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The electrochemical nitrate reduction reaction (NO3RR) is considered a sustainable technology to convert the nitrate pollutants to ammonia. However, developing highly efficient electrocatalysts is necessary and challenging given the slow kinetics of the NO3RR with an eight-electron transfer process. Here, a Cu1.5Mn1.5O4 (CMO)/CeO2 heterostructure with rich interfaces is designed and fabricated through an electrospinning and postprocessing technique. Benefiting from the strong coupling between CMO and CeO2, the optimized CMO/CeO2-2 catalyst presents excellent NO3RR performance, with NH3 Faraday efficiency (FE) up to 93.07 ± 1.45% at -0.481 V vs reversible hydrogen electrode (RHE) and NH3 yield rate up to 48.06 ± 1.32 mg cm-2 h-1 at -0.681 V vs RHE. Theoretical calculations demonstrate that the integration of CeO2 with CMO modulates the adsorption/desorption process of the reactants and intermediates, showing a reduced energy barrier in the rate determination step of NO* to N* and achieving an outstanding NO3RR performance.
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Rational designing electrocatalysts is of great significance for realizing high-efficiency H2 production in the water splitting process. Generally, reducing the usage of precious metals and developing low-potential nucleophiles oxidation reaction to replace anodic oxygen evolution reaction (OER) are efficient strategies to promote H2 generation. Here, NiS-coated nickel-carbon nanofibers (NiS@Ni-CNFs) are prepared for low-content Pt deposition (Pt-NiS@Ni-CNFs) to attain the alkaline HER catalyst. Due to the reconfiguration of NiS phase and synergistic effect between Pt and nickel sulfides, the Pt-NiS@Ni-CNFs catalyst shows a high mass activity of 2.74-fold of benchmark Pt/C sample. In addition, the NiS@Ni-CNFs catalyst performs a superior urea oxidation reaction (UOR) activity with the potential of 1.366 V versus reversible hydrogen electrode (RHE) at 10 mA cm-2 , which demonstrates the great potential in the replacement of OER. Thus, a urea-assisted water splitting electrolyzer of Pt-NiS@Ni-CNFs (cathode)||NiS@Ni-CNFs (anode) is constructed to exhibit small voltages of 1.44 and 1.65 V to reach 10 and 100 mA cm-2 , which is much lower than its overall water splitting process, and presents a 6.5-fold hydrogen production rate enhancement. This work offers great opportunity to design new catalysts toward urea-assisted water splitting with significantly promoted hydrogen productivity and reduced energy consumption.
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Nowadays, highly active and stable alkaline bifunctional electrocatalysts toward water electrolysis that can work at high current density (≥1000 mA cm-2) are urgently needed. Herein, Mn-doped RuO2 (MnxRu1-xO2) nanofibers (NFs) are constructed to achieve this object, presenting wonderful hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performances with the overpotentials of only 269 and 461 mV at 1 A cm-2 in 1 m KOH solution, and remarkably stability under industrial demand with 1 A cm-2, significantly better than the benchmark Pt/C and commercial RuO2 electrocatalysts, respectively. More importantly, the assembled Mn0.05Ru0.95O2 NFs||Mn0.05Ru0.95O2 NFs electrolyzer toward overall water splitting reaches the current density of 10 mA cm-2 with a cell voltage of 1.52 V and also delivers an outstanding stability over 150 h of continuous operation, far surpassing commercial Pt/C||commercial RuO2, RuO2 NFs||RuO2 NFs and most previously reported exceptional electrolyzers. Theoretical calculations indicate that Mn-doping into RuO2 can significantly optimize the electronic structure and weaken the strength of OâH bond to achieve the near-zero hydrogen adsorption free energy (ΔGH*) value for HER, and can also effectively weaken the adsorption strength of intermediate O* at the relevant sites, achieving the higher OER catalytic activity, since the overlapping center of p-d orbitals is closer to the Fermi level.
