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Gamma-aminobutyric acid (GABA), a non-protein-producing amino acid, is extensively found in microorganisms, plants and vertebrates, and is abundantly expressed in the spinal cord and brain. To date, GABA is considered to be the major inhibitory neurotransmitter in the central nervous system. Its physiological effects are related to the regulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of insomnia and depres-sion. Mediated through its specific receptors, it plays a pivotal role in the control of neuronal ex-citability, which can serve as anovel target for developing analgesics for pain management. This review provides an update on the accumulating evidence of specific GABA receptors and their subtypes in the involvement of pain analgesia.

BACKGROUND & AIMS Hepatic ischemia-reperfusion injury (IRI) is a common complication of hepatectomy and liver transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. The regulator of G-protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G-protein and mitogen-activated protein kinase (MAPK) signaling pathways. However, the role of RGS14 in hepatic IRI remains unclear. APPROACH & RESULTS We found that RGS14 expression increased in mice subjected to hepatic IR surgery and during hypoxia reoxygenation in hepatocytes. We constructed global RGS14 knockout (RGS14-KO) and hepatocyte-specific RGS14 transgenic (RGS14-TG) mice to establish 70% hepatic IRI models. Histological H&E staining, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), expression of inflammatory factors, and apoptosis were used to assess liver damage and function in these models. We found that RGS14 deficiency significantly aggravated IR-induced liver injury and activated hepatic inflammatory responses and apoptosis in vivo and in vitro. Conversely, RGS14 overexpression exerted the opposite effect of the RGS14-deficient models. Phosphorylation of transforming growth factor-β-activated kinase 1(TAK1) and its downstream effectors JNK and p38 increased in the liver tissues of RGS14-KO mice, but was repressed in those of RGS14-TG mice. Furthermore, inhibition of TAK1 phosphorylation rescued the effect of RGS14 deficiency on JNK and p38 activation, thus blocking the inflammatory responses and apoptosis. CONCLUSIONS RGS14 plays a protective role in hepatic IR by inhibiting the activation of the TAK1-JNK/p38 signaling pathway. This may be a potential therapeutic strategy for reducing incidences of hepatic IRI in the future.

Altricial birds often display biased preferences in providing parental care for their dependent offspring, especially during food shortages. During this process, such inflexible rules may result in provisioning errors. To demonstrate how parents optimize their provisioning strategies, we proposed a “diagnosis model” of parental care to posit that parents will undergo a diagnosis procedure to test whether selecting against some particular offspring based on phenotype is an optimal strategy. We tested this model in an asynchronous hatching bird, the Azure-winged Magpie Cyanopica cyanus, based on 10 years of data about demography and parental provisioning behaviors. Given their higher daily survival rates, core offspring (those hatched on the first day) merits an investment priority compared with their marginal brood mates (those hatched on later days). However, a marginal offspring also merited a priority if it displayed greater weight gain than the expected value at the early post-hatching days. Parents could detect such a marginal offspring via a diagnosis strategy, in which they provisioned the brood at the diagnosis stage by delivering food to every nestling that begged, then biased food toward high-value nestlings at the subsequent decision stage by making a negative response to the begging of low-value nestlings. In this provisioning strategy, the growth performance of a nestling became a more reliable indicator of its investment value than its hatching order or competitive ability. Our findings provide evidence for this “diagnosis model of parental care” wherein parents use a diagnosis method to optimize their provisioning strategy in brood reduction.

