DOCK8 interference alleviates Aß­induced damage of BV2 cells by inhibiting STAT3/NLRP3/NF­κB signaling.

Dementia is defined as memory loss and other cognitive decline and it severely influences daily life. Alzheimer's disease (AD) is the most common cause of dementia. Dedicator of cytokinesis 8 (DOCK8) is reported to be involved in neurological diseases. The present study focused on investigating the role that DOCK8 serves in AD and addressing its hidden regulatory mechanism. Initially, Aß1-42 (Aß) was applied for the administration of BV2 cells. Subsequently, the mRNA and protein expression levels of DOCK8 were evaluated utilizing reverse transcription-quantitative PCR (RT-qPCR) and western blotting. After the DOCK8 silencing, immunofluorescence staining (IF), ELISA, wound healing and Transwell assays were applied to assess ionized calcium binding adapter molecule-1 (IBA-1) expression, release of inflammatory factors, migration and invasion in Aß-induced BV2 cells. IF was used to evaluate cluster of differentiation (CD)11b expression. RT-qPCR and western blotting were to analyze the levels of M1 cell markers inducible nitric oxide synthase (iNOS) and CD86. The expression of STAT3/NLR family pyrin domain containing 3 (NLRP3)/NF-κB signaling-related proteins were determined by western blotting. Finally, the viability and apoptosis in hippocampal HT22 cells with DOCK8 depletion were estimated. Results revealed that Aß induction greatly stimulated the expression levels of IBA-1 and DOCK8. DOCK8 silencing suppressed Aß-induced inflammation, migration and invasion of BV2 cells. Additionally, DOCK8 deficiency conspicuously decreased the expression levels of CD11b, iNOS and CD86. The expression of phosphorylated (p-)STAT3, NLRP3, ASC, caspase1 and p-p65 was downregulated in Aß-induced BV2 cells after DOCK8 depletion. STAT3 activator Colivelin reversed the effects of DOCK8 knockdown on IBA-1 expression, inflammation, migration, invasion and M1 cell polarization. In addition, the viability and apoptosis in hippocampal HT22 cells stimulated by neuroinflammatory release of BV2 cells were repressed following DOCK8 deletion. Collectively, DOCK8 interference alleviated Aß-induced damage of BV2 cells by inhibiting STAT3/NLRP3/NF-κB signaling.

Ecological challenges in the economic recovery of resource-depleted cities in China.

The depletion of resource reserves will cause stagnation of socio-economic development in resource-based cities. The formation of new sources of economic growth in resource-depleted cities can profoundly change the structure of human activities and affect the environment. The Chinese government has established a list of resource-depleted cities in three batches since 2008 to support these cities in finding new sources of economic growth. The article analyzes the impact of the regeneration process of resource-based cities on ecosystem quality. The paper constructs an inter-city panel dataset covering 281 cities from 2003 to 2018. The article valued the habitat quality of Chinese cities. Habitat quality index and normalized vegetation index were used to measure the long-term and short-term ecological impacts of economic recovery in resource-based cities. Using a difference-in-difference technique, the results show that the central government's economic support for resource-based cities significantly improves the condition of urban ecosystems. However, the long-term ecological effects are still smaller than the short-term changes in ecosystems. The transmission path of support policies affecting the ecological quality of cities depends on the shift in industrial structure and economic scale at the provincial level. In addition, urban-rural differences, regional distribution, and resource endowment also significantly affect the ecological effects of supportive policies.

Methodological Study on the Establishment of HLA/HPA Gene Bank of Platelet Donors and Its Clinical Application.

The current study aimed at establishing a large-scale platelet donor database with known HPA and HLA genotypes in Ningbo, to provide matched platelets for the clinic and prevent the occurrence of ineffective immune platelet transfusion refractoriness (PTR). The platelet banks of clinical donor wtih HLA-A, HLA-B, HPA1, HPA2, HPA3, HPA4, HPA5, HPA6, HPA10, HPA15 and HPA21 genotyps were established. Meanwile, the platelet gene matching was performed on the donor. It was found that there were phenotype polymorphisms in 1000 donnors with HPA1, HPA2, HPA3, HPA4, HPA5, HPA6, HPA10, HPA15 and HPA21 genotyps, and allel polymorphism distribution in donnors with HPA1, HPA2, HPA3, HPA4, HPA5, HPA6, HPA15, HPA21 genotyps. The frequency of HPA10 was a gene, and not b gene, showing a single linear distribution. The HPA 2, HPA3, HPA15 system were the most polymorphic with three phenotypes: aa, ab, bb. In the HLA-A allele, the highest frequency is A*11:01 (24.25%). There were 13 alleles that were greater than 1%, such as A*24:02, A*02:01, A*33:03, and the accumulated frequency reached 96.20%. In the HLA-B allele, the highest gene frequency was B*40:01 (13.40%). There were 24 alleles that were greater than 1%, such as B*46: 01, B*58: 01, B*15: 01, and the accumulated frequency reached 91.60%. Platelet antibody cross matching was performed on 100 blood samples from patients with thrombocytopenia after multiple platelet transfusions. The number of consistent samples was 46 (46%). Twenty patients were transfused with platelet cross matching. Among them, 18 patients had obvious improvement in clinical symptoms and good hemostatic effect after transfusion, which was judged to be effective. Platelet donor HPA and HLA-A, B antigen genotyping database provided patients with individual appropriate platelets, and provided the effectiveness of immune platelet infusion ensuring effective platelet transfusion.

