Epidemiological and molecular characteristics of emergent dengue virus in Yunnan Province near the China-Myanmar-Laos border, 2013-2015.

BACKGROUND: Yunnan Province is located in southwestern China and neighbors the Southeast Asian countries, all of which are dengue-endemic areas. In 2000-2013, sporadic imported cases of dengue fever (DF) were reported almost annually in Yunnan Province. During 2013-2015, we confirmed that a large-scale indigenous DF outbreak emerged in cities of Yunnan Province near the China-Myanmar-Laos border. METHODS: Epidemiological characteristics of DF in Yunnan Province during 2013-2015 were evaluated by retrospective analysis. A total of 232 dengue virus (DENV)-positive sera were randomly collected for sequence analysis of the capsid/premembrane region of DENV from patients with DF in Yunnan Province. The envelope gene of DENV isolates was also amplified and sequenced. Phylogenetic analyses were performed using the neighbor-joining method with the Tajima-Nei model. RESULTS: Phylogenetically, all DENV-positive samples could be classified into DENV-1 genotype I and DENV-2 Asian I genotype during 2013-2015 and DENV-4 genotype I in 2015 from Ruili City; and DENV-3 genotype II in 2013 and DENV-2 Cosmopolitan genotype in 2015 from Xishuangbanna Prefecture. CONCLUSIONS: Our results indicated that imported DF from patients from Laos and Myanmar was the primary cause of the DF epidemic in Yunnan Province. Additionally, DENV strains of all four serotypes were identified in indigenous cases in Yunnan Province during the same time period, while the dengue epidemic pattern observed in southwestern Yunnan showed characteristics of a hypoendemic nature: circulation of DENV-1 and DENV-2 over consecutive years.

Syndrome Differentiation Analysis on Mars500 Data of Traditional Chinese Medicine.

Mars500 study was a psychological and physiological isolation experiment conducted by Russia, the European Space Agency, and China, in preparation for an unspecified future manned spaceflight to the planet Mars. Its intention was to yield valuable psychological and medical data on the effects of the planned long-term deep space mission. In this paper, we present data mining methods to mine medical data collected from the crew consisting of six spaceman volunteers. The synthesis of the four diagnostic methods of TCM, inspection, listening, inquiry, and palpation, is used in our syndrome differentiation. We adopt statistics method to describe the syndrome factor regular pattern of spaceman volunteers. Hybrid optimization based multilabel (HOML) is used as feature selection method and multilabel k-nearest neighbors (ML-KNN) is applied. According to the syndrome factor statistical result, we find that qi deficiency is a base syndrome pattern throughout the entire experiment process and, at the same time, there are different associated syndromes such as liver depression, spleen deficiency, dampness stagnancy, and yin deficiency, due to differences of individual situation. With feature selection, we screen out ten key factors which are essential to syndrome differentiation in TCM. The average precision of multilabel classification model reaches 80%.

[The current situation and strategies of snake antivenomimmunoglobulins research and development].

Snake antivenomimmunoglobulins are considered to be the most efficient drugs in snake envenomings. Most snake antivenomimmunoglobulins all over the world are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum till now. In this review, we retrospect the history of snake antivenomimmunoglobulins, analysis the present situation and pay the close attention on the key technological links in the process of research and manufacturing, such as properties of IgG and its fragments, selection and preparation of immunogen, optimization of immunization schedule and protein isolation and purification, which can be available for the reference in the research and development of snake antivenom.

An Improved Prioritized DDPG Based on Fractional-Order Learning Scheme.

Although deep deterministic policy gradient (DDPG) algorithm gets widespread attention as a result of its powerful functionality and applicability for large-scale continuous control, it cannot be denied that DDPG has problems such as low sample utilization efficiency and insufficient exploration. Therefore, an improved DDPG is presented to overcome these challenges in this article. Firstly, an optimizer based on fractional gradient is introduced into the algorithm network, which is conductive to increase the speed and accuracy of training convergence. On this basis, high-value experience replay based on weight-changed priority is proposed to improve sample utilization efficiency, and aiming to have a stronger exploration of the environment, an optimized exploration strategy for boundary action space is adopted. Finally, our proposed method is tested through the experiments of gym and pybullet platform. According to the results, our method speeds up the learning process, obtains higher average rewards in comparison with other algorithms.

Long-term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity.

