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Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early stages can slow down disease progression. However, making an accurate diagnosis of PD at an early stage is challenging. Previous studies have revealed that even for movement disorder specialists, it was difficult to differentiate patients with PD from healthy individuals until the average modified Hoehn-Yahr staging (mH&Y) reached 1.8. Recent researches have shown that dysarthria provides good indicators for computer-assisted diagnosis of patients with PD. However, few studies have focused on diagnosing patients with PD in the early stages, specifically those with mH&Y ≥ 1.5. Method: We used a machine learning algorithm to analyze voice features and developed diagnostic models for differentiating between healthy controls (HCs) and patients with PD, and for differentiating between HCs and patients with mild PD (mH&Y ≥ 1.5). The models were independently validated using separate datasets. Results: Our results demonstrate that, a remarkable diagnostic performance of the model in identifying patients with mild PD (mH&Y ≥ 1.5) and HCs, with area under the ROC curve 0.93 (95% CI: 0.851.00), accuracy 0.85, sensitivity 0.95, and specificity 0.75. Conclusion: The results of our study are helpful for screening PD in the early stages in the community and primary medical institutions where there is a lack of movement disorder specialists and special equipment. [ABSTRACT FROM AUTHOR]

Heavy metal contamination in soils has worsened with rapid economic development. The combined method with principal component analysis/absolute principal component scores) and random forest models successfully reveals the total sources contribution structure and the specific influence process of industrial activities on heavy metals concentration in soils of the three urban agglomerations. Through statistical analysis, Cd in the Jing-Jin-Ji Metropolitan Region, Pb, Cu, Hg, Cd and As in the Yangtze River Delta, and Hg, As, Cd, Cu and Pb in the Pearl River Delta had relatively high mean concentrations and coefficient of variation (CV), which indicates that the contamination may be caused by human activities. Through PCA/APCS analysis, industrial activities contributed more than 60% of the Cd, Hg and Pb concentrations in soils in JJJ, YRD and PRD. A random forest simulation revealed that heavy metal pollution in soils is the combined result of natural processes and human activities in the three urban agglomerations. The heavy metals concentration in JJJ is mainly caused by industrial activities through land-based emission. The industrial activities presented more significant impact on heavy metals concentration in the soil of YRD compared with other two urban agglomerations. The elevation variation controlled the pattern of heavy metal concentration through influencing the spatial clustering feature of industrial activities. The distance from the sample location to the nearest industrial enterprise is the most important factor in determining the heavy metal concentration. The number of enterprises within a 5 km radius of the sample locations makes a greater contribution to the amount of Hg pollution than other heavy metals. The results of this study could provide support for better management of soil pollution prevention practices such as specific industrial governance and layout optimization. [ABSTRACT FROM AUTHOR]

The industrial wastewater accompanying rapid industrialization has caused severe pollution problems, especially in China. Addressing industrial structure upgrading and spatial optimization based on water environment carrying capacity has become an urgent issue. This paper establishes an analytical framework that uses a combination of economic and water environment information for industrial structure upgrading and spatial optimization based on water environment carrying capacity. This framework promotes the practical application of water environment carrying capacity theory for socio-ecological sustainability. The input-output table, information entropy method and a simulation platform of water environment carrying capacity using a multi-agent system are integrated into the analytical framework. A spatial assessment of the water environment carrying capacity, industrial structure upgrading and spatial optimization is performed for Changzhou, China. With the measures implementation of industrial structure upgrading and spatial optimization, the economic scale of the electrical equipment and machinery industry, which is the most important industry in Changzhou City, would reach 126,814.68 billion yuan, nearly 7.3 times its current value. In addition, the total local industrial economy would reach 3319.81 billion yuan, nearly 1.6 times its current scale. Due to the industrial concentration, the increased economic scale would create additional benefits, including the whole study region reaching the water quality goal and the water quality in urban areas significantly improving. The measures of industrial structure upgrading and spatial optimization would help to achieve a mutually beneficial balance between environmental protection and economic development. The analytical framework establishes the internal link between industrial structure upgrading and spatial optimization based on the water environment carrying capacity. The links from water quality to industrial structure upgrading and spatial optimization are also established. These connections could support the fine-scale management of water environments and could help local governments to plan sustainable socio-ecologic development. [ABSTRACT FROM AUTHOR]