Experiment on Compressive Properties and Microscopic Analysis of Sea Sand Geopolymer-Based Recycled Concrete.

For marine and coastal engineering, construction resources have become scarce due to a limited local supply. Sea sand geopolymer-based recycled concrete (SSGRC) is an innovative cementitious material known for its eco-friendly benefits and corrosion resistance. This study explores the mechanical properties of SSGRC. The influences of the replacement rate of mineral slag, alkali activator concentrations, fine aggregate types, and curing ages on the compression strength of SSGRC were studied. The failure mechanism was analyzed using the failure patterns and compressive stress-strain curves. The results show that sea sand had a positive effect on geopolymer-based material. The SSGRC reached peak strength with an alkali activator concentration of 10 mol/L and a mineral slag replacement rate of 60%. The maximum stress and strain increased with an increasing curing age. The ratios of strength to the peak value were 55% and 85% after 1 day and 7 days, respectively. Using SEM, in the last hydration stage, the C-(A)-S-H gel was formed with a dense microstructure, and the geopolymer exhibited a favorable bonding performance. The constitutive models describing the complete stress-strain relationship under compression were developed.

Research on the innovation incentive effect and heterogeneity of the market-incentive environmental regulation on mineral resource enterprises.

Problems of ecological environment and resources have become an important factor restricting the high-quality development of China's economy. How to better integrate into the sustainable development model has become an important goal of macro-policy regulation in the transition period. Mining industry is a fundamental industry in China. Strengthening the incentive role of mining innovation is of great importance for ensuring China's energy security, reducing emissions and promoting economic growth. However, whether environmental regulation can induce technological innovation ability, that is, the existence of Porter effect, is still controversial. It is helpful to study the influence of the Porter hypothesis on mining enterprises for their sustainable development. Based on the data of listed companies in China from 2003 to 2018, and against the background of the SO2 emission trading pilot policy implemented in 2007, this paper studies the incentive effect of the market-incentive environmental regulation on the technological innovation ability of mineral resource enterprises, tests the existence of Porter effect, and discusses the heterogeneity. The results show that the market-incentive environmental regulation has a significant incentive effect on the innovation of mining enterprises, and there is significant Porter effect on mining enterprises. The robustness test confirms the correctness of this conclusion. At the same time, this paper also discusses the variation of the characteristics of heterogeneous enterprises, and finds that enterprises with utility model patents, no low-carbon behavior, and non-provincial cities and regions with high environmental regulation are more sensitive to the SO2 emission trading pilot policy. This paper verifies the incentive effect of the market-incentive environmental regulation on the innovation ability of mining enterprises, and provides a reference for the formulation of innovation incentive policies for mining enterprises in China.

Mining Eco-Efficiency Measurement and Driving Factors Identification Based on Meta-US-SBM in Guangxi Province, China.

The mining industry is one of the pillar industries of Guangxi's economic and social development. The output value of mining and related industries accounts for 27% of the whole district's total industrial output value. Therefore, the mining eco-efficiency measurement in Guangxi can be of great significance for the sustainable development of Guangxi's mining industry. This study adopted Meta-US-SBM to measure the mining eco-efficiency in Guangxi from 2008 to 2018, including economic efficiency, resource efficiency, and environmental efficiency. It used the standard deviation ellipse model to simulate the migration trend of four efficiencies in Guangxi and used GeoDetector and Tobit models to explore the internal and external factors that affect the mining eco-efficiency. The four efficiencies in Guangxi show large temporal and spatial heterogeneity, and the internal and external factors that affect the mining eco-efficiency are different. The following conclusions can be drawn. (1) Environmental efficiency and mining eco-efficiency are improving, while economic efficiency and resource efficiency are deteriorating. Cities bordering other provinces have a significantly better mining eco-efficiency than non-bordering cities. (2) The development center in Guangxi has migrated to the Beibu Gulf Economic Zone. (3) Natural resources index and mining economic scale have a great impact on the mining eco-efficiency, and with the increase of the mining economic scale, the mining eco-efficiency showed a typical "U-shaped" curve. Finally, this study put forward corresponding policy recommendations to improve the mining eco-efficiency in Guangxi from four aspects: opening-up, technological progress, regional coordination, and government control.