Objective In this study, we aimed to investigate the potential interaction of apatinib and buspirone and underlying mechanism. Methods UPLC-MS/MS assay was applied to determine the concentrations of buspirone and its main metabolites (1-PP and 6-OH buspirone) after incubated with liver microsomes. Moreover, the connection of in vitro and in vivo was further determined. Sprague Dawley rats were randomly divided into two groups: group A (20 mg/kg buspirone) and group B (buspirone vs 40 mg/kg apatinib). Tail vein blood was collected and subjected to the UPLC-MS/MS detection. Key findings Apatinib inhibited the generations of 1-PP and 6-OH buspirone dose-dependently with IC50 of 1.76 and 2.23 μm in RLMs, and 1.51 and 1.48 μm in HLMs, respectively. There was a mixed mechanism underlying such an inhibition effect. In rat, AUC(0–t), AUC(0–∞), Tmax and Cmax of buspirone and 6-OH buspirone increased significantly while co-administering with apatinib, but Vz/F and CLz/F decreased obviously while comparing group A with group B . Conclusions Apatinib suppresses the CYP450 based metabolism of buspirone in a mixed mechanism and boosted the blood exposure of prototype drug and 6-OH buspirone dramatically. Therefore, extra caution should be taken when combining apatinib with buspirone in clinic.

In altricial birds, to address which cues are used by parents to recognize their offspring, and when they switch between cues during reproduction, it has not been well determined. In this study, we address this question in a Tibetan population of the azure-winged magpie Cyanopica cyanus, by examining the dependence of parents on a nest’s spatial position in offspring recognition. During the egg and nestling phases, azure-winged magpie nests were translocated to new positions across various distances from their original site, and parental responses to the translocated nests were investigated. Our findings show that a nest’s spatial position is not connected with the survival of its young, but might be used as a cue in parental offspring recognition. When nests are translocated to a new position within a certain distance, parents could recognize their nests and returned to resume their parenting behaviors. Parental dependence on the nest’s spatial position in offspring recognition is higher during the egg phase than during the nestling phase, and it decreases with the growth of nestlings. After nestlings reach a certain age, the nest’ s spatial position was no longer used by parents as the single cue for offspring recognition. These findings suggest that azure-winged magpies switch their cues in offspring recognition during the different stages of reproduction. After parent–offspring communication has been established, the offspring’s phenotypic traits may become a more reliable cue than the nest’s spatial position in offspring recognition.

Sexual conflict in producing and raising offspring is a critical issue in evolutionary ecology research. Individual experience affects their breeding performance, as measured by such traits of provisioning of offspring and engagement in extra-pair copulations, and may cause an imbalance in sexual conflict. Thus, divorce is hypothesized to occur within aged social pairs, irrespective of current reproductive success. This concept was explored in the azure-winged magpie Cyanopica cyanus by investigating the divorce of a social pair and its relationship to their changes in breeding performance with prior experience. Females engaging in extra-pair copulation may intensify sexual conflicts and may be the main reason for divorce. Once divorced, females repairing with an inexperienced male realized higher reproductive success than that repairing with an experienced male; males repairing with an experienced female realized higher reproductive success than that repairing with an inexperienced female. This finding indicates that the fitness consequence of divorce depends on the breeding experience of new mates. Divorced females can obtain more extra-pair copulations, whereas divorced males cannot, when they repair with inexperienced breeders. Divorced females provisioned a brood at lower rates than inexperienced females whereas divorced males had no such difference. It appears that divorced females can obtain an advantage in sexual conflicts with inexperienced mates in future reproduction. Consequently, females are probably more active than males in divorcing their aged mates so as to select an inexperienced male as a new mate. Azure-winged magpies thus provide novel insights into the implications of sexual conflict in birds.

The unified modeling of distributed resources in comprehensive energy parks is the basis to achieving energy scheduling. This article first analyzed the key modeling elements of the energy storage model, the conversion of central air conditioning and ice storage to the energy storage model was completed. Finally, based on the unified energy storage model in combination with the time-of-use electricity prices and load conditions of the park, the local economic operation strategy of distributed resources was realized. The energy storage model and local operation strategy were used as the edge computing of the energy management gateway, which realized the real-time status monitoring and economic operation scheduling of the comprehensive energies. This study provides local solutions for the economic operation of comprehensive energy parks.