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Klebsiella pneumoniae, especially hypervirulent K. pneumoniae (hvKP), is a common opportunistic pathogen that often causes hospital- and community-acquired infections. Capsular polysaccharide (CPS) is an important virulence factor of K. pneumoniae. Some phages encode depolymerases that can recognize and degrade bacterial polysaccharides. In this study, the lytic bacteriophage vB_KpnP_ZK1 (abbreviated as ZK1) was isolated using serotype K1 hvKP as the host. Although amino acid sequence BLAST analysis indicated that the tail fiber protein Depo16 of phage ZK1 showed no significant similarity to any reported phage depolymerases, it displayed enzymatic activities that are characteristic of phage depolymerases. After expression and purification, Depo16 could efficiently remove the capsular polysaccharide layer that surrounds the surface of serotype K1 K. pneumoniae. Although no bactericidal activity was detected, Depo16 makes serotype K1 K. pneumoniae sensitive to peritoneal macrophages (PMs). In addition, in a mouse bacteremia model of serotype K1 K. pneumoniae, 25 µg of Depo16 was effective in significantly prolonging survival. Depo16 treatment can reduce the bacterial load in blood and major tissues and alleviate tissue damage in mice. This indicates that the putative depolymerase Depo16 is a potential antibacterial agent against serotype K1 K. pneumoniae infections.IMPORTANCEKlebsiella pneumoniae often causes hospital-acquired infections and community-acquired infections. Capsular polysaccharide (CPS) is one of the crucial virulence factors of K. pneumoniae. K1 and K2 capsular-type K. pneumoniae strains are the most prevalent serotypes of hypervirulent K. pneumoniae (hvKP). In this study, a novel K. pneumoniae phage named vB_KpnP_ZK1 was isolated, and its putative depolymerase Depo16 showed low homology with other reported phage depolymerases. Depo16 can specifically degrade the K. pneumoniae K1 capsule making this serotype sensitive to peritoneal macrophages. More importantly, Depo16 showed a significant therapeutic effect in a mouse bacteremia model caused by serotype K1 K. pneumoniae. Thus, Depo16 is a potential antibacterial agent to combat serotype K1 K. pneumoniae infections.
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Bacteriemia , Bacteriófagos , Infecções Comunitárias Adquiridas , Infecções por Klebsiella , Animais , Camundongos , Klebsiella pneumoniae , Bacteriófagos/genética , Infecções por Klebsiella/terapia , Infecções por Klebsiella/microbiologia , Fatores de Virulência/metabolismo , Polissacarídeos Bacterianos , AntibacterianosRESUMO
The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4ï¼GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.
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Ácidos Alcanossulfônicos , Autofagia , Cálcio , Coenzima A Ligases , Ferroptose , Fluorocarbonos , Hepatopatia Gordurosa não Alcoólica , Ferroptose/efeitos dos fármacos , Fluorocarbonos/toxicidade , Animais , Ácidos Alcanossulfônicos/toxicidade , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Autofagia/efeitos dos fármacos , Coenzima A Ligases/metabolismo , Humanos , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Linhagem Celular , Hepatócitos/efeitos dos fármacosRESUMO
In the context of the goal of "carbon neutrality", an economic development model that achieves emission reduction goals and ensures stable economic growth is currently being advocated by China. Based on provincial panel data in China from 2005 to 2016, we analyse the impact of economic growth target (EGT) constraints on environmental pollution using a spatial econometric method. The results indicate that EGT constraints significantly exacerbate environmental pollution in local regions and adjacent areas. Local governments are motivated to achieve economic growth goals at the expense of the ecological environment. The positive effects are attributed to a reduction in environmental regulation (ER), industrial structure upgrading and technological innovation and an increase in foreign direct investment (FDI). Moreover, environmental decentralization (ED) plays a positive regulatory role and can weaken the adverse influences of EGT constraints on environmental pollution. Interestingly, the nonlinear impact of EGT constraints on environmental pollution relies on different types of ED. Environmental administration decentralization (EDA) and environmental supervision decentralization (EDS) can reduce the positive effect of EGT constraints on environmental pollution, while an improvement in environmental monitoring decentralization (EDM) can increase the promoting influences of the constraints of economic growth goals on environmental pollution. The above conclusions still hold under a series of robustness tests. Based on the above findings, we suggest that local governments set scientific growth targets, establish scientific assessment indicators for officials, and optimize the ED management institution.
