to Bcl-2 in the cytoplasm. Notably, an SPK2 mutant with L219A substitution in its putative BH3 domain was not able to activate autophagy. A Tat peptide fused to an 18-amino acid peptide encompassing the native, but not the L219A mutated BH3 domain of SPK2 activated autophagy in neural cells. The Tat-SPK2 peptide also protected neurons against OGD injury through autophagy activation. These results suggest that SPK2 interacts with Bcl-2 via its BH3 domain, thereby dissociating it from Beclin-1 and activating autophagy. The observation that Tat-SPK2 peptide designed from the BH3 domain of SPK2 activates autophagy and protects neural cells against OGD injury suggest that this structure may provide the basis for a novel class of therapeutic agents against ischemic stroke.

MicroRNAs play important roles in tumorigenesis of various types of cancers. MiR-320a can inhibits cell proliferation of some cancers, but the biologic roles of miR-320a in lung cancer need to be further studied. Here, we investigated the roles of miR-320a in suppressing the proliferation of lung adenocarcinoma cells. MiR-320a treatment was found to effectively suppress LTEP-a-2 and A549 cell proliferation, and induce more apoptotic cells with irradiation treatment compared with control treatment. Our results also showed that miR-320a, as a novel miRNA, directly regulated signal transducer and activator of transcription 3 (STAT3) and its signals, such as Bcl-2, Bax, and Caspase 3. The siRNA-inhibited STAT3 levels further proved its roles in regulating STAT3 signals. Moreover, miR-320a treatment effectively suppressed cancer cell growth in mice xenografts compared with controls, and significantly inhibited cell migration in vitro and in vivo. Our findings collectively demonstrated that miR-320a, by directly regulating STAT3 signals, not only suppressed cell proliferation and metastasis, but also enhanced irradiation-induced apoptosis of adenocarcinomia cells.

With the railway freight organization reform, the development of China railway to the modern logistics industry becomes an inevitable trend. Nowadays, there is an existing railway freight information system, but the content is limited to the traditional transportation industry. Therefore, applying IoT to establish a modern railway logistics system platform should be considered. In the long run, the system platform will greatly benefit to the development of China railway industry.

Twenty-four kinds of coking coals which have different ranks are selected to investigate the sulfur transformation during coking process. The form sulfur in coals and cokes are determined by wet chemical method. The results show that the conversion of total sulfur during coal coking process is influenced by volatile content of coal and the content of the inertinite. The conversion of total sulfur is high for the large volatile content in coal. There is some linear correlation between the average conversion of total sulfur and the average inertinite content, this paper presents that the average conversion of total sulfur is high for the low average inertinite content. We also foud that coke sulfur depends primarily on the amount of coal sulfur, and the transformed capability of sulfide sulfur is stronger than that of the organic sulfur conversion for coal during coking process.

Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH) and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis.

Vehicle under braking in turn condition can easily cause lateral instability because of the centrifugal force. In this paper, the defects of ABS control methods of the vehicle under braking in turn condition were analyzed, a braking force control strategy by the integrated control of ABS and yaw moment control for vehicle cornering is presented. Based on ABS, a yaw moment controller using fuzzy control theory is designed, by controlling yaw moment of vehicle and regulating slip rate of wheels, the dynamic regulation of yaw moment in vehicle braking is realized, therefore, vehicle braking stability on turning lane is improved. A simulation is performed with it during two different conditions: step input and sinusoidal input, the results showed that the transient and steady response based on presented method is better than that of ABS only, and the presented method can effectively control the yaw rate and side slip angle synchronously, achieve good transient and steady response, lighten the burden of the driver and improve vehicle yaw stability.

While PSS is fundamental for the development of solution oriented partnerships, the stakeholders’ distribution of profit is not defined an operational paradigm yet. In this article, we provide a brief overview of the diesel engine in the area of Product Service Systems. Firstly, we establish the model of Diesel Engine PSS, when we analysis the product features of diesel engine and the features of PSS for diesel engine. The application of PSS in diesel engine area may be different from other manufacturing, but the intrinsic complexity of PSS, which include Convenient, science and the economy, can be proved for the stakeholders. So then we summarize the stakeholders of PSS, and understand the relationship of stakeholders’ profit structure. Finally, we design the profit model of diesel engine PSS. The main content is that how to get the quantization of the stakeholders’ profit and the balance the profit model of diesel engine PSS which can decide to the trade of diesel engine products-services smoothly.