Pulmonary arterial hypertension (PAH) is defined as elevation of mean pulmonary arterial pressure to ≥25 mmHg within the low pressure pulmonary circulatory system. PAH is characterized by obstructive vascular remodeling, partially due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Puerarin is a natural flavonoid isolated from the herb Radix puerariae, which has been widely used for the treatment of cardiovascular and cerebrovascular disorders and diabetes. However, how puerarin mediates autophagy in the progression of pulmonary vascular remodeling is unclear. In this study, we explored the effects of puerarin in a hypoxic pulmonary hypertension (PH) rat model using immunohistochemistry, and morphometric analyses of right ventricle. In addition, cell counting kit 8 assay, western blotting and flow cytometry were employed to test cell proliferation in PASMCs, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and Western blot. We found that puerarin could alleviate hypoxia-induced PH in rats and improved pulmonary histopathology, and also reduced the expression of autophagy markers in vivo and in vitro. Moreover, puerarin also ameliorated hypoxia-induced PASMC proliferation in an autophagy-dependent manner. Overall, these findings demonstrated that puerarin could prevent hypoxia-induced PH in rats, possibly via reducing autophagy and suppressing cell proliferation. Keywords: Puerarin, Hypoxia, Pulmonary artery hypertension, Autophagy, Proliferation

Aim Regorafenib is a tyrosine kinase inhibitor that is mainly metabolized by CYP3A4. The genetic polymorphism of CYP3A4 would contribute to differences in metabolism of regorafenib. Previously, we had discovered several novel CYP3A4 variants. However, the catalytic characteristics of these 27 CYP3A4 variants on oxidizing regorafenib have not being determined. The purpose of this study was to investigate the catalytic characteristics of 27 CYP3A4 protein variants on the oxidative metabolism of regorafenib in vitro. Method Wild-type CYP3A4.1 or other variants was incubated with 0.5-20 μmol/L regorafenib for 30 minutes. After sample processing, regorafenib-N-oxide, a primary metabolite, was detected by ultra-performance liquid chromatography-tandem mass spectrometry system. Result CYP3A4.20 had no detectable enzyme activity compared with wild-type CYP3A4.1; five variants (CYP3A4.5, .16, .19, .24, .29) exhibited similar clearance value with CYP3A4.1; four variants (CYP3A4.14, .15, .28, .31) displayed increased enzymatic activities, while remaining variants showed markedly decreased intrinsic clearance values. Conclusion This study is the first to investigate the function of 27 CYP3A4 protein variants on the metabolism of regorafenib in vitro, and it may provide some valuable information for further research in clinic.

Oxidative stress following liver ischemia/reperfusion (I/R) is an important pathological mechanism responsible for liver injury. Veratric acid (VA) is a phenolic benzoic acid that has been reported to have antioxidant properties. However, whether VA has protective effects against liver I/R injury remains unclear. In the present study, a mouse liver I/R injury model was established. VA was administered intragastrically for one week before liver I/R. Biochemical indicators, histological analysis, cell apoptosis, oxidative stress, and pathway proteins were tested to evaluate the protective effects of VA on liver I/R injury. Furthermore, a mouse AML12 hepatocyte hypoxia/reoxygenation (H/R) model was used to explore the underlying mechanism. VA alleviated liver I/R injury, as manifested by decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrotic area, oxidative stress, and hepatocyte apoptosis. VA pretreatment increased the expression of Nrf2 and its downstream antioxidant proteins heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO-1). In addition, VA pretreatment increased AML12 cell activity and decreased oxidative stress; it also decreased the apoptosis induced by H/R. Moreover, the protective effect of VA on hepatocytes was related to the activation of the Nrf2 signaling pathway, and to increases in the Nrf2, HO-1, and NQO-1 protein expression. The inhibition of Nrf2 with ML385 offseted VA-mediated protection in AML12 cells. In conclusion, these results suggest that VA protects the liver from oxidative stress and apoptosis induced by liver I/R injury by activating the Nrf2 signaling pathway.

