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Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers. Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10-300 mg [single dose]; 20-100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers. Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100-300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25-0.5 h post-dose and was maintained 48-168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20-100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/ mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups. Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development. [ABSTRACT FROM AUTHOR]

Accurate estimations of forest evapotranspiration (ET) and its components, transpiration (T) and evaporation (E), are important for deep understanding and predicting the responses of forest water cycles to climate change. In this study, the improved Shuttleworth-Wallace model (SWH) was applied to estimate ET, T, and E during 2003--2014 in a subtropical planation, and the modeled results were verified using in situ measurements by the eddy covariance technique, sap flow, and microlysimetermethod. The study aimed to clarify whether it is feasible and reliable to use the SWHmodel to estimate and partition ET in forests. In addition, depending on the long-term data, the specific performances in modeling ET under different climatic backgrounds were investigated, and the underlying mechanisms were explored. The results verified that the SWH performed relatively well in the subtropical forest, and the modeled ET, T and E could track the seasonal variations, although overestimations were found in the peak seasons. However, the model was relatively weaker in estimating the interannual variabilities. It performed well in modeling ET in normal years but showed larger model residuals in years with obvious climatic anomalies. In the severe summer-drought (2003) and cold-spring (2005) years, the model greatly overestimated ET. It also overestimated ET in summer since 2010, which may be ascribed to the less dependency of ET on VPD induced by the more humid microclimate in forest accompanied with forest development. For the ET partitioning results, the modeled and measured E and T values were all in reasonable ranges. The possible reasons for underestimations (overestimations) of E and T by measurements (SWH model) were discussed. In this study, the data obtained using different methods and from different scales matched each other and could be cross validated, and the discussion on discrepancies would be beneficial for understanding the advantages and flaws of differentmethods and could be the basis for optimizing themeasurement andmodel methods. In sum, this study verified that it is feasible to use the SWH model in forests and provided a basis for further improving and optimizing the modeled results under different climate backgrounds. [ABSTRACT FROM AUTHOR]

The transition from hunting and gathering to agricultural subsistence is a striking feature of the Neolithic revolution worldwide. Known as the cradle of a series of representative Neolithic cultures, south Hangzhou Bay (SHB) witnessed substantial changes in both landscape and human subsistence during the Holocene, yet the relationship between them was not well established. Here, we combined archaeobotanical results from sediment cores with archaeological findings to illustrate the subsistence changes during the Neolithic regime in the context of the landscape process in SHB. Our result showed that SHB was inundated by marine transgression 8,200 years ago without significant human imprints. At 8,200-7,600 cal yr. BP, the initial coastal wetland formation at locations with the semi-enclosed landscape would have facilitated the activities of hunting-gathering, incipient rice cultivation, and collecting seafood if accessible. Pollen and phytoliths evidence from multiple sediment cores in the Yaojiang Valley (YJV) suggested a desalinization process of wetland in the following hundreds of years. This amelioration of the environment had favored the intermittent rice cultivation at various locations in the YJV, where archaeological evidence was absent. Since 7,000-6,600 cal yr. BP, as freshwater wetland expanded with coastal progradation, a wide variety of food resources became available. Meanwhile, rice domestication began to serve as a crucial food supplement as evidenced by both microfossil results and archaeological findings. With the expansion of the coastal plain after 5,500 cal yr. BP, rice farming became widespread and rice consumption was increasingly important in the diet, as supported by discoveries of upgraded farming tools, abundant rice remains, and ancient rice paddies. Above all, the change of subsistence from hunting-gathering to rice farming exhibited an adaptive strategy in response to landscape evolution from an initial marine-influenced setting to a later coastal plain. [ABSTRACT FROM AUTHOR]