Glutathione S-transferase P1-1 (GSTP1-1, EC 2.5.1.18) is generally conceived to be an important player in the acquired resistance of tumor to anticancer agents, thus a series of quinolinoneacetic acid derivatives were synthesized and their inhibitory effects on GSTP-1 were tested in this study. Interestingly, it was found that some compounds showed remarkable inhibitory effect on GSTP-1 activity. Furthermore, molecular docking study was conducted to provide the binding modes of quinolinoneacetic acid derivatives on GSTP1-1 activity. In summary, we present the discovery of a series of quinolinoneacetic acid compounds as inhibitors of GSTP1-1 and their interaction modes toward GSTP1-1 binding site.

In the present study, classification and regression trees (CART) was employed for quantitative structure–activity relationships (QSAR) studies of heterogeneous sets of antimicrobial agents against Candida albicans , compared with multiple linear regression (MLR). More than hundred descriptors calculated by Material Studio 4.0 software system were used as the original variables for CART modeling. As to MLR modeling, the splitting variables in CART were taken as the original inputs. Experimental results revealed that the well correlation between the structurally heterogeneous series of antimicrobial agents and the antimicrobial potencies against C. albicans was obtained by CART. In addition, descriptors S_ssO, octupole-yyz, heat of formation, Balaban index-JX, octupole-xzz, shadow_Ly, dipole-z, molecular flexibility, shadow_YZ, Zagreb index, quadrupole-yz and density were found to play the most predominant roles in the antimicrobial activities against C. albicans .

Physico-chemical and flocculating properties of a bioflocculant, producing by a Serratia plumuthica isolate, were studied. The bioflocculant was identified as an acid polysaccharide consisting of galactose, talose, glucose, mannose and galaturonic acid in a ratio of 34.5:5.1:24.5:29.6: 9.2. Its molecular weight was estimated to be 1.8×106. The bioflocculant was found to be effective for flocculation of a kaolin suspension, when added at a concentration of 1~10 mg/L, in a broad pH range of 2~9 and temperature range of 10~80°C. Its flocculating activity was synergistically stimulated by the bivalent or trivalent cations such as Ca2+, Mg2+, Al3+ and Fe3+. In addition, it could efficiently flocculate a variety of suspensions, including paper-making wastewater, oil-producing wastewater, black ink, alga cell suspension and activated sludge.

Resistance to chemotherapeutic drugs has long been a considerable barrier to successful treatment of many cancers and over-expression of glutathione S-transferase P1-1 is correlated to carcinogenesis and resistance of cancer cells against chemotherapeutic agents. This study throws light on the role of chalcone derivatives, a new class of glutathione S-transferase P1-1 inhibitors potentially to overcome glutathione S-transferase P1-1-mediated chemotherapy resistance. Nineteen alpha-substituted chalcone derivatives were synthesized and their in vitro inhibitory effects on glutathione S-transferase P1-1 were determined. We interestingly found that most of these compounds showed inhibitory effect on glutathione S-transferase P1-1 activity. In addition, molecular field-based similarity analysis provides the necessary three-dimensional molecular field properties of alpha, beta-unsaturated carbonyl derivatives to inhibit glutathione S-transferase P1-1 activity. Thus, these compounds have great potential to be developed into novel chemotherapeutic sensitizers.

The configuration of classification and regression trees (CART) used to include tree-growing by greedy recursive partitioning, which selects the splitting parameters (i.e., splitting variables and values) involved in tree, and tree-pruning, which aims to obtain a final tree of right size. This method is successful for most applications; however, it presents some well-known limitations and drawbacks, such as, less comprehensibility, inclination to overfitting, and suboptima. In the present study, the modified discrete particle swarm optimization method was invoked to adaptively configure the globally optimal CART (MPSOCART) via simultaneously selecting the optimal splitting parameters in CART and the appropriate structure of CART. A new objective function was formulated to decide the appropriate CART architecture and the optimum splitting parameters. The proposed MPSOCART was applied to predict the bioactivities of flavonoid derivatives and inhibitory activities of inhibitors of epidermal growth factor receptor tyrosine kinase, compared with partial least-squares and CART induced by greedy recursive partitioning. The comparison revealed that MPSO was a useful tool for inducing a globally optimal CART, which converges fast to the optimal solution and avoid overfitting in great extent.