Background Great diversity exists in the parenting pattern of altricial birds, which has long been considered as an adaptive response to specific environmental conditions but not to their life-history style. Methods We examined the egg-laying and nestling-raising pattern of the Grey-backed Shrike (Lanius tephronotus) that breeds only once a year on the Tibetan Plateau. We compared the dietary composition to that of its sympatric competitor, the Brown-cheeked Laughing Thrush (Trochalopteron henrici) that breeds twice a year. Results Female Grey-backed Shrikes produced a fixed clutch size of five, with increasing egg size by their laying sequence. The last offspring in the brood is disadvantageous in the size hierarchy because it hatches later. However, they had the largest fledgling body mass. These findings indicate that Grey-backed Shrikes adopt the brood survival strategy in both the egg and nestling phases. Moreover, males and females exhibit no sexual division in providing parental care as they made an equal contribution to the total amount of food delivered to their brood. This parenting pattern of Grey-backed Shrikes, as well as their dietary items, differ significantly from those of the Brown-cheeked Laughing Thrush. Conclusions We suggest that the differentiation in life-history style between sympatric competitors, rather than a behavioral response to specific environmental conditions, plays a decisive role in driving avian parenting strategy diversification.

PER1 is a core component of the internal time-keeping system. In the suprachiasmatic nucleus, it serves as the primary circadian pacemaker in mammalian brains. PER1 functions with other clock components to generate a feedback loop involving the transcriptional repression of gene expression to produce a circadian rhythm with an approximately 24-hour cycle. Post-transcriptional modifications (PTMs) are a basic regulatory mechanism that both perpetuate self-sustained oscillations and interpret metabolic input into circadian physiology by affecting factors such as protein stability, interactions, localization, and activity. Here we examined whether the serine/threonine protein kinase WNK3, which is expressed in a circadian rhythm, can interact and colocalize with PER1 in the SCN. In rats, WNK3 knockdown in the SCN is associated with altered sleep patterns. Moreover, WNK3 can phosphorylate PER1 to promote its degradation and is associated with circadian oscillations when PER1 is expressed in vitro.

A kind of novel method of power allocation with limited cross-tier interference for cognitive radio network (CRN) is proposed in this paper. In this method, an interference-limited power allocation algorithm based on filter bank multi-carrier-offset quadrature amplitude modulation (FBMC-OQAM) is put forward. In order to improve the energy efficiency of the entire network and protect secondary users (SUs) in the network from too much interference, cross-tier interference limit is adopted, at the same time, virtual queue is designed to transform the extra packet delay caused by the contention for the channel of multi-user into the queuing delay. Taking the energy efficiency as the objective function, a nonlinear programming approach with nonlinear constraints is innovatively proposed under the constraints of time delay and transmission power. An iterative algorithm in order to solve the problem is also put forward. In the new algorithm, the fractional objective function is transformed into polynomial form, and the global optimal solution is obtained by iteration after reducing the computational complexity. In addition, a sub-optimal algorithm is proposed to reduce computational complexity. The experimental results show that the optimal algorithm has higher performance while the sub-optimal algorithm has a lower computational complexity. The presented method has very good practical importance for the CRN.

Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model. Fourteen studies comprising 3265 myopathy patients and 7743 controls were included. The summary ORs suggested that 521CC (OR: 2.31; 95% CI: 1.15–4.63; P = 0.019), 521TC (OR: 1.34; 95% CI: 1.02–1.76; P = 0.034), and 521CC + TC (OR: 1.82; 95% CI: 1.32–2.51; P

Aim To investigate the enzymatic properties of cytochrome P450 3A4 (CYP3A4) variants and their ability to metabolize vandetanib (VNT) in vitro, and to study potential drug interactions in combination with VNT. Method Recombinant CYP3A4 cell microsomes were prepared using a Bac-to-Bac baculovirus expression system. Enzymatic reactions were carried out, and the metabolites were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results The activities of 27 CYP3A4 variants were determined to assess the degree of VNT metabolism that occurred. Analysis indicated that there was enhanced intrinsic clearance (Vmax/Km, CLint) for eight variants (CYP3A4.2, 3, 9, 15, 16, 29, 32, and 33), while there was a significant decrease in CYP3A4.5, 7, 8, 10–14, 17–20, 23, 24, 28, 31, and 34. Compared with CYP3A4.1, no significant differences were found for CYP3A4.6 and 30. Furthermore, the relative clearances were compared between VNT and cabozantinib, which were all metabolized by CYP3A4 with the same indications. When combined with ketoconazole, which is a CYP inhibitor, obvious differences were observed in the potency of VNT between different variants, including CYP3A4.2, 15, and 18. Conclusion This comprehensive assessment of CYP3A4 variants provides significant insights into the allele-specific metabolism of VNT and drug interactions in vitro. We hope that these comprehensive data will provide references and predictions for the clinical application of VNT.