INTRODUCTION: Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression. AIMS: This study aimed to identify changes in hippocampus synaptic plasticity under LSCS. METHODS: The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting. RESULTS: The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel. CONCLUSION: These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.

miR-9 modulates the expression of interferon-regulated genes and MHC class I molecules in human nasopharyngeal carcinoma cells.

The functions of miR-9 in some cancers are recently implicated in regulating proliferation, epithelial-mesenchymal transition (EMT), invasion and metastasis, apoptosis, and tumor angiogenesis, etc. miR-9 is commonly down-regulated in nasopharyngeal carcinoma (NPC), but the exact roles of miR-9 dysregulation in the pathogenesis of NPC remains unclear. Therefore, we firstly used miR-9-expressing CNE2 cells to determine the effects of miR-9 overexpression on global gene expression profile by microarray analysis. Microarray-based gene expression data unexpectedly demonstrated a significant number of up- or down-regulated immune- and inflammation-related genes, including many well-known interferon (IFN)-induced genes (e.g., IFI44L, PSMB8, IRF5, PSMB10, IFI27, PSB9_HUMAN, IFIT2, TRAIL, IFIT1, PSB8_HUMAN, IRF1, B2M and GBP1), major histocompatibility complex (MHC) class I molecules (e.g., HLA-B, HLA-C, HLA-F and HLA-H) and interleukin (IL)-related genes (e.g., IL20RB, GALT, IL7, IL1B, IL11, IL1F8, IL1A, IL6 and IL7R), which was confirmed by qRT-PCR. Moreover, the overexpression of miR-9 with the miRNA mimics significantly up- or down-regulated the expression of above-mentioned IFN-inducible genes, MHC class I molecules and IL-related genes; on the contrary, miR-9 inhibition by anti-miR-9 inhibitor in CNE2 and 5-8F cells correspondingly decreased or increased the aforementioned immune- and inflammation-related genes. Taken together, these findings demonstrate, for the first time, that miR-9 can modulate the expression of IFN-induced genes and MHC class I molecules in human cancer cells, suggesting a novel role of miR-9 in linking inflammation and cancer, which remains to be fully characterized.

Larvicidal activity of essential extract of Rosmarinus officinalis against Culex quinquefasciatus.

Constituents in rosemary (Rosmarinus officinalis) have been shown to have larvicidal activity against invertebrates. In order to explore the properties of crude extract of rosemary further, we studied the chemical composition and its activity against dichlorodiphenyltrichloroethane (DDT)-susceptible, DDT-resistant, and field strains of Culex quinquefasciatus larvae. The major components of R. officinalis were found to be eucalyptol and camphor, with relative percentages of 10.93% and 5.51%, respectively. Minor constituents included limonene, (+)-4-carene, isoborneol, 1-methyl-4-(1-methylethylidene)-cyclohexene, and pinene. The median lethal concentration (LC50) values of the essential oil of R. officinalis against DDT-susceptible, DDT-resistant, and field strains of larvae of Cx. quinquefasciatus were 30.6, 26.4, and 38.3 mg/liter, respectively. The single median lethal dose (LD50) in Kunming mice was 4752 mg/kg. Essential oils from R. officinalis may, therefore, provide an effective natural plant product for use in mosquito prevention and control.

[Genetic evolution analysis of matrix protein 2 gene of avian influenza H5N1 viruses from boundary of Yunnan province].

OBJECTIVE: To elucidate the variation in characterizations and genetic evolution of the matrix protein 2 or ion channel protein(M2) genes of avian influenza subtype H5N1 viruses in the boundary region of Yunnan province from 2008 to 2012. METHODS: A total of swab samples were collected from foreign poultry such as the junction between Yunnan and Vietnam, Laos,myanmar and wild birds in boundary region of Yunnan province from 2008 to 2012 and screened by H5N1 subtype-specific multiplex RT-PCR. The M genes of H5N1 virus from the positive samples were amplified by RT-PCR and cloned into pMD18-T vectors for sequencing. The alignment and phylogenetic analysis of M2 genes were performed with sequences of the known reference strains. RESULTS: A total of 71 positive samples were found out of 1240 samples and the positive rate was 5.72%. A total of 14 different M2 sequences were obtained from 30 positive samples and were divided into 3 distinct clades or sub-clades(1.2.1, 1.2.2 and 2) by phylogenetic analysis, 5, 7 and 2, respectively. The M2 genes and Hemagglutinin(HA) genes of H5N1 viruses from the boundary region of Yunnan province had showed different relationship of genetic evolution. The substitution or mutation of key amino acids sites had been found among the domains of epitope, adamantane-resistance, and poultry or human original viral strains. CONCLUSION: The M2 genes of H5N1 subtype viruses in boundary region of Yunnan province from 2008 to 2012 showed genetic divergence and the virus of clade 1.2.2 had become dominant epidemic strain in this region.