[Molecular genetic analysis of two individuals with weak D variant of the Rh blood type].

OBJECTIVE: To explore the molecular basis of two individuals with weak D variant of the Rh blood type. METHODS: Routine serological testing was carried out to detect the D, C, c, E and e antigens of the Rh blood group. The D antigen was further detected with an indirect antiglobulin test. The presence of Rhesus box was detected by PCR to determine the homozygosity of the RHD gene. RESULTS: Both samples were determined as weak D phenotype by the indirect antiglobulin test. DNA sequencing revealed that case 1 harbored a heterozygous 208C>T variant in exon 2 and a heterozygous 1227G>A variant in exon 9; while case 2 harbored homozygous 779A>G variants of exon 5 of the RHD gene. Case 1 was determined as RHD+/RHD+, while case 2 was determined as RHD+/RHD-. The two samples were respectively named as weak D type 122 and weak D type 149 based on the rules of Rhesus Base Nomenclature. CONCLUSION: D negative blood donors should subject to indirect antiglobulin testing and molecular analysis for safer transfusion.

Relationship between energy consumption, economic growth and environmental pollution in China.

In recent days, many emerging nations facing severe environmental pollution problems. In order to overcome the environmental problems, many new methods and strategies have been built and some advance sources of energies were also utilized in order to overcome such issues but by using such sources, many challenges were faced. In order to find best possible solutions of such issues, this paper was aimed to minimize the gap of research by examining the effect on economic development of energy expenditure and environmental pollution and by means of finding the casual relationship between them because it has been observed that with development of economy, environmental issues always increase. Effects of both traditional and modern energies was analyzed in this research. Several explanatory variables will be used: Renewable energy consumption, CO2 emission, economic GDP. Environmental pollution will be taken as the mediating factor that influence this association between energy utilization as well as economic development. Present study was based on the economy of China. ARDL regression model was applied in this research to increase the time series econometrics when non-stationary value demonstrated the co-integration and it is also effective for both stationary and non-stationary time series. At the end, some advanced methods of production were discussed that can be used in this era of industry 4.0. By proper implementation of such processes, many economic and environmental benefits can be achieved.

The effectiveness of eco-compensation in environmental protection -A hybrid of the government and market.

The Payments for Ecosystem Services (PES) program has provided policy innovation for global environmental affairs. China, the largest developing country in the world, is also faced with serious environmental problems. China developed a unique environmental policy - ecological compensation (Eco-compensation), which combined the flexibility of the PES mechanism with efficient government management. The paper studies the efficiency of eco-compensation policy in a large-scale region and the stability of policy in a long-time. We use the counterfactual method - Synthetic Control Method (SCM) to analyze the eco-compensation policy. Zhejiang province, China, which is the first province to implement Eco-compensation policy, chose as study case. We run several robustness checks to discuss the influence of other factors, including economy, politics and geology. The result shows that the eco-compensation policy improve the region's environment significantly. And it never has negative impact for the economy of Zhejiang. We discuss some experiences and challenges of this policy. The paper thinks that localization and the hybrid of government and market could provide successful experience for this policy.

Strategic interactions in environmental regulation enforcement: evidence from Chinese cities.

Environmental regulation policy is the main means of pollution control and emission reduction and plays an irreplaceable role in environmental governance. However, due to the competitive behavior of economic development, the local government cannot effectively use the efficiency of environmental regulation to reduce the emission of environmental pollution. Taking 284 prefecture-level cities in China from 2005 to 2016 as samples, this paper studies the strategic interaction of environmental regulation enforcement by local governments under different circumstances and its impact on environmental pollution, so as to provide reference for national overall environmental governance planning. Through the research, it is found that the strategic interaction of environmental regulation enforcement among Chinese cities is characterized by the race-to-the-top. And the strategic interaction of environmental regulation enforcement among cities of the same economic level has the strongest impact. Besides, the impact of environmental regulation on environmental pollution has different intensity in different scenarios, showing a non-positive correlation. Most importantly, the Pollution Paradise exists in some cities under special circumstances.

Asymmetric impact of energy consumption and economic growth on ecological footprint: Using asymmetric and nonlinear approach.