Ophiostomatalean fungi usually facilitate bark beetles to infest tree hosts and seriously endanger the health of coniferous forests. Tomicus pilifer Spessivtsev is a common endemic bark beetle in Asia and primarily threatens Pinus koraiensis. Tomicus species have similar morphology; however, they can be differentiated by their genetic characteristics through phylogenetic analyses. To date, the 28S rDNA sequence of T. pilifer and the diversity of ophiostomatalean fungi associated with T. pilifer have not been reported. In this study, we aimed to clarify the taxonomic status of T. pilifer and identify ophiostomatalean fungi associated with T. pilifer infesting P. koraiensis in northeastern China. In total, 315 ophiostomatalean fungal strains were isolated from 62 adults of T. pilifer and 220 tissue samples from T. pilifer galleries in Jilin Province. Thirty-five representative strains were further identified by comparing their morphological and physiological characteristics and conducting the phylogenetic analysis of ITS, ITS2-LSU, TUB2, and TEF1-a. We identified nine species of ophiostomatalean fungi belonging to four genera, which included six novel species (Ceratocystiopsis changbaiensis sp. nov., Leptographium linjiangense sp. nov., Leptographium qieshaoense sp. nov., Ophiostoma piliferi sp. nov., Ophiostoma tonghuaense sp. nov., and Ophiostoma yaluense sp. nov.), two previously described species (Graphilbum interstitiale and Ophiostoma fuscum), and one undefined specie (Ceratocystiopsis sp. 1). To the best of our knowledge, this is the first report of G. interstitiale and O. fuscum in China and the fungal diversity of ophiostomatalean in T. pilifer. The dominant species were O. piliferi and L. qieshaoense, representing 39.37% and 35.87% of the isolates, respectively. The results of this study provide valuable information on the symbiotic relationship between bark beetles and ophiostomatalean fungi. [ABSTRACT FROM AUTHOR]

Ips subelongatus is a major pest that infects larch plantations over large areas of northern and northeastern China. Ips species are closely associated with ophiostomatoid fungi that are morphologically well-adapted for dispersal by beetles. These associations result in important threat for coniferous forests worldwide. The aim of this study was to characterize the ophiostomatoid communities associated with I. subelongatus infesting Larix species and sympatric Pinus sylvestris var. mongolica in northeastern China forests. Morphological and multilocus phylogenetic approaches (based on six markers: ITS, LSU, 60S, β-tubulin, EF-1α, and CAL gene regions) allowed identifying 14 species of four genera (Ceratocystiopsis, Endoconidiophora, Leptographium and Ophiostoma). Eight species are showed to be new to science. Most strains resided in two Ophiostoma species complexes, viz. the O. clavatum and the O. ips complexes, all together accounting for 76.8% of all isolates. Ophiostoma hongxingense sp. nov., O. peniculi sp. nov., and O. subelongati sp. nov. (O. clavatum complex) and O. pseudobicolor sp. nov. (O. ips complex) were the four dominant species. The ophiostomatoid communities associated with larch bark beetles, I. cembrae and I. subelongatus, in Europe and Asia, China and Japan, also were compared. These comparisons showed distinct, specific assemblage patterns. [ABSTRACT FROM AUTHOR]

This study examines the impact of external economic policy uncertainty on the distribution of China's stock returns. The Chinese Economic Policy Uncertainty (CEPU) and global EPU (GEPU) indexes compiled by [1] are employed as a measurement of the external uncertainty. An empirical study is conducted using the GARCH-MIDAS framework. The first innovation of this study is extending the symmetric GARCHMIDAS model to the case of GJR; the leverage effect is therefore considered. The second innovation is considering the impact of EPU on the overall distribution of returns, rather than on the mean or volatility. Fullsample fitting shows that CEPU can explain around 14% of the return volatility, and CEPU together with GEPU can explain about 17%. Out-of-sample recursive forecasting demonstrates that it is meaningful to extend the models to GJR; the EPU information improves the return distribution forecasting. However, the impact of EPUs is limited, which implies that external uncertainty is quite different from the "internal" economic policy uncertainty directly driving the China's stock market. [ABSTRACT FROM AUTHOR]

The activity of the pine wood nematode Bursaphelenchus xylophilus leads to extremely serious economic, ecological and social losses in East Asia. The nematode causes pine wilt disease, which is currently regarded as the most important forest disease in China. The pathogenic nematode feeds on dendrocola fungi to complete its cycle of infection. As the vector of the nematode, the Japanese pine sawyer (Monochamus alternatus) also carries dendrocola fungi. Pine woods, infected by B. xylophilus and tunnelled by M. alternatus, are also inhabited by ophiostomatoid fungi. These fungi are well known for their association with many bark and ambrosia beetles. They can cause sapstain and other serious tree diseases. The aims of our study were to investigate and identify the ophiostomatoid communities associated with the epidemic pine wood nematode and the pine sawyer in Pinus massoniana and P. thunbergii forests, which are the main hosts of the pine wood nematode in China. Two hundred and forty strains of ophiostomatoid fungi were isolated from nematode and sawyer-infected trees in the coastal Shandong and Zhejiang Provinces, representing newly and historically infected areas, respectively. Six ophiostomatoid species were identified on the basis of morphological, physiological and molecular data. For the latter, DNA sequences of the internal transcribed spacer (ITS1-5.8S-ITS2) region and partial b-tubulin gene were examined. The ophiostomatoid species included one known species, Ophiostoma ips, three novel species, viz. Ophiostoma album sp. nov., Ophiostoma massoniana sp. nov. and Sporothrix zhejiangensis sp. nov. and two species whose identities are still uncertain, Ophiostoma cf. deltoideosporum and Graphilbum cf. rectangulosporium, due to the paucity of the materials obtained. The ophiostomatoid community was dominated by O. ips. This study revealed that a relatively high species diversity of ophiostomatoid fungi are associated with pine infected by B. xylophilus and M. alternatus in China. [ABSTRACT FROM AUTHOR]