Composite robust control of uncertain nonlinear systems with unmatched disturbances using policy iteration.

In this paper, the composite robust control problem of uncertain nonlinear systems with unmatched disturbances is investigated. In order to improve the robust control performance, the integral sliding mode control method is considered together with H∞ control for nonlinear systems. By designing a disturbance observer with a new structure, the estimations of disturbances can be obtained with small errors, which are used to construct sliding mode control policy and avoid high gains. On the basis of ensuring the accessibility of specified sliding surface, the guaranteed cost control problem of nonlinear sliding mode dynamics is considered. To overcome the difficulty of robust control design caused by nonlinear characteristics, a modified policy iteration method based on sum of squares is proposed to solve the H∞ control policy of the nonlinear sliding mode dynamics. Finally, the effectiveness of the proposed robust control method is verified by simulation tests.

Weighted Gene Co-Expression Network Analysis to Explore Hub Genes of Resveratrol Biosynthesis in Exocarp and Mesocarp of 'Summer Black' Grape.

Resveratrol is a polyphenol compound beneficial to human health, and its main source is grapes. In the present study, the molecular regulation of resveratrol biosynthesis in developing grape berries was investigated using weighted gene co-expression network analysis (WGCNA). At the same time, the reason for the resveratrol content difference between grape exocarp (skin) and mesocarp (flesh) was explored. Hub genes (CHS, STS, F3'5'H, PAL, HCT) related to resveratrol biosynthesis were screened with Cytoscape software. The expression level of hub genes in the exocarp was significantly higher than that in the mesocarp, and the expressions of the hub genes and the content of resveratrol in exocarp peaked at the maturity stage. While the expression levels of PAL, CHS and STS in the mesocarp, reached the maximum at the maturity stage, and F3'5'H and HCT decreased. These hub genes likely play a key role in resveratrol biosynthesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further indicated that resveratrol biosynthesis was related to flavonoid biosynthesis, phenylalanine metabolism, phenylpropanoid biosynthesis, and stilbene biosynthesis pathways. This study has theoretical significance for exploring genes related to resveratrol biosynthesis in the exocarp and mesocarp of grapes, and provides a theoretical basis for the subsequent function and regulatory mechanism of hub genes.

Integrated metabolome and transcriptome analyses provide insight into the effect of red and blue LEDs on the quality of sweet potato leaves.

Red and blue light-emitting diodes (LEDs) affect the quality of sweet potato leaves and their nutritional profile. Vines cultivated under blue LEDs had higher soluble protein contents, total phenolic compounds, flavonoids, and total antioxidant activity. Conversely, chlorophyll, soluble sugar, protein, and vitamin C contents were higher in leaves grown under red LEDs. Red and blue light increased the accumulation of 77 and 18 metabolites, respectively. Alpha-linoleic and linolenic acid metabolism were the most significantly enriched pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 615 genes were differentially expressed between sweet potato leaves exposed to red and blue LEDs. Among these, 510 differentially expressed genes were upregulated in leaves grown under blue light compared with those grown under red light, while the remaining 105 genes were expressed at higher levels in the latter than in the former. Among the KEGG enrichment pathways, blue light significantly induced anthocyanin and carotenoid biosynthesis structural genes. This study provides a scientific reference basis for using light to alter metabolites to improve the quality of edible sweet potato leaves.

H∞ Codesign for Uncertain Nonlinear Control Systems Based on Policy Iteration Method.

In this article, the problem of H∞ codesign for nonlinear control systems with unmatched uncertainties and adjustable parameters is investigated. The main purpose is to solve the adjustable parameters and H∞ controller simultaneously so that better robust control performance can be achieved. By introducing a bounded function and defining a special cost function, the problem of solving the Hamilton-Jacobi-Isaacs equation is transformed into an optimization problem with nonlinear inequality constraints. Based on the sum of squares technique, a novel policy iteration algorithm is proposed to solve the problem of the H∞ codesign. Moreover, one modified algorithm for optimizing the robust performance index is given. The convergence and the performance improvement of new iteration policy algorithms are proved. Simulation results are presented to demonstrate the effectiveness of the proposed algorithms.