Two kinds of organic light-emitting device were prepared with the same structure of ITO/PVK:Ir(ppy)3(100:2)/BCP(10 nm)/Alq3(20 nm)/Al, but with different evaporation conditions for the hole-blocking layer BCP and the charge-transporting layer Alq3. The films of BCP and Alq3 in device 1 were prepared with the chamber in complete darkness, and in device 2 they were prepared with light irradiation from a 100 W filament lamp during the thermal evaporation process. The current density and light power versus voltage in the two devices are reported. The results show that the current density and light power of device 2 were respectively 2.5 times and 4 times respectively as high as that of device 1 under the same driving voltage 20 V.

Background Our previous finding showed that brain ischemic preconditioning mediates neuroprotection through endoplasmic reticulum (ER) stress-induced autophagy. This study was aimed at exploring the role of ER chaperone GRP78 in IPC induced autophagy activation in neural cells. Results Ischemic preconditioning (IPC) and oxygen glucose deprivation (OGD) models were established in rat pheochromocytoma (PC12) cells and primary cultured murine cortical neurons. IPC exerted neuroprotection against subsequent OGD injury in both PC12 cells and primary cortical neurons. IPC increased GRP78 expression and activated autophagy, as evidenced by upregulated LC3 and Beclin1, increased autophagic flux and formation of autophagosomes. BAPTA(dibromo-1,2-bis(aminophenoxy)ethane N,N,N9,N9 - tetra acetic acid, 0.125-2 μM) and small interfering RNA targeted GRP78 abrogated IPC induced neuroprotection and decreased the expression of GRP78, LC3II/LC3I and Beclin1. In contrast, lentiviral vector mediated GRP78 overexpression (LV-GRP78) strengthened resistance of PC12 cells to OGD injury and increased LC3 and Beclin1 expression. Moreover, knockdown of GRP78 in stable GRP78 overexpressing PC12 cells abolished the upregulation of LC3II/LC3I. GRP78 might activate autophagy through AMPK - mTOR pathway. Conclusion These results suggest that IPC- induced GRP78 upregulation is involved in autophagy activation, and hence exerts protection against ischemic injury in neural cells. Electronic supplementary material The online version of this article (doi:10.1186/s13041-015-0112-3) contains supplementary material, which is available to authorized users.

Visceral hypersensitivity represents an important hallmark in the pathophysiology of irritable bowel syndrome (IBS), of which the mechanisms remain elusive. The present study was designed to examine whether cation-chloride cotransporter (CCC)-mediated chloride (Cl−) homeostasis of the spinal cord is involved in chronic stress-induced visceral hypersensitivity. Chronic visceral hypersensitivity was induced by exposing male Wistar rats to water avoidance stress (WAS). RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of CCCs in the spinal cord. Patch-clamp recordings were performed on adult spinal cord slices to evaluate Cl−homeostasis and Cl−extrusion capacity of lamina I neurons. Visceral sensitivity was estimated by measuring the abdominal withdrawal reflex in response to colorectal distension (CRD). After 10 days of WAS exposure, levels of both total protein and the oligomeric form of the K+-Cl−cotransporter isoform 2 (KCC2), but not Na+-K+-2Cl−transporter isoform 1 (NKCC1), were significantly decreased in the dorsal horn of the lumbosacral spinal cord. The downregulation of KCC2 resulted in a depolarizing shifted equilibrium potential of GABAergic inhibitory postsynaptic current and impaired Cl−extrusion capacity in lamina I neurons of the lumbosacral spinal cord from WAS rats. Acute noxious CRD disrupted spinal KCC2 expression and function 2 h after the final distention in sham rats, but not in WAS rats. Pharmacological blockade of KCC2 activity by intrathecal injection of a KCC2 inhibitor [(dihydroindenyl)oxy] alkanoic acid enhanced visceral nociceptive sensitivity in sham rats, but not in WAS rats. These results suggest that KCC2 downregulation-mediated impairment of spinal cord Cl−homeostasis may play an important role in chronic stress-induced visceral hypersensitivity.