Water-related ecosystem services (WESs) arise from the interaction between water ecosystems and their surrounding terrestrial ecosystems. They are critical for human well-being as well as for the whole ecological circle. An urgent service-oriented reform for the utilization and supervision of WESs can assist in avoiding ecological risks and achieving a more sustainable development in the Taihu Basin, China (THB). Spatially distributed models allow the multiple impacts of land use/land cover conversion and climate variation on WESs to be estimated and visualized efficiently, and such models can form a useful component in the toolbox for integrated water ecosystem management. The Integrated Valuation of Ecosystem Services and Tradeoffs model is used here to evaluate and visualize the spatio-temporal evolution of WESs in the THB from 2000 to 2010. Results indicate that water retention service experienced a decline from 2000 to 2005 with a recovery after 2005, while there was ongoing water scarcity in urban areas. Both the water purification service and the soil retention service underwent a slight decrease over the study period. Nutrients export mainly came from developed land and cultivated land, with the hilly areas in the south of the THB forming the primary area for soil loss. The quantity and distribution of WESs were impacted significantly by the shrinkage of cultivated land and the expansion of developed land. These findings will lay a foundation for a service-oriented management of WESs in the THB and support evidence-based decision making. [ABSTRACT FROM AUTHOR]

At present, there is limited research on the effect of climate change on the growth of trees in the Qinling Mountains, and the effect of altitude has rarely been considered. In order to accurately grasp the impact of climatic factors on the natural forest in this region, the effect of water and temperature conditions on the radial growth of Pinus armandii was studied according to dendroclimatology principles. Response function and multivariate regression methods were applied to study the response of the tree-rings, including earlywood width and latewood width, of P. armandii at three elevations (1600-1800, 1800-2000, 2000-2200 m) to climate change in this region. The results showed that the radial growth of P. armandii at the three elevations contained rich climatic information. The tree-ring widths at the three elevations were significantly negatively correlated with September temperature of the previous year and May temperature of the current year (P < 0.05) and were also negatively correlated with August precipitation of the previous year and May precipitation of the current year. The late-wood width of P. armandii at 1600-1800 m and 1800-2000 m was less sensitive to temperature and precipitation than that of the earlywood. The latewood width of P. armandii at 2000-2200 m was significantly negatively correlated with December temperature of the previous year and May temperature of the current year (P < 0.01), and was significantly and positively correlated with August precipitation of the previous year (P < 0.05). Characteristic analysis of the special years showed that large quantities of precipitation in September and October of the previous year were more likely to result in the formation of a very wide tree-ring. High spring and summer temperatures and less precipitation from April to June more likely resulted in the formation of extremely narrow tree-rings. Therefore, high precipitation in autumn of the previous year was conducive to the growth of P. armandii, whereas high temperature and drought in spring and summer inhibited the growth of P. armandii. [ABSTRACT FROM AUTHOR]

Although the relationships between street centrality and land-use intensity have been documented, only a few studies have explained the disparities in the global relationships among different land-use types or explored the local spatial relationships among such types. In this paper, the previously mentioned problem is addressed by investigating the main urban area ofWuhan, China. The street centrality indicators of closeness, betweenness, and straightness are expanded by considering the node-based weight of the road grade and road width. Land-use intensity is measured based on the building and economic activity density in the different land-use types. Kernel density estimation is used to convert the measures to a basic raster unit, whereas the geographically weighted regression (GWR) method is used to explore the spatial heterogeneity in the relationships. The results indicate strong relationships between street centrality and land-use intensity. Furthermore, the relationships vary not only among the different land-use types but also in the different categories of a single land-use type. Spatial heterogeneity also exists in these relationships. This finding confirms that street centrality plays a crucial role in shaping urban structure and land-use intensity, and understanding the formation of urban fabrics and the advancement of human civilization. [ABSTRACT FROM AUTHOR]

