The dynamic linkages among outbound tourism, economic growth, and international trade: empirical evidence from China.

The aim of this research was to examine the long- and short-run relationships among real expenditures on outbound tourism from China, economic growth and international trade for the period of 1995 to 2018, applying a newly developed cointegration test-the Bootstrap Autoregressive Distributed Lag framework. Evidence of cointegration was found when expenditures on outbound tourism served as the dependent variable, and economic growth and international trade were important factors affecting outbound tourism from China. For the short-run, a two-way Granger causality relationship was detected between economic growth and outbound tourism expenditures, and the feedback was confirmed between outbound tourism expenditures and international trade. The findings have important policy implications for the growth of the outbound tourism market. Large volumes of outbound tourists result in economic losses for China and outbound tourism reduces the growth of tourism-driven international trade.

Indigodole E from Strobilanthes cusia exhibits anti-IL-17A effect.

One new indazole alkaloid, indigodole E (1), was isolated from a traditional Chinese medicine Qing Dai prepared from the aerial parts of Strobilanthes cusia. The structure of 1 was elucidated by NMR, MS, UV, and IR spectra as well as optical rotation. Additionally, compound 1 could obviously inhibit not only IL-17A protein production at concentrations from 1.25 to 2.5 µg/mL, but also IL-17 gene expression at concentrations from 5.0 to 10.0 µg/mL without cytotoxicity toward Th17 and Jukat cells, respectively. Overall, indazole analogue 1 could be the anti-IL 17 A contributor of Qing Dai in this investigation.

Delta/Jagged-mediated Notch signaling induces the differentiation of agr2-positive epidermal mucous cells in zebrafish embryos.

Teleosts live in aquatic habitats, where they encounter ionic and acid-base fluctuations as well as infectious pathogens. To protect from these external challenges, the teleost epidermis is composed of living cells, including keratinocytes and ionocytes that maintain body fluid ionic homeostasis, and mucous cells that secret mucus. While ionocyte progenitors are known to be specified by Delta-Notch-mediated lateral inhibition during late gastrulation and early segmentation, it remains unclear how epidermal mucous cells (EMCs) are differentiated and maintained. Here, we show that Delta/Jagged-mediated activation of Notch signaling induces the differentiation of agr2-positive (agr2+) EMCs in zebrafish embryos during segmentation. We demonstrated that agr2+ EMCs contain cytoplasmic secretory granules and express muc5.1 and muc5.2. Reductions in agr2+ EMC number were observed in mib mutants and notch3 MOs-injected notch1a mutants, while increases in agr2+ cell number were detected in notch1a- and X-Su(H)/ANK-overexpressing embryos. Treatment with γ-secretase inhibitors further revealed that Notch signaling is required during bud to 15 hpf for the differentiation of agr2+ EMCs. Increased agr2+ EMC numbers were also observed in jag1a-, jag1b-, jag2a- and dlc-overexpressing, but not jag2b-overexpressing embryos. Meanwhile, reductions in agr2+ EMC numbers were detected in jag1a morphants, jag1b mutants, jag2a mutants and dlc morphants, but not jag2b mutants. Reduced numbers of pvalb8-positive epidermal cells were also observed in mib or jag2a mutants and jag1a or jag1b morphants, while increased pvalb8-positive epidermal cell numbers were detected in notch1a-overexpressing, but not dlc-overexpressing embryos. BrdU labeling further revealed that the agr2+ EMC population is maintained by proliferation. Cell lineage experiments showed that agr2+ EMCs are derived from the same ectodermal precursors as keratinocytes or ionocytes. Together, our results indicate that specification of agr2+ EMCs in zebrafish embryos is induced by DeltaC/Jagged-dependent activation of Notch1a/3 signaling, and the cell population is maintained by proliferation.

Measuring the Impact of Health on Economic Growth Using Pooling Data in Regions of Asia: Evidence From a Quantile-On-Quantile Analysis.