Communication between neurons and glia in the dorsal root ganglia (DRG) and the central nervous system is critical for nociception. Both glial activation and proinflammatory cytokine induction underlie this communication. We investigated whether satellite glial cell (SGC) and tumor necrosis factor-α (TNF-α) activation in DRG participates in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat model of visceral hyperalgesia. In TNBS-treated rats, TNF-α expression increased in DRG and was colocalized to SGCs enveloping a given neuron. These SGCs were activated as visualized under electron microscopy: they had more elongated processes projecting into the connective tissue space and more gap junctions. When nerves attached to DRG (L6-S1) were stimulated with a series of electrical stimulations, TNF-α were released from DRG in TNBS-treated animals compared with controls. Using a current clamp, we noted that exogenous TNF-α (2.5 ng/ml) increased DRG neuron activity, and visceral pain behavioral responses were reversed by intrathecal administration of anti-TNF-α (10 μg·kg−1·day−1). Based on our findings, TNF-α and SGC activation in neuron-glial communication are critical in inflammatory visceral hyperalgesia.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of systemic glucose and insulin homeostasis; however, its exact role in adipocytes is poorly understood. This study was to elucidate the role of PTP1B in adipocyte differentiation and its implication in obesity. During differentiation of 3T3-L1 white preadipocytes, PTP1B decreased progressively with adipocyte maturation. Lentivirus-mediated PTP1B overexpression in preadipocytes delayed adipocyte differentiation, shown as lack of mature adipocytes, low level of lipid accumulation, and down-regulation of main markers (PPARγ2, SREBP-1c, FAS and LPL). In contrast, lentivirus-mediated PTP1B knockdown accelerated adipocyte differentiation, demonstrated as full of mature adipocytes, high level of lipid accumulation, and up-regulation of main markers. Dominant-negative inhibition on endogenous PTP1B by lentivirus-mediated overexpression of PTP1B double mutant in Tyr-46 and Asp-181 residues (LV-D/A-Y/F) also stimulated adipogenesis, more efficient than PTP1B knockdown. Diet-induced obesity mice exhibited an up-regulation of PTP1B and TNFα accompanied by a down-regulation of PPARγ2 in white adipose tissue. TNFα recombinant protein impeded PTP1B reduction and inhibited adipocyte differentiation in vitro; this inhibitory effect was prevented by LV-D/A-Y/F. Moreover, PTP1B inhibitor treatment improved adipogenesis and suppressed TNFα in adipose tissue of obese mice. All together, PTP1B negatively regulates adipocyte development and may mediate TNFα action to impair adipocyte differentiation in obesity. Our study provides novel evidence for the importance of PTP1B in obesity and for the potential application of PTP1B inhibitors.

To find out the status of HIV infection, sexual behaviors with both men and women as well as condom use among currently married men who have sex with men (MSM) so as to document for HIV intervention targeting this sub-population, in Beijing, Chengdu, Harbin and Zhengzhou cities."Snowballing" sampling method was used to recruit subjects in four cities. Participants were investigated by anonymous questionnaire containing demographics, sexual orientation, both homosexual and heterosexual behaviors and condom use during the past 6 months. Blood samples from participants were used to test HIV antibodies.Of the 858 participants for four cities, the average age was 38.3 (SD=9.1) years. 36.7% of them had completed the junior high school or under. The percentage of participants who identified themselves as homosexual, bisexual, and heterosexual or undecided were 40.9%, 54.3% and 4.8%, respectively. The overall HIV prevalence was 8.0%, and among four cities the HIV prevalence in Chengdu was the highest (13.3%). Results from the Multiple logistic regression analysis showed that never used condoms when having anal sex with men during the past 6 months among participants who did not have a city residential card, identifying himself as having homosexual orientation, living in Harbin, having first anal sex experience before 18 years of age the range of OR value was 1.5-2.1. In addition, the factors associated with never using condoms in vaginal sex with women during the past 6 months were as follows: being over 46 years old, not having a city residential card, living in Beijing, identifying himself as heterosexual orientated or with unknown sexual orientation, never using condoms in anal sex with men during the past 6 months, the range of OR value was 1.7-5.9.The prevalence of HIV infection seemed to be quite high among those currently married MSM. High rates of unprotected homosexual and heterosexual behaviors might accelerate the spreading of HIV from currently married MSM to their wives.