Coastal zones are population and economy highly intensity regions all over the world, and coastal habitat supports the sustainable development of human society. The accurate assessment of coastal habitat degradation is the essential prerequisite for coastal zone protection. In this study, an integrated framework of coastal habitat degradation assessment including landuse classification, habitat classifying and zoning, evaluation criterion of coastal habitat degradation and coastal habitat degradation index has been established for better regional coastal habitat assessment. Through establishment of detailed three-class landuse classification, the fine landscape change is revealed, the evaluation criterion of coastal habitat degradation through internal comparison based on the results of habitat classifying and zoning could indicate the levels of habitat degradation and distinguish the intensity of human disturbances in different habitat subareas under the same habitat classification. Finally, the results of coastal habitat degradation assessment could be achieved through coastal habitat degradation index (CHI). A case study of the framework is carried out in the Circum-Bohai-Sea-Coast, China, and the main results show the following: (1) The accuracy of all land use classes are above 90%, which indicates a satisfactory accuracy for the classification map. (2) The Circum-Bohai-Sea-Coast is divided into 3 kinds of habitats and 5 subareas. (3) In the five subareas of the Circum-Bohai-Sea-Coast, the levels of coastal habitat degradation own significant difference. The whole Circum-Bohai-Sea-Coast generally is in a worse state according to area weighting of each habitat subarea. This assessment framework of coastal habitat degradation would characterize the landuse change trend, realize better coastal habitat degradation assessment, reveal the habitat conservation tendency and distinguish intensity of human disturbances. Furthermore, it would support for accurate coastal zone protection measures for the specific coastal area. [ABSTRACT FROM AUTHOR]

Cross-Strait economic activities are no longer unidirectional. The Taiwanese government opened the doors to Chinese investment in 2009. This paper addresses the following crucial question: What is the impact of Chinese investment on Taiwan's high-technology industrial development? Two further questions immediately follow: Will Chinese investment put Taiwanese industrial development at risk? Will an influx of Chinese investment lead to a turning point for Taiwanese industry? The paper first reviews Chinese investment in Taiwan under the framework of the Economic Cooperation Framework Agreement (ECFA) and then explains why we have chosen to focus here on the high-technology industry in Taiwan. It then outlines the main elements of Chinese outward foreign direct investment (OFDI) before seeking to answer the above research questions. Fieldwork for this paper was conducted from December 2014 to March 2016. Interviewees include Chinese investors, along with consultants from a Taiwanese institute created to promote industrial development. [ABSTRACT FROM AUTHOR]

This paper established a simulation platform for human-environment systems based on multiagent systems for water environment carrying capacity research. The platform's purpose is to study and present the water environment carrying capacity from four dimensions, i.e., Scale, Structure, Pattern and Technology. The framework is presented according to the standard Overview, Design concepts, Details protocol. The modeling functions from the four dimensions are demonstrated via a case application in Changzhou City of the Taihu Lake region, China. We compared this platform with previous research methods of determining the water environment carrying capacity research. The comparison shows that the uniqueness of the platform lies in its ability to reveal the water environment carrying capacity from the four dimensions and provide detailed and various routes for human-environment sustainability. The framework could be applied to research on any type of human-environment system. • A simulation platform has been established for human-environment research. • The platform realizes panoramic portrait of water environment carrying capacity. • The simulation platform is presented according to the standard ODD protocol. • The simulation results could support for human-environment sustainability. • The platform could support for research of any type of human-environment systems. [ABSTRACT FROM AUTHOR]