Health improvement has become a significant social priority since a moderately good human capital condition improves the workforce's abilities, efficiency, and quality of life. A rapid increase in healthcare expenditure is a trend in major developing and developed countries; however, healthcare expenditure widely varies among most Asian countries. Asian countries contribute a significant amount of output to economic development worldwide. The statistical test power is more efficient for the pooling of national data than individual national data because of the economic value and trade integration of regional nations. This is the first study that applies the quantile-on-quantile approach to investigate the influence of the quantiles of healthcare on the quantiles of the economy's growth for pooling forty countries in the Asian region. As the quantile of healthcare expenditure increases in the countries, the impact of healthcare expenditure on the economy's growth does not guarantee an increase. The positive and negative effects of healthcare expenditure on developing the economic relationship will repeatedly occur when the quantiles of the economy's growth increase in the countries. One implication is that the governments should account for problems such as corruption, bureaucracy, underinvestment, and inefficiency in health-related resource utilization.

Does tourism industry agglomeration reduce carbon emissions?

The global level of climate change agreement and the extensive development of China's industrialization process have caused China to face severe pressures regarding energy conservation and emission reduction. Tourism industry plays an important role in promoting steady economic growth and improving ecological environment in China. The agglomeration economic effect it produces can reduce carbon emissions, but the crowding effect may not be conducive to low carbon development. Therefore, how to reduce carbon emissions while promoting the development of tourism industry has become an urgent problem. This paper measures the level of tourism industry agglomeration and carbon emission in 30 regions of China and uses the method of spatial econometrics to analyze the impact of tourism industry agglomeration on carbon emissions. The empirical results prove that tourism industry agglomeration can reduce the carbon emissions of local and neighboring regions in China. However, this does not mean that the larger the scale of tourism industry agglomeration, the more conducive to the reduction of carbon emissions. For developed tourism groups, the impact of agglomeration effect on carbon emissions of local and adjacent areas shows a U-shaped relationship. When the agglomeration level exceeds 1.963, the expansion of agglomeration scale will increase local carbon emissions. For underdeveloped tourism areas, there is an inverted U-shaped relationship between agglomeration level and carbon emissions both in local and adjacent areas. When the agglomeration level reaches 1.883, the expansion of agglomeration scale will reduce local carbon emissions. The conclusions provide a basis for Chinese government to guide the low-carbon development of the tourism industry from another perspective.

Reliability of multi-purpose offshore-facilities: Present status and future direction in Australia.

Sustainable use of the ocean for food and energy production is an emerging area of research in different countries around the world. This goal is pursued by the Australian aquaculture, offshore engineering and renewable energy industries, research organisations and the government through the "Blue Economy Cooperative Research Centre". To address the challenges of offshore food and energy production, leveraging the benefits of co-location, vertical integration, infrastructure and shared services, will be enabled through the development of novel Multi-Purpose Offshore-Platforms (MPOP). The structural integrity of the designed systems when being deployed in the harsh offshore environment is one of the main challenges in developing the MPOPs. Employing structural reliability analysis methods for assessing the structural safety of the novel aquaculture-MPOPs comes with different limitations. This review aims at shedding light on these limitations and discusses the current status and future directions for structural reliability analysis of a novel aquaculture-MPOP considering Australia's unique environment. To achieve this aim, challenges which exist at different stages of reliability assessment, from data collection and uncertainty quantification to load and structural modelling and reliability analysis implementation, are discussed. Furthermore, several solutions to these challenges are proposed based on the existing knowledge in other sectors, and particularly from the offshore oil and gas industry. Based on the identified gaps in the review process, potential areas for future research are introduced to enable a safer and more reliable operation of the MPOPs.

IL-17A inhibitions of indole alkaloids from traditional Chinese medicine Qing Dai.