To investigate HIV and treponema pallidum infection status, risky sexual behavior among men who have sex with men (MSM) and its impact factors in China.Snowball sampling was used to recruit subjects from April to August in 2008 in Beijing, Harbin, Zhengzhou and Chengdu city. Serological test of HIV and treponema pallidum were conducted and a questionnaire survey was undertaken among subjects. The questionnaire included social demographics, characteristics of sexual partners and sexual behaviors.A total of 1693 subjects was enrolled in present study, which included 1390 MSM/M (82.1%) and 303 MSMW (17.9%). The infection rate of HIV among MSM/M and MSMW subjects were 7.0% (97/1390) and 6.6% (20/303), respectively. The infection rate of treponema pallidum among MSM/M and MSMW subjects were 11.9% (166/1390) and 13.2% (40/303), respectively. The proportions of MSM/M subjects who never used or sometimes used condoms when having same-sex anal intercourse in recent 6 months were 8.6% (120/1390), 45.3% (630/1390), respectively. The according proportions among MSMW subjects were 10.2% (31/303), 44.6% (135/303), respectively. Among MSM/M subjects, the risk factors of risk sexual behaviors included having less than 6 sexual partners (OR = 6.03, 95%CI: 2.54 - 14.28), no same-sex regular sexual partner (OR = 2.18, 95%CI: 1.30 - 3.65), no same-sex casual sexual partner (OR = 2.90, 95%CI: 1.79 - 4.71), T-pattern only during anal intercourse (OR = 1.64, 95%CI: 1.13 - 2.37) or P-pattern only (OR = 1.58, 95%CI: 1.04 - 2.41). Among MSMW subjects, the risk factors of same-sex risk sexual behaviors included having less than 6 sexual partners (OR = 12.95, 95%CI: 2.38 - 70.52), no same-sex regular sexual partners (OR = 0.42, 95%CI: 0.21 - 0.85), never used condom during heterosexual intercourse (OR = 3.53, 95%CI: 1.48 - 8.42).The infection rate of HIV and treponema pallidum among MSM subjects were quite high, and the same-sex risk sexual behaviors among MSM subjects were ubiquity, whose risk factors including having less than six of sexual partners, no same-sex casual sexual partner, T-pattern or P-pattern only during anal intercourse and never used condemn during heterosexual intercourse among MSMW subjects no same-sex regular partner was a risk factor in MSMS population, while having same-sex regular partners was a risk factor in MSMW population.

To understand the status of HIV infection and sexual behaviors with men and women among men who have sex with men and women (MSMW) and documented for HIV epidemic among men who have sex with men to the general population.300 participants were recruited by using "snowballing" sampling in Chengdu and Guangzhou, respectively. Participants completed the questionnaire and HIV test. The questionnaire included social demographic characteristics, number of male sexual partners, sexual behaviors and condom use in the past 6 months. Relations with female sexual partners, vaginal intercourse and condom use in the past 12 months were also studied.Of the 600 participants, the overall prevalence of HIV infection was 26.2% and the detection rate of HIV-positives in this survey was 8.5%. In the past 6 months 28.0% of the participants had 5 or more male sexual partners and the percentage of MSMW who had used condoms consistently during anal sex intercourse with men, was 44.2%. Of the participants, 52.3% had used condoms in the last three anal sex events and 63.0% in the last event. In the past 12 months, 86.0% of the participants who had vaginal sex with female partners and the proportions of MSMW who had wife, girlfriend, lover, female casual partner and female commercial partner were 65.0%, 27.2%, 1.5%, 12.7%, 4.5%, respectively. About a third of the MSMW had always used condoms when having vaginal sex in the past 12 month. In the last three vaginal sex events, the proportion of participants who had never used condoms was 36.5%. In the past 6 months, 55.7% of the MSMWs had used condoms consistently during anal sex with men in Chengdu, which was higher than those MSMW in Guangzhou (32.7%). In the past 12 months, the proportion of MSMW who had used condoms consistently during vaginal sex was 38.3%, which was higher than MSMW of Guangzhou (25.3%). Among those HIV-positive MSMWs, 91.1% had anal sex with men in the past 6 months and 49.7% HIV-positive MSMW had used condoms consistently during anal sex with men. The number of HIV-positive MSMW who had used condoms in the last or last three anal sex events with men, accounted for 60.5% and 69.4%, respectively. In the past 12 months, 82.8% of the HIV-positive participants had vaginal sex with women. Of the HIV-positive participants, 42.0% used condoms consistently and the percentage of HIV-positive MSMWs who used condom during last three vaginal sexes was 47.8%. In the past 6 months, the percentage (4.3%) of MSMW who were HIV-positive prior to the survey and never used condoms during anal sex with men was lower than the percentage (22.0%) of MSMW who were HIV-positive found in this survey. In the past 12 months 12.9% of the MSMW who were HIV positive prior to the survey never used condoms when having vaginal sex event, which was lower than MSMW (46.3%) who were HIV positive in this survey.The prevalence of HIV infection had reached a quite high level and with high rates of unprotected anal sex with men and vaginal sex with women among MSMWs, indicating that the inherent bridging aspect of MSMW might accelerate the spreading of HIV infection to the general population.