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Desenvolvimento Econômico , Poluição Ambiental , Poluição Ambiental/análise , Invenções , Investimentos em Saúde , China , PolíticaRESUMO
The digital economy has demonstrated strong resilience and great potential, under the interwoven influence of the global pandemic and severe environmental concerns across the world. Therefore, there is a need to focus on the value of green economic growth in the digital economy. This paper constructs an evaluation index system and adopts the SEEA (System of Environmental and Economic Accounting) method to measure the digitalization level (Digi) and green economy growth level (GEG) of China. The internal mechanism and linear relationship between digitalization and green economy growth are examined based on the panel data from 2013 to 2019. Moreover, this study explores the spatial spillover effect. The major study findings are as follows: (1) Digitalization and green economy growth represent a steady growth trend, and the former as a whole significantly promotes the latter, with a marginal effect of 1.648. (2) The mechanism analysis indicates the intermediary effects' size of three crucial intermediaries: green technology innovation > advanced industrial structure > the rationalization of industrial structure. (3) Both the "local effect" (0.556; 0.574) and "neighboring effect" (1.382; 1.415) of digitalization on green economy growth are positive under the two weight matrices and display "simultaneous resonance" characteristics based on the spatial perspective. (4) There exists obvious regional spatial heterogeneity and resource endowment heterogeneity. Finally, this study put forward corresponding policy implications, such as construction of new digital infrastructures and guiding green-energy consumption.
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Desenvolvimento Econômico , Indústrias , Invenções , ChinaRESUMO
The design of void-confined tubular nanostructures has aroused significant interest for catalytic applications because of their distinct microenvironment to modulate the reaction kinetics. Herein, we propose a facile wrapping-pyrolysis strategy to confine Fe0 nanoparticles (Fe NPs) inside N-doped carbon nanotubes (Fe@NC NTs) derived from Fe2O3@polypyrrole (PPy) core-sheath nanofibers (NFs). The resultant Fe@NC NTs can act as efficient enzyme mimics and exhibit a significantly higher peroxidase (POD)-like catalytic activity than unconfined Fe NPs and bare NC NTs. Kinetic experiments demonstrate that the optimized void structure benefits the affinity with the POD substrates and achieves excellent catalytic efficiency. The mechanism study reveals that the generation of â¢OH from H2O2 endows Fe@NC NTs with excellent POD-like performance. Furthermore, we develop a total antioxidant capacity (TAC) sensing platform on account of this efficient POD-like system, expanding their applications in the field of food safety and human healthcare.
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Nanotubos de Carbono , Polímeros , Antioxidantes , Bioensaio , Catálise , Humanos , Peróxido de Hidrogênio/química , Nanotecnologia , Polímeros/química , Pirróis/químicaRESUMO
Major depressive disorder is a highly debilitating psychiatric disorder involving the dysfunction of different cell types in the brain. Microglia are the predominant resident immune cells in the brain and exhibit a critical role in depression. Recent studies have suggested that depression can be regarded as a microglial disease. Microglia regulate inflammation, synaptic plasticity, and the formation of neural networks, all of which affect depression. In this review, we highlighted the role of microglia in the pathology of depression. First, we described microglial activation in animal models and clinically depressed patients. Second, we emphasized the possible mechanisms by which microglia recognize depression-associated stress and regulate conditions. Third, we described how antidepressants (clinical medicines and natural products) affect microglial activation. Thus, this review aimed to objectively analyze the role of microglia in depression and focus on potential antidepressants. These data suggested that regulation of microglial actions might be a novel therapeutic strategy to counteract the adverse effects of devastating mental disorders.