Event-Triggered Adaptive Control of Uncertain Nonlinear Systems With Composite Condition.

This article concentrates on the event-based collaborative design for strict-feedback systems with uncertain nonlinearities. The controller is designed based on neural network (NN) weights adaptive law. The controller and NN weights adaptive law are only updated at the triggering instants determined by a novel composite triggering threshold. Considering the conservativeness of event condition, the state-model error is integrated into constructing the composite condition and NN weights adaptive law. In the context of the proposed mechanism, the requirements of system information and the allowable range of event-triggering error are relaxed. The number of triggering instants is greatly reduced without deteriorating the system performance. Moreover, the stability of the closed-loop is proved by the Lyapunov method following time-interval and sampling instants. Simulation results show the effectiveness of the scheme proposed in this article.

Syndrome Differentiation of Chinese Medicine in Mars 500 Long-Term Closed Environment.

OBJECTIVE: To summarize and elucidate the characteristics and evolvement of Chinese medicine (CM) patterns reflecting the physical and mental conditions of participants in the Mars 500 long-term closed environment. METHODS: The DS01-T Digital TCM Four-Diagnostic Instrument and CM Inquiring Diagnostic Questionnaire were used to collect information from 6 participants in the Mars 500 International Joint Research Project, through diagnostic methods of observation, palpation and inquiry according to CM theory. During the 520 days of the experiment, data collection was performed 37 times; a total of over 400 digital images of tongues and facial complexion and over 20,000 data were collected. These data were then analyzed by a team of experts in CM, statistics, and data mining. RESULTS: The CM pattern evolvement of participants in the long-term closed environment followed some common trends. Qi deficiency was the main CM pattern observed, with individual features depending on constitutional differences [manifested in varying degrees of accompanying patterns of Gan (Liver) qi stagnation, Pi (Spleen) deficiency, dampness encumbering, or yin deficiency]. CONCLUSION: The research has verified the effectiveness of CM syndrome differentiation based on the four diagnostic methods, which should serve as a solid foundation for observation, monitoring, and intervention in regard to the health conditions of astronauts in long-term space flights in the future.

[Primary clinical result of digital template as navigation to supper cervical pedicle instrumentation].

OBJECTIVE: To observe the primary clinical result of digital template as navigation to the upper cervical pedicle instrumentation. METHODS: CT scan of upper cervical vertebrae was performed. 3-D model of upper cervical vertebrae was reconstructed by software Amira 3.1 and was preserved in STL format. Then 3-D model was run in software UG Imageware 12.0, the best pedicle channel was extracted according to the reverse engineering principle. A virtual navigational template was established according to he lamina anatomic trait, and the best pedicle channel. The virtual vertebrae and navigational template were manufactured using rapid prototyping. The navigational template was sterilized and used intra operative to assist with the placement of pedicle screw. The Accuracy of screw placement was confirmed with postoperative X-ray and CT scanning. RESULTS: The digital navigational template had been established and used in the 3 cases, the good trajectory of cervical pedicle had been showed by the CT scan of post operation. There were not complications of related pedicle screw insertion. CONCLUSIONS: A novel method of upper cervical pedicle location using Reverse Engineering and rapid prototyping has been developed; the navigational template is found to be highly accuracy and has great expectation.

Interferonalpha enhances etoposide-induced apoptosis in human osteosarcoma U2OS cells by a p53-dependent pathway.

Interferonalpha (IFNalpha) induces cell cycle arrest and triggers apoptosis and chemosensitivity. But the mechanism of IFNalpha in regulating chemosensitivity has not been fully understood. To study whether IFNalpha affected chemosensitivity of osteosarcoma cells, we treated p53-wild U2OS cells and p53-mutant MG63 cells with IFNalpha and etoposide, alone or in combination, and then examined growth inhibition, cell cycle arrest and apoptosis. IFNalpha enhanced etoposide-induced growth inhibition and apoptosis in p53-wild U2OS cells but not p53-mutant MG63 cells in a dose- and time-dependent manner. Etoposide-induced G2/M phase arrest was also enhanced by IFNalpha. The enhanced apoptosis was associated with the accumulation of transcriptionally active p53 accompanied with increased Bax and Mdm2, as well as decreased Bcl-2. IFNalpha also activated caspases-3, -8 and -9 protein kinases and PARP cleavage in response to etoposide in U2OS cells. Moreover, the combination-induced cytotoxicity and PARP cleavage were significantly reduced by caspase pan inhibitor and p53 siRNA. Thus we conclude that IFNalpha enhances etoposide-induced apoptosis in human osteosarcoma U2OS cells by a p53-dependent and caspase-activation pathway. The proper combination of IFNalpha and conventional chemotherapeutic agents may be a rational strategy for the treatment of human osteosarcoma with functional p53.