BACKGROUND: Primary membranous nephropathy (pMN) is the most common cause of nephrotic syndrome in adults. The discovery of the 2 autoantigens, M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A), has defined pMN as an autoimmune disease. A remarkable increase in the frequency of pMN in primary glomerular disease was witnessed in China. The genetic and environmental contributors to disease susceptibility have been investigated in these patients. SUMMARY: We reviewed recent publications in genetic and environmental studies of pMN, focusing mainly on those undertaken in China. Following a genome-wide association study, the gene-gene interaction between the 2 most significant risk factors, PLA2R1 and DQA1, was validated in Chinese patients with MN. Fine mapping on human leukocyte antigen (HLA) locus found that DRB1*1501 and DRB1*0301 were risk alleles. Three amino acid residues on positions 13 and 71 of HLA-DRβ1 chain may confer the susceptibility to pMN by presenting T-cell epitopes on PLA2R. Another study found that DRB3*0202 was the most likely culprit allele for the signal at DRB1*0301. One environmental risk factor for pMN has been identified as the long-term exposure to high levels of PM(2.5) in Chinese patients with MN. Each 10 μg/m(3) increase in PM(2.5) concentration was associated with 14% higher odds for pMN in the regions with PM(2.5) above 70 μg/m(3). KEY MESSAGE: A gene-environment interaction is suspected as an underlying mechanism for the increasing trend of pMN in China.

EZR, a member of the ezrin-radixin-moesin (ERM) family, is involved in multiple aspects of cell migration and cancer. SMYD3, a histone H3–lysine 4 (H3–K4)-specific methyltransferase, regulates EZR gene transcription, but the molecular mechanisms of epigenetic regulation remain ill-defined. Here, we show that antisense lncRNA EZR-AS1 was positively correlated with EZR expression in both human esophageal squamous cell carcinoma (ESCC) tissues and cell lines. Both in vivo and in vitro studies revealed that EZR-AS1 promoted cell migration through up-regulation of EZR expression. Mechanistically, antisense lncRNA EZR-AS1 formed a complex with RNA polymerase II to activate the transcription of EZR. Moreover, EZR-AS1 could recruit SMYD3 to a binding site, present in a GC-rich region downstream of the EZR promoter, causing the binding of SMYD3 and local enrichment of H3K4me3. Finally, the interaction of EZR-AS1 with SMYD3 further enhanced EZR transcription and expression. Our findings suggest that antisense lncRNA EZR-AS1, as a member of an RNA polymerase complex and through enhanced SMYD3-dependent H3K4 methylation, plays an important role in enhancing transcription of the EZR gene to promote the mobility and invasiveness of human cancer cells.