The Eastern Route of the South-to-North Water Diversion (SNWD-ER) project in China is a highly complex interbasin water-diversion system, which is constructed to pump, store, and supply water to support the rational water redistribution in China. This article presents the optimization modeling approach for the pricing and coordinating schemes of SNWDER project, and discusses the analysis results and their policy implications on the pricing and coordinating mechanisms in the SNWD-ER water-resource supply chain. For the government, formulating reasonable retail price upper bound is important to control the water resource wholesale price and retail price. Besides, various water-saving mechanisms can increase the price elasticity of water demand and affect the wholesale and retail prices. For the corporations, increasing the water resource production capacity and its supply will decrease the wholesale and retail prices. Furthermore, keeping enough initial water resource inventory by enhancing the rainfall using rate, and using 'free supply sources'-rainfall, or even some flooding sources can effectively decrease the wholesale and retail prices. Finally, for the end-users, enhancing the rainfall using rate can effectively decrease the wholesale and retail prices and reduce the energy consumption, which is good for the sustainable development and a low-carbon economy. [ABSTRACT FROM AUTHOR]

Appropriate fertilizer application is an important management practice to improve soil fertility and quality in the red soil regions of China. In the present study, we examined the effects of five fertilization treatments [these were: no fertilizer (CK), rice straw return (SR), chemical fertilizer (NPK), organic manure (OM) and green manure (GM)] on soil pH, soil organic carbon (SOC), total nitrogen (TN), C/N ratio and available nutrients (AN, AP and AK) contents in the plowed layer (0-20 cm) of paddy soil from 1998 to 2009 in Jiangxi Province, southern China. Results showed that the soil pH was the lowest with an average of 5.33 units in CK and was significantly higher in NPK (5.89 units) and OM (5.63 units) treatments (P<0.05). The application of fertilizers have remarkably improved SOC and TN values compared with the CK, Specifically, the OM treatment resulted in the highest SOC and TN concentrations (72.5% and 51.2% higher than CK) and NPK treatment increased the SOC and TN contents by 22.0% and 17.8% compared with CK. The average amounts of C/N ratio ranged from 9.66 to 10.98 in different treatments, and reached the highest in OM treatment (P<0.05). During the experimental period, the average AN and AP contents were highest in OM treatment (about 1.6 and 29.6 times of that in the CK, respectively) and second highest in NPK treatment (about 1.2 and 20.3 times of that in the CK). Unlike AN and AP, the highest value of AK content was observed in NPK treatments with 38.10 mg⋅kg-1. Thus, these indicated that organic manure should be recommended to improve soil fertility in this region and K fertilizer should be simultaneously applied considering the soil K contents. Considering the long-term fertilizer efficiency, our results also suggest that annual straw returning application could improve soil fertility in this trial region. [ABSTRACT FROM AUTHOR]

The article focuses on the establishment of pilot scheme of recycling and logistics systems for household electronic waste in Hangzhou, China. It recommends the need to increase capital investments to stimulate enterprises to develop green electronic information systems. These information systems include material research and development, product design, and pollutant discharge control during product manufacturing. It stresses the significance of improving the law and regulatory system, the operational standards and the resident's awareness of environmental protection.

In an attempt to obtain biologic control agents for grey mildew of tomato, a total of 628 bacterial strains were isolated from agricultural soil samples in Beijing, China, and screened for in vitro antibiosis toward Botrytis cinerea. Strain P94 exhibited the most obvious antagonistic activity. It P94 had no pathogenicity and was identified as Pseudomonas corrugata by the Biolog identification system combined with 16S rDNA sequence analysis and biochemical and physiologic characteristics. The specific products of polymerase chain reaction with two pairs of specific primers indicated that P94 belonged to P. corrugata genomic group II. Strain P94 inhibited the growth of a number of phytopathogenic fungal and bacterial species and showed inhibition activity to tomato grey mildew by tomato leaf testing in vitro. Strain P94 showed a positive reaction for HCN, protease, phosphatase, and indole acetic acid tests and a negative reaction for siderophore-, chitinase-, and cellulase-production tests. Therefore, the secondary metabolites producing novel P. corrugata strain P94 exhibited an innate potential of biocontrol activities in vitro. [ABSTRACT FROM AUTHOR]