Intermuscular bones (IBs) are ubiquitous in most of freshwater farmed fishes, especially in cyprinid species, and the creation of IB-free mutants has become a hot issue in fish genetic breeding because of the potential beneficial for consumers and fish processing industry. Recently, significant progress in the mechanism underlying IB development has been achieved in zebrafish and a decisive player, runt-related transcription factor 2b (runx2b), has been identified. However, its role has not yet been validated in other farmed fishes. Amphitriploid gibel carp (Carassius gibelio) is an important aquaculture species in China, but the injuries threats with approximately 80 IBs have strongly restricted its industry development. In this study, we first identified two homeologs of runx2b (Cgrunx2b-A and Cgrunx2b-B) in gibel carp with about 91.8% identity, each of them possessing three alleles with 99.6% identities. Then, we traced the IB ossification process. Alizarin red S staining showed that gibel carp IB began to ossify at 14 approximately days post hatching (dph) and developed from the posterior to the anterior regions. Cgrunx2b-A and Cgrunx2b-B displayed similar expression pattern but differential expression level during IB development. Moreover, we applied an optimized protocol of CRISPR/Cas9 editing in the polyploid Carassius complex to disrupt the functions of Cg Runx2b-A and Cg Runx2b-B singly or simultaneously. IB development was unaffected by single deficiency of Cg Runx2b-A or Cg Runx2b-B, but simultaneous disruption of all alleles of both Cg Runx2b-A and Cg Runx2b-B leads to complete loss of IB. The results indicate that Cg Runx2b-A and Cg Runx2b-B cooperatively regulate IB development. Importantly, we created several gynogenetic gibel carp mutants, including IB-free Cgrunx2b-A −/−/− ; Cgrunx2b-B −/−/− mutants and IB-less Cgrunx2b-A −/−/− ; Cgrunx2b-B −/−/+ mutants. The current study not only confirms the cooperatively decisive role of two homeologs of runx2b in IB formation, but also provides a feasible gene editing-based approach to create IB-free mutants in gibel carp. • Cgrunx2b-A and Cgrunx2b-B cooperatively regulate intermuscular bone (IB) development in amphitriploid gibel carp. • Single loss of Cg Runx2b-A or Cg Runx2b-B function is unable to affect normal development of intermuscular bones. • Simultaneous disruption of all alleles of both Cg Runx2b-A and Cg Runx2b-B create IB-free gibel carp mutants. [ABSTRACT FROM AUTHOR]

Viperin is increasingly thought as a key protein in antiviral response. However, the in vivo antiviral effects of fish viperin remains unresolved. Hexaploid gibel carp (Carassius gibelio) is an important aquaculture species in China and its culture industry has suffered enormous economic losses due to an epizootic disease caused by C. auratus herpesvirus (Ca HV) since 2012. In our previous studies, two duplicated viperin homeologs (Cgviperin-A and Cgviperin-B) were identified and their divergent antiviral mechanisms were revealed through in vitro overexpression in CAB (C. auratus blastulae embryonic) cell. Here, we tried to explore their function difference in vivo by using CRISPR/Cas9 editing. Firstly, we uncovered their biased expression patterns and differential promoter activities. Then we mutated them singly or simultaneously in resistant clone H of gibel carp by using CRISPR/Cas9 and finally confirmed that they cooperatively participated in the antiviral battle between gibel carp and Ca HV through virus challenge and comparative transcriptome analysis. Cg Viperin-A depletion mainly affected immune-related pathways and Cgviperin-B deficiency influenced autophagy-associated pathways. Simultaneous disruption of them resulted in complete loss of resistance ability of gibel carp against Ca HV. Significantly, the deficiency of Cgviperin-A influenced the expression of Cgviperin-B in Cgviperin-A −/−/− mutant, but Cgviperin-A transcripts kept a high level of expression in the Cgviperin-B −/−/− mutant, same as in the WT. Therefore, the current findings are not only the first time to clarify the antiviral activities of Viperin in the battle between teleost and virus in vivo, but also explain the detailed evolutionary divergence of a duplicated gene in a recurrent polyploid fish. • Two duplicated viperin homeologs were edited singly or simultaneously in hexaploid gibel carp by using CRISPR/Cas9. • It is the first time to clarify the antiviral activities of Viperin in the battle between teleost and virus in vivo. • Cg Viperin-A and Cg Viperin-B have sub-functionalized, Cg viperin-B has evolved a novel function related to autophagy. • Cg Viperin-A and Cg Viperin-B cooperatively participate in the antiviral response of gibel carp against CaHV. [ABSTRACT FROM AUTHOR]