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Transtorno Depressivo Maior , Microglia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Humanos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Plasticidade Neuronal/fisiologiaRESUMO
Excitatory toxicity is still a hot topic in the study of ischemic stroke, and related research has focused mainly on neurons. Adenosine is an important neuromodulator that is known as a "biosignature" in the central nervous system (CNS). The protective effect of exogenous adenosine on neurons has been confirmed, but its mechanism remains elusive. In this study, astrocytes were pretreated with adenosine, and the effects of an A2a receptor (A2aR) inhibitor (SCH58261) and A2b receptor (A2bR) inhibitor (PSB1115) on excitatory glutamate were investigated. An oxygen glucose deprivation/reoxygenation (OGD/R) and glutamate model was generated in vitro. Post-model assessment included expression levels of glutamate transporters (glt-1), gap junction protein (Cx43) and glutamate receptor (AMPAR), Na+-K+-ATPase activity, and diffusion distance of dyes. Glutamate and glutamine contents were determined at different time points. The results showed that (1) adenosine could improve the function of Na+-K+-ATPase, upregulate the expression of glt-1, and enhance the synthesis of glutamine in astrocytes. This effect was associated with A2aR activation but not with A2bR activation. (2) Adenosine could inhibit the expression of gap junction protein (Cx43) and reduce glutamate diffusion. Inhibition of A2aR attenuated adenosine inhibition of gap junction intercellular communication (GJIC) in the OGD/R model, while it enhanced adenosine inhibition of GJIC in the glutamate model, depending on the glutamate concentration. (3) Adenosine could cause AMPAR gradually entered the nucleus from the cytoplasm, thereby reducing the expression of AMPAR on the cell membrane. Taken together, the results indicate that adenosine plays a role of anti-excitatory toxicity effect in protection against neuronal death and the functional recovery of ischemic stroke mainly by targeting astrocytes, which are closely related to A2aR. The present study provided a scientific basis for adenosine prevention and ischemic stroke treatment, thereby providing a new approach for alleviating ischemic stroke.
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Adenosina/farmacologia , Astrócitos/patologia , Aminoácidos Excitatórios/toxicidade , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Transporte Biológico/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Células Cultivadas , Conexina 43/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Corantes Fluorescentes/metabolismo , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Glucose/deficiência , Ácido Glutâmico/metabolismo , Modelos Biológicos , Oxigênio , Ratos Sprague-Dawley , Receptores de AMPA/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Due to global warming and increasingly severe resource and environmental constraints, the role of renewable energy in reducing pollutant emissions and mitigating environmental degradation has gradually attracted the attention of all countries. This study examines the relationship between government corruption, market segmentation, and renewable energy technology innovation. The regression results show that government corruption can increase the degree of market segmentation, and both government corruption and market segmentation can significantly reduce regional renewable energy technology innovation. Further analysis shows that the improvement in market segmentation can lead to a negative moderating effect of corruption on renewable energy technology innovation. In addition, corruption and market segmentation have complementary effects on the impact of renewable energy technology innovation. The improvement of corruption level can increase the negative influences of market segmentation on renewable energy technology innovation. Similarly, the higher degree of market segmentation can increase the restraining effect of corruption on renewable energy technology innovation. Therefore, this study provides a valuable reference for all countries to accelerate the construction of regional market integration, break through interprovincial barriers, and improve renewable energy technology innovation.