Quantization-Based Adaptive Actor-Critic Tracking Control With Tracking Error Constraints.

In this paper, the problem of adaptive actor-critic (AC) tracking control is investigated for a class of continuous-time nonlinear systems with unknown nonlinearities and quantized inputs. Different from the existing results based on reinforcement learning, the tracking error constraints are considered and new critic functions are constructed to improve the performance further. To ensure that the tracking errors keep within the predefined time-varying boundaries, a tracking error transformation technique is used to constitute an augmented error system. Specific critic functions, rather than the long-term cost function, are introduced to supervise the tracking performance and tune the weights of the AC neural networks (NNs). A novel adaptive controller with a special structure is designed to reduce the effect of the NN reconstruction errors, input quantization, and disturbances. Based on the Lyapunov stability theory, the boundedness of the closed-loop signals and the desired tracking performance can be guaranteed. Finally, simulations on two connected inverted pendulums are given to illustrate the effectiveness of the proposed method.

Amperometric phenol biosensor based on laponite clay-chitosan nanocomposite matrix.

A novel strategy to fabricate an amperometric biosensor for phenol determination based on chitosan/laponite nanocomposite matrix was described. The composite film was used to immobilize PPO on the surface of a glassy carbon electrode. Chitosan was utilized to improve the analytical performance of the pure clay-modified bioelectrode. The biosensor exhibited a series of properties: good affinity to its substrate (the apparent Michaelis-Menten constant for the sensor was found to be 0.16 mM), high sensitivity (674 mA M(-1)cm(-2) for catechol) and remarkable long-term stability in storage (it retains 88% of the original activity after 60 days). In addition, optimization of the biosensor construction as well as effects of experimental variables such as pH, operating potential and temperature on the amperometric response of the sensor were discussed.

Active Complementary Control for Affine Nonlinear Control Systems With Actuator Faults.

This paper is concerned with the problem of active complementary control design for affine nonlinear control systems with actuator faults. The outage and loss of effectiveness fault cases are considered. In order to achieve the performance enhancement of the faulty control system, the complementary control scheme is designed in two steps. Firstly, a novel fault estimation scheme is developed. Then, by using the fault estimations to reconstruct the faulty system dynamics and introducing a cost function as the optimization objective, a nearly optimal complementary control is obtained online based on the adaptive dynamic programming (ADP) method. Unlike most of the previous ADP methods with the addition of a probing signal, new adaptive weight update laws are derived to guarantee the convergence of neural network weights and the stability of the closed-loop system, which strongly supports the online implementation of the ADP method. Finally, two simulation examples are given to illustrate the performance and effectiveness of the proposed method.

Adaptive nearly optimal control for a class of continuous-time nonaffine nonlinear systems with inequality constraints.

The state inequality constraints have been hardly considered in the literature on solving the nonlinear optimal control problem based the adaptive dynamic programming (ADP) method. In this paper, an actor-critic (AC) algorithm is developed to solve the optimal control problem with a discounted cost function for a class of state-constrained nonaffine nonlinear systems. To overcome the difficulties resulting from the inequality constraints and the nonaffine nonlinearities of the controlled systems, a novel transformation technique with redesigned slack functions and a pre-compensator method are introduced to convert the constrained optimal control problem into an unconstrained one for affine nonlinear systems. Then, based on the policy iteration (PI) algorithm, an online AC scheme is proposed to learn the nearly optimal control policy for the obtained affine nonlinear dynamics. Using the information of the nonlinear model, novel adaptive update laws are designed to guarantee the convergence of the neural network (NN) weights and the stability of the affine nonlinear dynamics without the requirement for the probing signal. Finally, the effectiveness of the proposed method is validated by simulation studies.