Regional ecological quality is largely affected by human activities, which restricts the sustainable development of regional economy. Taking the China-Laos railway economic belt as an example, we investigated the effects of human activities on ecological quality. The remote sensing images of 1999, 2009 and 2019 were selected to calculate remote sensing ecological index (RSEI). Spatial autocorrelation statistics and local G statistics were used to explore the spatial-temporal variations of ecological quality in the study area. Combined with the population density in the same period, a geographically weighted regression model was constructed to quantitatively analyze the ecological effects of different human activity intensities in the study area. The results showed that the ecological quality in the study area presented a trend of increasing firstly and then decreasing later from 1999 to 2019, and that the mean value of RSEI varied from 0.645 (1999) to 0.738 (2009) and then decreasing to 0.721 in 2019. Specially, the ecological quality fluctuated more apparently in the midlands. The results of fitting population density and ecological quality based on geographical weighted regression model (GWR) were significantly better than that of least square method. R 2 of different periods based on GWR was higher than 0.7 and the fitting effect was stable. The fitting degree of GWR in 2019 was the best ( R in 1999 and 2009 were 0.726 and 0.754, respectively. The ecological quality along the China-Laos railway south area (such as Vientiane) was more sensitive to human activities, with most of these places belonged to moderately sensitive regions. For the highly, moderately and lowly ecological sensitive regions, every 10, 100, 1000-fold increases in population density would lead to a decrease of 0.2, 0.4 and 0.6 to the mean value of RSEI in turn. The development of economic belt would increase population density. During the planning and layout of economic belt, human activities should be controlled to avoid the deterioration of ecological quality in the potential and current sensitive regions.2 was 0.785), and R 2 in 1999 and 2009 were 0.726 and 0.754, respectively. The ecological quality along the China-Laos railway south area (such as Vientiane) was more sensitive to human activities, with most of these places belonged to moderately sensitive regions. For the highly, moderately and lowly ecological sensitive regions, every 10, 100, 1000-fold increases in population density would lead to a decrease of 0.2, 0.4 and 0.6 to the mean value of RSEI in turn. The development of economic belt would increase population density. During the planning and layout of economic belt, human activities should be controlled to avoid the deterioration of ecological quality in the potential and current sensitive regions.