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Dióxido de Carbono , Desenvolvimento Econômico , Dióxido de Carbono/análise , China , Governo , Invenções , Energia RenovávelRESUMO
Gentiana species including G. crassicaulis, G. macrophylla, G. dahurica, and G. straminea are used in traditional Chinese medicine as "Qinjiao" for the treatment of rheumatism, hepatitis, and pain. Four antifungal bisphosphocholines [irlbacholine (2) and three new analogues, gentianalines A-C (1, 3, and 4)] were identified from G. crassicaulis by a bioassay-guided fractionation and structure elucidation approach. Subsequent chemical analysis of 56 "Qinjiao" samples (45 from G. crassicaulis, five from G. macrophylla, three from G. dahurica, and three from G. straminea) showed that bisphosphocholines were present in all four Gentiana species, with irlbacholine as the major compound ranging from 2.0 to 6.2 mg per gram of dried material. Irlbacholine exhibited potent in vitro antifungal activity against Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans, and Candida glabrata with minimum inhibitory concentration (MIC) values of 0.63, 1.25, 10.0, and 5.0 µg/mL, respectively. Identification of the bisphosphocholines, a rare class of antifungal natural products, in these medicinal plants provides scientific evidence to complement their medicinal use. The bisphosphocholines carrying a long aliphatic chain possess amphiphilic molecule-like properties with a tendency of retention in both normal and reversed-phase silica gel column chromatography and thereby may be neglected in natural products discovery. This report may stimulate interest in this class of compounds, which warrant the further study of other biological activities as well.
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Antifúngicos/química , Antifúngicos/farmacologia , Gentiana/química , Fosforilcolina/química , Fosforilcolina/farmacologia , Bioensaio , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Plantas Medicinais , Relação Estrutura-AtividadeRESUMO
The endocannabinoid system (ECS) has received extensive attention for its neuroprotective effect on the brain. This system comprises endocannabinoids, endocannabinoid receptors, and the corresponding ligands and proteins. The molecular players involved in their regulation and metabolism are potential therapeutic targets for neuropsychiatric diseases including anxiety, depression and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The inhibitors of two endocannabinoid hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), have the capacity to increase the level of endocannabinoids indirectly, causing fewer side effects than those associated with direct supplementation of cannabinoids. Their antidepressant and anxiolytic mechanisms are considered to modulate the hypothalamic-pituitary-adrenal axis and regulate synaptic and neural plasticity. In terms of AD/PD, treatment with FAAH/MAGL inhibitors leads to reduction in amyloid ß-protein deposition and inhibition of the death of dopamine neurons, which are commonly accepted to underlie the pathogenesis of AD and PD, respectively. Inflammation as the cause of depression/anxiety and PD/AD is also the target of FAAH/MAGL inhibitors. In this review, we summarize the application and involvement of FAAH/MAGL inhibitors in related neurological diseases. Focus on the latest research progress using FAAH/MAGL inhibitors is expected to facilitate the development of novel approaches with therapeutic potential.
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Doença de Alzheimer/tratamento farmacológico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Amidoidrolases/antagonistas & inibidores , Animais , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Monoacilglicerol Lipases/antagonistas & inibidoresRESUMO
In recent years, an increasing number of Listeria monocytogenes strains with resistance to quaternary ammonium compounds (QACs) have been reported. However, the genetic basis for QACs resistance in L. monocytogenes remains poorly understood. In the present study, we have characterized the operon lmo0852/lmo0853/lmo0854 (designated sugR/sugE1/sugE2) that contributes to QACs' resistance in L. monocytogenes EGD-e. We constructed the gene deletion mutants and the complemented strains, determined minimum inhibitory concentrations (MICs) of these strains against antimicrobial agents, assessed the transcription levels of target genes by RT-qPCR, and measured the promoter activity by using ß-galactosidase assays. We also investigated the interaction between the promoter DNA and the putative regulatory protein by electrophoretic mobility shift assay (EMSA). The sug operon consists of a putative TetR family regulator encoded by sugR and two small multidrug resistance (SMR) efflux pumps encoded by sugE1 and sugE2. Our results showed that either SugE1 or SugE2 is sufficient for QACs' resistance, indicating their function overlapping in QACs' resistance. Interestingly, lacking one sugE gene could lead to a significant increase in transcription of the other sugE gene in the presence of benzalkonium chloride (BC). Additionally, SugR negatively regulates the transcription of the sug locus by binding to the operon promoter. Given that QACs are commonly used in food industry, the findings from this study will help us to have a better understanding of the adaptations of L. monocytogenes to this type of disinfectant. Key points â¢Either SugE1 or SugE2 was sufficient for QACs resistance. â¢The functions of two sug genes overlap and compensate each other in QACs resistance. â¢SugR is the transcriptional suppressor of sugE1 and sugE2. â¢SugR regulates the sug locus by binding to the operon promoter.