Display Omitted A new status box method is proposed to perform the stock trend prediction.A new feature construction approach for status box is presented.A new hybrid classifier that integrates AdaBoost algorithm, genetic algorithm and probabilistic support vector machine.The status box method can solve the unbalance problem of the stock turning points classification. Stock trend prediction is regarded as one of the most challenging tasks of financial time series prediction. Conventional statistical modeling techniques are not adequate for stock trend forecasting because of the non-stationarity and non-linearity of the stock market. With this regard, many machine learning approaches are used to improve the prediction results. These approaches mainly focus on two aspects: regression problem of the stock price and prediction problem of the turning points of stock price. In this paper, we concentrate on the evaluation of the current trend of stock price and the prediction of the change orientation of the stock price in future. Then, a new approach named status box method is proposed. Different from the prediction issue of the turning points, the status box method packages some stock points into three categories of boxes which indicate different stock status. And then, some machine learning techniques are used to classify these boxes so as to measure whether the states of each box coincides with the stock price trend and forecast the stock price trend based on the states of the box. These results would support us to make buying or selling strategies. Comparing with the turning points prediction that only considered the features of one day, each status box contains a certain amount of points which represent the stock price trend in a certain period of time. So, the status box reflects more information of stock market. To solve the classification problem of the status box, a special features construction approach is presented. Moreover, a new ensemble method integrated with the AdaBoost algorithm, probabilistic support vector machine (PSVM), and genetic algorithm (GA) is constructed to perform the status boxes classification. To verify the applicability and superiority of the proposed methods, 20 shares chosen from Shenzhen Stock Exchange (SZSE) and 16 shares from National Association of Securities Dealers Automated Quotations (NASDAQ) are applied to perform stock trend prediction. The results show that the status box method not only have the better classification accuracy but also effectively solve the unbalance problem of the stock turning points classification. In addition, the new ensemble classifier achieves preferable profitability in simulation of stock investment and remarkably improves the classification performance compared with the approach that only uses the PSVM or back-propagation artificial neural network (BPN).

Objective The aim of our study was to evaluate and compare the differences in the clinicopathological variables and overall survival (OS) of synchronous primary cancers of the endometrium and ovary (SCEO) and endometrial cancer with ovarian metastasis (ECOM). In addition, we aimed to determine the characteristics of and effective treatments for patients with SCEO to avoid misdiagnosis and overtreatment. Materials and methods A review of medical records from January 2009 to January 2017 revealed 111 patients with coexisting ovarian and endometrial carcinoma diagnosed at the Obstetrics and Gynecology Hospital of Fudan University. Clinicopathological variables were analysed using the Chi square test and Student’s t test. The survival rate was estimated using the Kaplan-Meier method, and statistical significance was analysed using the logarithmic rank test (univariate analysis). Results There were 51 cases of SCEO and 60 cases of ECOM. The mean age at diagnosis was 53.96 years and 55.41 years, respectively. There were no differences in age, menopausal status, BMI, CA125 level or complaints between the two groups. The 5-year survival rates were 58.8 and 36.7%, respectively (P

In the actual production applications and scientific research experiments, the process of the development, test, operation and application of a system will produce a large number of original data. And most of them are pulse type data. Normally, users can achieve to access the short pulse data in one time expediently. While for long pulse data, the requirement sometimes just need to read and analyze a certain segment of the long pulse data, and it also takes a lot of time to access all the data at once. So a data segmented processing software is designed and implemented in this paper for long pulse data. It provides convenience for users to view any segment of long pulse data in real time by the data decompressing and segmented processing process. The software is development by C++ programming language with a friendly interface. The key technologies are based on the open source lossless LZO compress and decompress algorithm, as well as a custom data segmentation algorithm. Now, the software has been tested and the results show that it can work stably and reliably.

Four new tetracyclic-type triterpenoids, jatrogossols A - D (1-4), along with 5 known analogues (5-9), were isolated from the ethanol extract of the branches and leaves of Jatropha gossypiifolia. The absolute configurations of 1-4 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicities of the triterpenoids were evaluated using RKO and HepG2 human cancer cell lines. Compound 8 was cytotoxic against RKO colon cancer cells with an IC50 value of 12.5 μM. The morphological features of apoptosis were evaluated in 8-treated RKO cells. Compound 8 effectively induced apoptosis of RKO, which was associated with G1 or S phase cell cycle arrest. Flow cytometric analysis showed that treatment with 8 significantly induced RKO cell apoptosis in a dose-dependent manner.