Soil is a fundamental carrier to support for human living and development and has been polluted seriously by heavy metals. This fact highlights the urgency to realize soil heavy metal pollution prevention through soil heavy metals contamination status assessment and root cause analysis. The previous research tends to focus status assessment and source identification without consideration of economic aspect. This study realized the systematic analysis from status assessment, sources identification and economic-environmental cost-benefits analysis in the Yangtze River basin. Through the spatial difference comparison among the provinces of upper, middle and lower in the Yangtze River basin, it revealed that anthropogenic influence is the main reason caused the current Cd contamination in Yangtze River basin. An interesting finding is that the human caused Cd concentration contribution amount is nearly the same between upstream and downstream which is all about 0.1 mg/kg, while they have quite different economic scale. It indicated that due to the difference of the scale and structure of local economy, and the level of cleaner production and pollution treatment, some regions could own high economic-benefits and low environmental cost, which it is opposite in other regions. The geographic location and natural resources is the root cause to form the environmental cost-economic benefits difference among regions. The convenient traffic promoted downstream to develop large amount and high quality of economy. The natural mineral resources promoted midstream to develop resources based economy. The poor condition of traffic and natural resources has restricted the development of Qinghai province, and made it has the highest Cd pollution intensity. The results would provide effective economic management measures for better soil quality and sustainable development goals achievement., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Linking water to research on coupled human and natural systems (CHANS) has attracted wide interest as a means of supporting human-natural sustainability. However, most current research does not focus on water environmental properties; instead, it is at the stage of holistic status assessment and measures adjustment from the point of view of the whole study region without revealing the dynamic interaction between human activities and natural processes. This paper establishes an integrated model that combines a System Dynamics model, a Cell Automaton model and a Multiagent Systems model and exploits the potential of the combined model to reveal regions' human-water interaction status during the process of urban evolution, identify the main pollution sources and spatial units, and provide the explicit space-time measurements needed to enhance local human-natural sustainability. The successful application of the integrated model in the case study of Changzhou City, China reveals the following. (1) As the city's development has progressed, the water environment status in some spatial units is still unsatisfactory and may even become more serious, especially in the urban areas of the Urban District and Liyang County. The concentration of Chemical Oxygen Demand (COD) in monitoring section 157 of the Urban District has increased from 36.90 mg/l to 40.84 mg/l. The main source of this increase is the increase in secondary industry. (2) With the application of the spatially explicit measures of the sewage treatment ratio improvement and new sewage plant construction, the water quality in the urban area has significantly improved and now satisfies the water quality standards. The measure of livestock manure utilization enhancement is adopted to improve the spatial units in which livestock is the main pollution source and achieve the goal of water quality improvement. The model can be used to support the sustainable status assessment of human-water interaction and to identify effective measures that can be used to realize human-water sustainability along with social-economic development., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Most vertebrates reproduce sexually, and plastic sex determination mechanisms including genotypic sex determination (GSD) and environmental sex determination (ESD) have been extensively revealed. However, why sex determination mechanisms evolve diversely and how they correlate with diverse reproduction strategies remain largely unclear. Here, we utilize the superiority of a hexaploid gibel carp (Carassius gibelio) that is able to reproduce by unisexual gynogenesis and contains a rare but diverse proportion of males to investigate these puzzles. A total of 2248 hexaploid specimens were collected from 34 geographic wild populations throughout mainland China, in which 24 populations were revealed to contain 186 males with various incidences ranging from 1.2 to 26.5%. Subsequently, the proportion of temperature-dependent sex determination (TSD) was revealed to be positively correlated to average annual temperature in wild populations, and male incidence in lab gynogenetic progenies was demonstrated to increase with the increasing of larval rearing temperature. Meanwhile, extra microchromosomes were confirmed to play genotypic male determination role as previously reported. Thereby, GSD and TSD were found to coexist in gibel carp, and the proportions of GSD were observed to be much higher than that of TSD in sympatric wild populations. Our findings uncover a potential new mechanism in the evolution of sex determination system in polyploid vertebrates with unisexual gynogenesis ability, and also reveal a possible association of sex determination mechanism transition between TSD and GSD and reproduction mode transition between unisexual gynogenesis and bisexual reproduction.

Polyploidy roles on adaptive evolution and ecological novelty have been extensively studied in plants but remained unclear in vertebrates owing to the rare polyploidy incidences. Here, a huge number of 3105 specimens in Carassius species complex including 2211 hexaploids and 894 tetraploids were sampled from 34 locations through mainland China. And hexaploids had wider geographic distribution than tetraploids especially in the areas with high altitude, high latitude and low annual precipitation. Then, an approximate 1050 bp transferrin (tf) fragments were amplified from all the samples, and 526 tf alleles were identified from a total of 37260 sequences at last. Intriguingly, higher nucleotide diversity of tf alleles in hexaploids than in tetraploids was revealed. Moreover, via phylogenetic analysis of tf alleles, potential origin center of Carassius species complex was deduced to be Yangtze River basin and hexaploids should undergo multiple independent polyploidy origins from sympatric tetraploids. These findings indicate that the hexaploids might possess stronger environmental adaptation and ecological novelty than the tetraploids, which provide an association paradigm of recurrent polyploidy and ecological context in polyploid vertebrates.

Aim: To look for the evidence of human papilloma virus (HPV) infection in esophageal squamous cell carcinomas (ESCC) and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants., Methods: Papilloma virus(PV) and HPV were determined by Ultrasensive S-P immunohistochemistry (IHC) and in situ hybridization (ISH)in esophageal carcinoma tissues (82 cases) and the normal mucosa (40 cases)., Results: IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV (16/18-E6) positive rate was 45.0%,36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV (16/18-E6) were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV (16/18) DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV (16/18) DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens (P<0.05). The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens (P>0.05)., Conclusion: HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital.HPV is closely related with esophageal squamous cell carcinoma. HPV infection may play an important role in esophageal squamous cell carcinoma.