The main objective of this article is to examine the impacts of energy consumption and economic growth on environmental quality in Pakistan. We use the ecological footprint (environmental quality) as a target variable, the control variables of gross domestic products are a proxy of economic growth, and energy consumption and gross fixed capital formation are proxies of capital from 1971 to 2014. For this purpose, a unit root test with break dates is employed for a stationary check, and a BDS test is used for nonlinearity. The nonlinear autoregressive distributed lag approach is employed to assess the asymmetric co-integration among the variables. These results confirm the asymmetric co-integration among the variables. The asymmetric causality technique is also applied to scrutinize the causal link between the variables. The asymmetric feedback effect is observed between positive shocks to environmental quality and energy consumption, and symmetrically, environmental quality causes energy consumption. By contrast, the neutral effect is observed among environmental quality, economic growth, and capital. Based on these findings, current energy portfolios should be diversified by either enhancing or incorporating renewable energy technologies, and this is indispensable to support the existing successful strides of environmental policies. Thus, policymakers must buttress their commitments to reduce emissions by sustaining and decarbonizing the trajectory of economic growth.

[A case with a novel weak D type].

OBJECTIVE: To report on a novel weak D type identified in a Chinese individual. METHODS: Peripheral blood sample was collected for a voluntary blood donor with weakened expression of D antigen. Routine serological testing was carried out to determine the D, C, c, E and e antigens of the Rh blood group. A D-screening kit was used to analyze the RhD epitopes. The 10 exons and flanking intronic regions of the RHD gene were sequenced. The zygosity of RHD was determined with a sequence-specific primer PCR method. RESULTS: A novel RHD allele, RHD (1022T>A), was found in the subject with a weak D phenotype. Serological testing of the RhD epitopes has coined with the weak D phenotype. CONCLUSION: A novel weak D allele has been identified in Chinese population.

The impact of environmental regulation on environmental pollution in China: an empirical study based on the synergistic effect of industrial agglomeration.

In recent years, as environmental degradation has become more and more serious, the Chinese government has formulated a series of environmental policies and regulations aimed at improving environmental quality. Does environmental regulation significantly inhibit environmental pollution? Environmental regulation will not only directly affect environmental pollution but also have an indirect impact on environmental pollution. This paper uses Bayesian posterior probability, the optimal model structure selection method, based on join 112 kinds of spatial econometric model structure, and the panel data of 30 provinces in China from 2003 to 2016 to study the effects of environmental regulation on environmental pollution base on the industrial agglomeration mechanism of synergy effect. The research covers the national level and four regions, including the eastern, central, western, and northeastern regions of China. The research shows that: (1) environmental regulation at the national level and in the eastern, central and northeastern regions can significantly curb environmental pollution, but the environmental pollution in the western region shows a significant trend of enhancement. (2) Increased industrial agglomeration across China has significantly worsened environmental pollution. (3) Environmental regulation and industrial agglomeration form a significant synergy effect, which has a significant positive impact on environmental pollution in regions other than northeast China, and a significant negative impact on environmental pollution intensity in northeast China.

[Identification of a novel FUT1 allele of para-Bombay phenotype].

OBJECTIVE: To explore the molecular basis for an individual with para-Bombay phenotype of the H blood group. METHODS: Intron 5 to 3'-UTR of the ABO gene and exon 4 of the FUT1 gene were amplified with PCR and subjected to direct sequencing. Mutations of the FUT1 gene were identified by TOPO cloning sequencing. RESULTS: Direct sequencing showed that her ABO genotype was B101/O01. TOPO cloning sequencing found that this individual had three mutations of the FUT1 gene, including an heterozygous AG deletion (CAGAGAG→CAGAG) at position 547 to 552, and two C→T mutations at positions 35 (C35T) and 293 (C293T) on the other homologous chromosome. The two alleles comprised a new recombination of mutations c.35T>C and c.293C>T, and the sequence has been submitted to NCBI (No. MG597611). CONCLUSION: A novel combination of FUT1 alleles with c.35 C>T and c.293C>T has been identified in an individual with para-Bombay phenotype.

Has China's Pilot Emissions Trading Scheme Influenced the Carbon Intensity of Output?