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/genética , Óperon , Compostos de Amônio Quaternário/farmacologia , Desinfetantes/farmacologia , Microbiologia de Alimentos , Proteínas de Membrana/genética , Testes de Sensibilidade MicrobianaRESUMO
Following the "Belt and Road" (B&R) initiative, China has significantly increased its outward direct investment (ODI). Although these investments help to boost these countries' productivity, their impacts on the environment are still controversial and deserve careful investigation. This study for the first time examines whether China's ODI has improved the green total factor productivity (GTFP), a comprehensive index for environmental quality and productivity. Moreover, a new data set composed of ICRG, World Bank WDI, Heritage Foundation, and Wind databases is used to match the panel data of 46 B&R countries for the period of 2003-2016. A newly developed dynamic threshold panel model with GMM characteristics is utilized to explore the possible nonlinear relationship with full consideration of heterogeneity. The empirical results indicate that there is no pollution shelter effect on China's ODI. With the increase in China's ODI, the GTFP of the B&R countries has been significantly improved. Additionally, China's ODI has a greater role in promoting GTFP in B&R countries with higher institutional quality. The positive effects of China's ODI on the GTFP of B&R countries depend on the institutional qualities of the countries, and the enhancement effect becomes greater when the countries have better institutions. There is also evidence that China's ODI significantly promoted the GTFP of countries in the East Asia and Pacific region, South Asia, Central Asia and Europe, while China's ODI did not significantly promote the GTFP of countries in the Middle East and North Africa.
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África do Norte , Ásia , China , Europa (Continente) , Oriente MédioRESUMO
The green alga Klebsormidium flaccidum var. zivo is a rich source of proteins, polyphenols, and bioactive small-molecule compounds. An approach involving chromatographic fractionation, anti-inflammatory activity testing, ultrahigh performance liquid chromatography-mass spectrometry profiling, chemometric analysis, and subsequent MS-oriented isolation was employed to rapidly identify its small-molecule anti-inflammatory compounds including hydroxylated fatty acids, chlorophyll-derived pheophorbides, carotenoids, and glycoglycerolipids. Pheophorbide a, which decreased intracellular nitric oxide production by inhibiting inducible nitric oxide synthase, was the most potent compound identified with an IC50 value of 0.24 µM in lipopolysaccharides-induced macrophages. It also inhibited nuclear factor kappaB activation with an IC50 value of 32.1 µM in phorbol 12-myristate 13-acetate-induced chondrocytes. Compared to conventional bioassay-guided fractionation, this approach is more efficient for rapid identification of multiple chemical classes of bioactive compounds from a complex natural product mixture.
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Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Clorófitas/química , Modelos Químicos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Camundongos , Células RAW 264.7 , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
In Listeria monocytogenes, it has been proposed that the VirSR two-component signal transduction systems (TCSs) and two ATP-binding cassette (ABC) transporters, VirAB and AnrAB, constitute a complex TCS/ABC transporter system which has been recognized as a unique resistance mode. The role of the putative VirAB-VirSR-AnrAB system in antimicrobial resistance and the respective contributions of the members of the system to resistance were investigated in this study. We constructed gene deletion mutants of L. monocytogenes EGD-e and complemented strains of the mutants and determined MICs of antimicrobial agents against these strains against using the agar dilution method. We assessed the relative expression levels of target genes by reverse transcription-quantitative PCR (RT-qPCR) and measured promoter activity levels by ß-galactosidase assays. Our results showed that the VirAB-VirSR-AnrAB system mediates not only nisin and bacitracin resistance but also resistance to cephalosporins, ethidium bromide (EtBr), and benzalkonium chloride (BC). In this