In the present work, in order to improve electron injection and transport at the interface of the hole blocking layer (HBL) and the electron transport layer (ETL) in the hole-domain solution processed phosphorescent organic light emitting devices (PhOLEDs), the mixed interface layer (MIL) was fabricated by partially co-doping hole blocking material 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) and electron transport material tris(8-quinolinolato) aluminum (Alq3) between HBL/ ETL. The MIL thickness was kept at 10nm, while the doping ratio of these two materials varied. Under a given electric field, the devices with the MIL at any mixed ratios all show much higher luminance and current density than those with a typical interface. For example, the luminance power and current density at 10 V for a typical device are 1.03 microW and 5.13 mA x cm(-2), while in case of mixed interface are 3.64 microW and 18.1 mA x cm(-2), respectively. From data results and theoretical analysis, the possible derivation of these improvements is considered to be the reduced electron accumulation at the interface resulting from the reduced electron injection energy barrier and lowered transport mobility by BCP material, which leads to an increase in electron amount in the emission layer and therefore the higher luminance and current density.

Bulk heterojunction polymer solar cells based on the blend of MEH-PPV (poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene]) and PCBM (1-(3-mehyloxycarbonyl)propyl-phenyl[6,6]C61) were fabricated. The thickness of the active layer was controlled by changing the concentration of MEH-PPV : PCBM (1 : 4 in weight ratio) solution and spin speeds. Investigation of the effects of active layer thicknesses on the performance of the photovoltaic devices indicates that, when the spin-coated speeds are lower than 4,000 r x min(-1) (round per minute), the open-circuit voltage (V(oc)) remains almost unchanged at approximately 0.8 V, whereas the short-circuit density (J(sc)) monotonically increases and the fill factor (FF) decreases slightly. The spin speeds that are higher than 5,000 r x min(-1) rpm result in the V(oc) and J(sc) both reduced. The V(oc) decreases from 0. 78 V at the spin-speed of 5,000 r x min(-1) to 0.67 V at 8,000 r x min(-1), and the J(sc) even decreases from 3.96 mA x cm(-2) at 5 000 r min(-1) to 1.76 mA x cm(-2) at 8,000 r x min(-1). J(sc) depends on the mutual impact of light absorption and carrier transport, while a contradicting effect from the two aspects is caused by varying the thickness of the active layer. The thicker the active layer, the more the excitons induced by light absorption. However, the build-in electric field becomes weaker and the pathway becomes longer for transporting the opposite charge carriers derived from exiciton separation to their corresponding electrodes at the same time, which makes the probability of charges collection by respective electrodes lower. With respect to the reduced V(oc), it may be attributed to the increased proportion of exciton dissociation at the interfaces of MEH-PPV and PCBM with the relevant electrodes.

With the development of organic light-emitting diodes, interests in the mechanisms of charge carrier photo generation, separation, transport and recombination continue to grow. Phosphorescent organic light-emitting diodes have gained considerable interest in the last 10 years because of high luminance efficiency. In the present paper, the authors investigated the optical and electrical characteristics of the devices based on Ir(ppy)3 and Ir(piq)3 doped PVK matrix emission layer at room temperature. The PL spectra show that the energy transfer from PVK to Ir(piq)3 is harder than that of PVK to Ir(ppy)3. The Luminescence characteristics of devices with different doping ratio show that it is not the energy transfer from matrix, but the recombination of injected carriers on phosphorescent molecules that is the main origin of EL emissions. From the viewpoint of energy level, the characteristics of carrier-trap and transport in Ir(piq)3 are better than in Ir(ppy)3 due to the high HOMO and low LUMO in Ir(piq)3.