China launched the pilot construction of the carbon emission trading scheme (ETS) in 2011. The pilots have been running for many years. Does ETS significantly restrain the increase of carbon emission intensity? Based on China's panel data for provinces and industries, this paper uses the policy assessment method to evaluate the inhibition by ETS of carbon emission intensity. The assessment scope includes six provincial pilots and pilot industries covered by ETS. The results show that ETS has significant suppression of carbon emission intensity only in Beijing and Guangdong. There is no significant impact on the carbon emission intensity of Tianjin, Shanghai, Chongqing, and Hubei. Through the carbon emission intensity inhibition analysis of the industries covered by ETS from Beijing and Chongqing, the results of the production and supply of electric power, steam and hot water, petroleum processing and coking in Beijing have a significant impact on the ETS. Only the smelting and pressing of ferrous metals in Chongqing has a significant impact on the ETS.

Isosteviol Protects Free Fatty Acid- and High Fat Diet-Induced Hepatic Injury via Modulating PKC-ß/p66Shc/ROS and Endoplasmic Reticulum Stress Pathways.

Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases. However, there are no approved pharmacotherapies for the treatment of NAFLD other than managing life style and controlling diets. Extensive studies have demonstrated that multiple mechanisms are involved in free fatty acid (FFA)- and high fat diet (HFD)-induced hepatic injury, including mitochondrial dysfunction, activation of oxidative stress and endoplasmic reticulum (ER) stress, and lysosome dysfunction. A previous study reported that Isosteviol (ISV), a derivative of stevioside, prevents HFD-induced hepatic injury. However, the underlying mechanisms remain unclear. Results: In this study, we examined the potential cellular/molecular mechanisms underlying ISV-mediated protective effect against FFA-/HFD-induced hepatic lipotoxicity by using both in vitro primary rat hepatocytes and the in vivo rat NAFLD model. The results indicated that ISV inhibits FFA-/HFD-induced hepatic injury via reducing oxidative and ER stress. Specifically, ISV inhibited the expression, activation, and mitochondrial translocation of Src-homology-2-domain-containing transforming protein 1 (p66Shc), an adapter protein that mediates oxidative stress-induced injury and is a substrate of protein kinase C-ß (PKC-ß), via inhibition of PKC-ß activity. However, ISV had no effect on the expression and activity of peptidyl-prolyl cis-trans isomerase and serine/threonine protein phosphatase 2A, isomerase and phosphorylase of p66Shc. In addition, ISV also inhibited FFA-induced ER stress and decreased ER-mitochondrial interaction. Innovation and Conclusion: We first identified that ISV prevents FFA-/HFD-induced hepatic injury through modulating PKC-ß/p66Shc/oxidative and ER stress pathways. ISV represents a promising therapeutic agent for NAFLD in the future. Antioxid. Redox Signal. 30, 1949-1968.

[Identification of a novel Ax allele of the ABO blood group].

OBJECTIVE: To explore the molecular basis for an individual with Ax28 phenotype of the ABO subtype. METHODS: The ABO group antigens on red blood cells of the proband were identified by monoclonal antibodies. The ABO antibody in serum was detected by standard A, B, O cells. Exons 1 to 7 of the ABO gene were respectively amplified by PCR and directly sequenced. Amplicons for exons 5 to 7 were also sequenced after cloning. RESULTS: Weakened A antigen was detected on red blood cells from the proband. Both anti-A and anti-B antibodies were detected in the serum. Heterozygous 261G/del was detected in exon 6, while heterozygous 467C/T and 830T/C were detected in exon 7 by direct DNA sequencing. After cloning and sequencing, two alleles (O01 and Ax28) were obtained. Compared with A102, the sequence of Ax28 contained one nucleotide changes (T to C) at position 830, which resulted in amino acid change (Val to Ala) at position 277. CONCLUSION: The novel mutation c.830T>C of the galactosaminyltransferase gene may give rise to the Ax28 phenotype.

Effect of Nitric Oxide Donor on Metabolism of Apheresis Platelets.

The aim of this study is to investigate the effects of a nitric oxide (NO) donor S-nitrosoglutathione (GSNO) on the metabolism and improvement of preservation quality in apheresis platelets. A GSNO solution with a certain concentration was added into fresh apheresis platelets, and the parameters associated with platelet morphology, metabolism and function were temporally monitored for 7 days. The results showed that the NO level in GSNO group were remarkably higher than those in the control group during the whole storage stage. No significant morphology or function difference was observed between the control and GSNO groups such as Platelet count, platelet distribution width, mean platelet volume and mitochondrial metabolic activity. But in metabolism there are something differences from morphology data: pCO2, pO2, cHCO3- were also found to have no clear difference between the control and GSNO groups; the lactic acid content, sugar consumption and Lactate dehydrogenase activity in the GSNO group were lower than that in the control group at some time point; and pH values in the GSNO group were higher than the control group. Our study discovered that the NO donor GSNO can reduce the metabolism and maintain the cellular characteristics of platelets in vitro during the platelet storage period.