system, two ABC transporters, VirAB and AnrAB, play distinct roles in cefotaxime resistance: the former is responsible only for antimicrobial sensing and signaling by VirSR, while the latter contributes to transportation of antimicrobials. Notably, VirAB itself, rather than the VirAB-VirSR-AnrAB system as a whole, contributes to kanamycin and tetracycline resistance. On the basis of the results obtained from this study, we speculate that VirAB acts as a sensor for VirSR in response to cephalosporins, bacitracin, nisin, EtBr, and BC, while VirAB itself plays a role in response to kanamycin and tetracycline in L. monocytogenes EGD-e.IMPORTANCE This report describes TCS/ABC transporter modules characterized in Listeria monocytogenes EGD-e. The modules consist of the VirSR TCS and the VirAB and AnrAB ABC transporters. Our results showed that this system is involved in nisin and bacitracin resistance, as well as resistance to cephalosporins, ethidium bromide (EtBr), and benzalkonium chloride (BC). In this system, VirAB is responsible only for antimicrobial sensing and signaling by VirSR, while AnrAB contributes to transportation of antimicrobials. Interestingly, VirAB itself, rather than the VirAB-VirSR-AnrAB system as a whole, contributes to kanamycin and tetracycline resistance.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Listeria monocytogenes/genética , Listeria monocytogenes/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
Sustainable development has become a strategic consensus in response to the global environmental problems. Green credit is a major policy innovation that promotes the transformation of economic development mode and industrial green transformation (IGT). Using provincial panel data from 2005 to 2020, we investigate the effect of green credit on IGT using a systematic GMM model, a dynamic threshold model, as well as the possible nonlinear relationship. Benchmark regression results show that green credit can encourage industrial green transformation. In addition, there is a single green credit threshold with a value of 0.2612. The trend is "negative to positive". According to the moderating effect results, environmental regulation moderates in a negative manner. As environmental regulations become more stringent, the contribution of green credit to IGT will diminish. The intermediary mechanism test demonstrates that green technology innovation and marketization level play a partial intermediary role. Heterogeneity testing confirms that the function of green credit in promoting industrial green transformation is more significant in regions with a higher level of green finance development and a lower degree of government intervention. Therefore, the government should encourage financial institutions to provide green credit products and services to meet the financing needs of different green projects, thereby facilitating the industrial green transformation.
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Background: The adverse clinical endpoints of cardiovascular and kidney diseases are correlated with increased serum phosphate levels. However, in critically ill patients with coronary heart disease (CHD) accompanied by chronic kidney disease (CKD), the prognostic value of serum phosphate remains unclear. Methods: Patients' medical records from the Medical Information Mart for Intensive Care IV database who had concomitant CKD and CHD were classified into four distinct groups in this large retrospective observational cohort study based on the quartiles of serum phosphate levels. Vital status and the duration of hospital and ICU stays within the short-term follow-up periods of 30 and 90 days constituted the primary outcomes. All-cause mortality in the intensive care unit (ICU) and hospital constituted the secondary outcomes. Further, the Cox proportional hazard and restricted cubic spline (RCS) regression models were employed to ascertain how serum phosphate levels correlated with the primary outcomes. In addition, the occurrence rate of the secondary outcomes across the four quartiles was determined utilizing the Kaplan-Meier method. Results: Among the total 3,557 patients (67.6% male) included, the hospital and ICU all-cause mortality rates were 14.6% and 10%, separately. Higher quartiles of serum phosphate concentrations were associated with shorter short-term survival rates, as shown by the Kaplan-Meier curves. Additionally, the Cox proportional hazards analysis illustrated that serum phosphate was independently linked to a higher death risk in the hospital [HR, 1.10 (95% CI: 1.03-1.18), P = 0.007] and ICU [HR, 1.14 (95% CI: 1.07-1.22), P < 0.001]. Lastly, the RCS regression models suggested a robust non-linear correlation between serum phosphate concentrations and death risk in the ICU and hospital (both P for non-linearity <0.001). Conclusions: The prognostic value of serum phosphate is significant in critically ill patients with CHD accompanied by CKD. Furthermore, serum phosphate is potentially valuable for identifying patients with this concomitant condition.