Background Human leukocyte antigen (HLA) alleles are implicated in drug-induced hypersensitivity, including by nevirapine and abacavir. The purpose of this meta-analysis was to evaluate the relationship between HLA polymorphisms and hypersensitivity to antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients. Methods We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library for studies that evaluated the associations of HLA polymorphisms with antiretroviral therapy-induced hypersensitivity published in April 2019. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were considered as estimates of the effect. Results The meta-analysis included 17 studies that assessed a total of 4273 patients. First, carriers of HLA-A *24 were associated with an increased risk of hypersensitivity among patients with HIV who received antiretroviral therapy (OR: 12.12; P = 0.018). Second, five SNPs of HLA-B genotypes, including *18 (OR: 1.63; P = 0.028), *35 (OR: 2.31; P = 0.002), *39 (OR: 11.85; P = 0.040), *51 (OR: 1.66; P = 0.028), and *81 (OR: 8.11; P = 0.021), were associated with an increased risk of hypersensitivity. Conversely, carriers of HLA-B *15 were associated with a reduced risk of hypersensitivity (OR: 0.43; P

Marine engineering equipment manufacturing is one of the most important industries in marine economy, which is listed as the marine strategic emerging industry. After the self-reliance development stage and the introduction of international standards and foreign technology, it is facing challenges to dedicate itself to international market competition. This article reviewed the development of marine engineering equipment manufacturing industry in China, analyzed the international competition situation and discussed the prospects. It is concluded that, marine engineering equipment manufacturing industry of China was undergoing transformation and upgrading stage with the trend towards deep water, large scale and automation in the world, strategies and actions were carried out from the top plan to the company level collaboration, it would make a fast increasing in the near future with the increasing international and domestic needs of deep sea exploit.

In bio-medical field, embedded numerous sensing nodes can be used to monitor and interact with physical world based on signal analysis and processing. Data from many different sources can be collected into massive data sets via localized sensor networks. Understanding the environment requires collecting and analyzing data from thousands of sensors monitoring, this is big data environment. The application of bio-medical image fusion for big-data computing has strong development momentum, big-data bio-medical image fusion is one of key problems, so the fusion method study is a hot topic in the field of signal analysis and processing. The existing methods have many limitations, such as large delay, data redundancy, more energy cost, low quality, so novel fusion computing method based on spherical coordinate for big-data bio-medical image of WSN is proposed in this paper. In this method, the three high-frequency coefficients in wavelet domain of bio-medical image are pre-processed. This pre-processing strategy can reduce the redundant ratio of big-data bio-medical image. Firstly, the high-frequency coefficients are transformed to the spherical coordinate domain to reduce the correlation in the same scale. Then, a multi-scale model product (MSMP) is used to control the shrinkage function so as to make the small wavelet coefficients and some noise removed. The high-frequency parts in spherical coordinate domain are coded by improved SPIHT algorithm. Finally, based on multi-scale edge of bio-medical image, it can be fused and reconstructed. Experimental results indicate the novel method is effective and very useful for transmission of big-data bio-medical image, which can solve the problem of data redundancy, more energy cost and low quality.

The epidemic of loperamide abuse and misuse in the patients for the alternative to opioids has become an increasing worldwide concern and has led to considerations about the potential for drug-drug interactions between loperamide and other combined drugs, especially inhibitors of cytochrome P450 (CYP450) enzymes, such as axitinib. This study assessed the effects of axitinib on the metabolism of loperamide and its main metabolite N-demethylated loperamide in rats and in rat liver microsomes (RLM), human liver microsomes (HLM) and recombinant human CYP3A4*1. The concentrations of both compounds were determined by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The exposures (AUC(0-t), AUC(0-∞) and Cmax) of loperamide and N-demethylated loperamide showed a conspicuous increase when loperamide was co-administered with axitinib. The Tmax of loperamide increased while CLz/F decreased under the influence of axitinib. In vitro, axitinib inhibited loperamide metabolism with the IC50 of 18.34 μM for RLM, 1.705 μM for HLM and 1.604 μM for CYP3A4*1, and it was confirmed as a non-competitive inhibitor in all enzymes. Taken together, the results indicated that axitinib had an obvious inhibitory impact on loperamide metabolism both in vivo and in vitro. Thus, more attention should be paid to the concurrent use of loperamide and axitinib to reduce the risk of unexpected clinical outcomes.