ETHNOPHARMACOLOGICAL RELEVANCE: Qing Dai, a famous traditional Chinese medicine (TCM), is prepared by a traditional fermentation process with the aerial part of Strobilanthes cusia. Currently, this TCM could treat various clinical inflammatory diseases, such as ulcerative colitis and psoriasis, however, the bioactive components of Qing Dai are unknown clearly. AIM OF THE STUDY: To isolate and identify the anti-IL-17A components of Qing Dai. MATERIALS AND METHODS: Silica, RP-18 gels, and size exclusion resin were used for column chromatography to isolate the pure compounds. The structures of isolates were elucidated by NMR, MS, UV, IR spectra, and optical rotation. IL-17A protein and gene expressions were also evaluated in the Th17 cell model and luciferase reporter assay, respectively. RESULTS: Two indole alkaloids, including one new indigodole D and cephalandole B, were isolated from Qing Dai. Indigodole D could inhibit IL-17A protein production during the Th17 polarization (EC50: 2.16 µg/mL) or after the polarization (EC50: 5.99 µg/mL) without cytotoxicity toward Th17 cells. Cephalandole B did not inhibit the IL-17A protein secretion. Nevertheless, both isolates notably inhibited IL-17A gene expression, especially cephalandole B, in a dose-dependent manner in Jukat cells with IL-17A luciferase reporter. CONCLUSIONS: Indole alkaloids, indigodoles A, C, D, tryptanthrin, and indirubin could contribute to anti-IL 17A properties of Qing Dai. The possible biogenetic mechanisms of above-mentioned indoles were also speculated in this investigation for further promising anti-IL-17 lead drugs development.

A Dynamic Relationship between Environmental Degradation, Healthcare Expenditure and Economic Growth in Wavelet Analysis: Empirical Evidence from Taiwan.

This paper analyzes the co-movement and causal linkages between environmental pollution and healthcare expenditure, taking economic growth as a control variable by using wavelet analysis for Taiwan over the period 1995 Q1-2016 Q4. The results show that there exists co-movement and causality between environmental pollution and healthcare expenditure at different frequencies and times. The changes in the relationships of the two variables are observed in certain events such as the period of the expansion stage, the policy of environmental pollution, and the issue of the National Health Insurance Integrated Circuit card (NHI-IC) in Taiwan. In the short-term, positive causality runs from healthcare expenditure to environmental pollution before 2004, while negative causality runs from healthcare expenditure to environmental pollution before 2007 in the long-term. After adding economic growth as a control variable, positive causality runs from healthcare expenditure to environmental pollution in the period 2009-2011 in the short-term, while negative causality running from healthcare expenditure to environmental pollution is shown in 2008 in the long-term. The results indicate that "higher government health expenditure leading to higher demand for environment quality" exists in different sub-periods and the argument may concern the factor of economics in the long-term. The positive healthcare lead in the short-term may be based on economics in the expansion stage. Also, the issue of NHI-IC possibly affects the dynamic relationship between healthcare expenditure and environmental pollution without considering economics. Based on empirical analysis, certain policy and managerial implications are addressed for decision-makers at macroeconomic and microeconomic levels.

Bootstrap ARDL on Health Expenditure, CO2 Emissions, and GDP Growth Relationship for 18 OECD Countries.

Using annual time-series data over the period 1975-2017, the researcher applied the bootstrap autoregressive-distributed lag (ARDL) cointegration model developed by McNown et al. (1) to examine whether there is a long run relationship among health expenditure, CO2 emissions, and gross domestic product (GDP) per capita in 18 Organization for Economic Cooperation and Development (OECD) countries. We find cointegration exists in Netherlands when real GDP per capita serves as a dependent variable, in New Zealand when health expenditure is the dependent variable, and in the United States when CO2 emissions are dependent variables. The main results show evidence of a short run relationship between the three variables. The empirical results support that there is a bidirectional causality between health expenditure and GDP growth for Germany and the United States, between CO2 emissions and GDP growth for Canada, Germany, and the United States, and between health expenditure and CO2 emissions for New Zealand and Norway. The results also indicate that there are unidirectional causality in other countries.

Investigation of the Co-Movement Relationship between Medical Expenditure and GDP in Taiwan-Based on Wavelet Analysis.

In this study, using the medical expenditures of the Taiwanese government and gross domestic product (GDP) as variables, the wavelet analysis method was used to empirically study the correlations and lead-lag relationships in quarterly data in the period from 1996 to 2016. In addition, the dependent population of the insured was used as the control variable. Results: After the dependent population was included as a control variable, there was a period of low- frequency (one to four years, short-term) linkage correlation, as well as a period of high- frequency (four to eight years, long-term) linkage correlation. In addition, for more than eight years, there was a high degree of linkage correlation, indicating that the linkage between medical expenditures and GDP occurred over the long- term. Moreover, since medical expenditures positively affected GDP, one-way causality was observed. However, after 2008, regardless of whether long or short- term was examined, there was almost no linkage correlation. Before 2008, the medical expenditures of the government were positively correlated with economic growth. After 2008, this effect had already disappeared. The universal health insurance system has long been denounced as a waste of medical resources. The government needs to find a new solution.

Indole alkaloids indigodoles A-C from aerial parts of Strobilanthes cusia in the traditional Chinese medicine Qing Dai have anti-IL-17 properties.

Qing Dai (Naturalis Indigo) is a traditional Chinese medicine (TCM) used as a topical agent in moderate psoriasis, targeting interleukin-17 (IL-17). In this study, it was prepared from the aerial parts of Strobilanthes cusia. Three undescribed indole alkaloid derivatives, indigodoles A-C, along with seven known compounds were isolated from this preparation of Qing Dai and their structures were elucidated from spectroscopic data, including NMR, MS, UV, IR, optical rotation, and CD. As well, most compounds were tested against IL-17. Indigodole C and tryptanthrin could significantly inhibit IL-17 production of Th17 cells. In addition, indigodole A and indirubin showed notably anti-IL-17 gene expression in dose-dependent effects without cytotoxicities toward Th17 and Jurkat cells, respectively. Overall, our studies indicate that the aforementioned indole alkaloids could contribute to anti-IL 17 properties of Qing Dai.

A Sketch of the Taiwan Zebrafish Core Facility.

In the past three decades, the number of zebrafish laboratories has significantly increased in Taiwan. The Taiwan Zebrafish Core Facility (TZCF), a government-funded core facility, was launched to serve this growing community. The Core Facility was built on two sites, one located at the National Health Research Institutes (NHRI, called Taiwan Zebrafish Core Facility at NHRI or TZeNH) and the other is located at the Academia Sinica (Taiwan Zebrafish Core Facility at AS a.k.a. TZCAS). The total surface area of the TZCF is about 180 m(2) encompassing 2880 fish tanks. Each site has a separate quarantine room and centralized water recirculating systems, monitoring key water parameters. To prevent diseases, three main strategies have been implemented: (1) imported fish must be quarantined; (2) only bleached embryos are introduced into the main facilities; and (3) working practices were implemented to minimize pathogen transfer between stocks and facilities. Currently, there is no health program in place; however, a fourth measure for the health program, specific regular pathogen tests, is being planned. In March 2015, the TZCF at NHRI has been AAALAC accredited. It is our goal to ensure that we provide "disease-free" fish and embryos to the Taiwanese research community.

The potential of lactulose and melibiose, two novel trehalase-indigestible and autophagy-inducing disaccharides, for polyQ-mediated neurodegenerative disease treatment.

The unique property of trehalose encourages its pharmaceutical application in aggregation-mediated neurodegenerative disorders, including Alzheimer's, Parkinson's, and many polyglutamine (polyQ)-mediated diseases. However, trehalose is digested into glucose by trehalase and which reduced its efficacy in the disease target tissues. Therefore, searching trehalase-indigestible analogs of trehalose is a potential strategy to enhance therapeutic effect. In this study, two trehalase-indigestible trehalose analogs, lactulose and melibiose, were selected through compound topology and functional group analyses. Hydrogen-bonding network analyses suggest that the elimination of the hydrogen bond between the linker ether and aspartate 321 (D321) of human trehalase is the key for lactulose and melibiose to avoid the hydrolyzation. Using polyQ-mediated spinocerebellar ataxia type 17 (SCA17) cell and slice cultures, we found the aggregation was significantly prohibited by trehalose, lactulose, and melibiose, which may through up-regulating of autophagy. These findings suggest the therapeutic applications of trehalase-indigestible trehalose analogs in aggregation-associated neurodegenerative diseases.

Trehalose attenuates the gait ataxia and gliosis of spinocerebellar ataxia type 17 mice.

Spinocerebellar ataxia type 17 (SCA17) is caused by CAG/CAA repeat expansion on the gene encoding a general transcription factor, TATA-box-binding protein (TBP). The CAG repeat expansion leads to the reduced solubility of polyglutamine TBP and induces aggregate formation. The TBP aggregation, mostly present in the cell nuclei, is distinct from that in most other neurodegenerative diseases, in which the aggregation is formed in cytosol or extracellular compartments. Trehalose is a disaccharide issued by the Food and Drug Administration with a Generally Recognized As Safe status. Lines of evidence suggest trehalose could prevent protein aggregate formation in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. In this study, we evaluated the therapeutic potential of trehalose on SCA17 using cerebellar primary and organotypic culture systems and a mouse model. Our results showed that TBP nuclear aggregation was significantly decreased in both the primary and slice cultures. Trehalose (4 %) was further supplied in the drinking water of SCA17 transgenic mice. We found both the gait behavior in the footprint analysis and motor coordination in the rotarod task were significantly improved in the trehalose-treated SCA17 mice. The cerebellar weight was increased and the astrocyte gliosis was reduced in SCA17 mice after trehalose treatment. These data suggest that trehalose could be a potential nontoxic treatment for SCA17.

The C-terminal region of G72 increases D-amino acid oxidase activity.

The schizophrenia-related protein G72 plays a unique role in the regulation of D-amino acid oxidase (DAO) in great apes. Several psychiatric diseases, including schizophrenia and bipolar disorder, are linked to overexpression of DAO and G72. Whether G72 plays a positive or negative regulatory role in DAO activity, however, has been controversial. Exploring the molecular basis of the relationship between G72 and DAO is thus important to understand how G72 regulates DAO activity. We performed yeast two-hybrid experiments and determined enzymatic activity to identify potential sites in G72 involved in binding DAO. Our results demonstrate that residues 123-153 and 138-153 in the long isoform of G72 bind to DAO and enhance its activity by 22% and 32%, respectively. A docking exercise indicated that these G72 peptides can interact with loops in DAO that abut the entrance of the tunnel that substrate and cofactor must traverse to reach the active site. We propose that a unique gating mechanism underlies the ability of G72 to increase the activity of DAO. Because upregulation of DAO activity decreases d-serine levels, which may lead to psychiatric abnormalities, our results suggest a molecular mechanism involving interaction between DAO and the C-terminal region of G72 that can regulate N-methyl-d-aspartate receptor-mediated neurotransmission.

Mechanical properties and buckling behaviors of condensed double-walled carbon nanotubes.

Molecular dynamics (MD) simulations are performed on condensed double-walled carbon nanotubes (CDWCNTs) to investigate the effects of compressed interwall spacings on their mechanical properties, in particular their buckling behavior under axial compression, torsion and bending. In CDWCNTs, the inner and outer nanotubes have diameters that are closer to each other than the nanotubes of conventional double-walled carbon nanotubes (DWCNTs). This leads to a smaller interwall spacing. The mechanical properties of the CDWCNTs, such as Young's modulus, interwall shear modulus, and the buckling strain under axial compression, torsion and bending are found to be greatly enhanced when compared with those of conventional DWCNTs. The enhancement is found to be inversely proportional to the interwall spacing.