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This study was performed to investigate the inhibitory mechanisms of 3 plant polyphenols, grape seed extract (GSE), lotus seed proanthocyanidins (LSPC) and lotus root polyphenol extract (LRPE), against Shewanella putrefaciens. Their antibacterial effects were determined in terms of minimum inhibitory concentration (MIC) and the growth curve of S. putrefaciens. By scanning electron microscopy (SEM), relative conductivity, propyridine iodide (PI) staining, alkaline phosphatase (AKP) activity, extracellular protein content, nucleic acid leakage, Na+ K+ -ATPase activity and membrane protein fluorescence analysis, the antibacterial mechanism was explored. The results showed that the MICs of GSE, LRPE and LSPC were 31.25, 62.25 and 125.00 μg/mL, respectively. After S. putrefaciens was treated with the polyphenols, the position of membrane proteins was changed, the fluorescence intensity was reduced, the morphology was altered, the surface became wrinkled and sunken, and the growth was significantly inhibited. In addition, the activity of extracellular AKP, the contents of nucleic acid and extracellular protein in the bacterial suspension, relative conductivity and PI intake were significantly increased, and Na+ K+-ATPase was inactivated to a certain extent, thereby leading to cell death.

Chitosan nanoparticle is becoming an excellent carrier for the delivery of bioactive components due to the advantages of simple preparation, low cost and high biocompatibility. Previous studies have shown that chitosan/sodium tripolyphosphate (CS/TPP) and chitosan/flaxseed gum (CS/FG) nanoparticles loaded with bighead carp peptides (BCP) have the advantages of small particle size, high encapsulation rate and significant slow-release effect. This study explored the effects of ionic strength, pH, simulated digestion and storage time on the preparation of chitosan/sodium tripolyphosphate (CS/TPP-BCP) and chitosan/flaxseed gum (CS/FG-BCP) nanoparticles, and evaluated the extracellular lactate dehydrogenase content and antioxidant capacity in vivo of Caco-2 cells treated with the chitosan nanoparticles and their cellular uptake. The results showed that the two kinds of chitosan nanoparticles were stable under acidic conditions and sensitive to a solution with opposite charges. The stability of the nanoparticles loaded with bighead peptides was higher than that of free peptides and both nanoparticles showed higher biocompatibility and cell uptake.

With the transformation and development of China's economy and society, the state attaches great importance to the equalization of public services to meet the growing demand for a better life. Museums are not only one of the most important needs of people's spiritual culture but are also an important part of the public cultural service system. Their reasonable layout has an important impact on the equalization of basic public services. Therefore, research on the temporal and spatial evolution of museums has become one of the hotspots of related disciplines, and is of great significance to deepen the basic public service theory. This study selects a list of museums from 1990 to 2018 and uses a nuclear density analysis, standard deviation ellipse, spatial autocorrelation, and geographic detector model, to analyze the evolution trend of museum quantity, evolution characteristics of spatial distribution mode, law of spatial differentiation, and influencing factors of the temporal and spatial distribution of the museums. The results show that: 1) in terms of quantity evolution trend, there are significant differences in the number of museums from 1990-2000, 2000-2010, and 2010-2018, with a gradual increase in the number. Overall, the number of museums showed an accelerated growth trend from 1990-2018. The differences between the East and West are obvious. The number of museums in the eastern region is dense and the development is rapid; contrastingly, the number of museums in the central and western regions is sparse and development is relatively slow. 2) In terms of the evolution of spatial distribution mode, over time, Chinese museums continue to gather spatially and gradually evolve from "single center" distribution mode to "multi center" distribution mode, and the degree of agglomeration continues to improve. 3) The standard deviation ellipse analysis shows that from 1990-2018, the center of gravity of the Chinese museums was always located in the East; the center of gravity shifted slightly over time, and the moving track was about "Z." 4) In terms of the spatial differentiation law, there has been a significant spatial agglomeration process of Chinese museums since 1990, forming a pattern of "hot in the East and cold in the west". The middle and lower reaches of the Yangtze River are the hotspots of Chinese museums, and Xinjiang and Tibet are always in the cold spots. Additionally, the scope of hotspots continues to expand annually, extending to the northwest inland, which is consistent with China's strategy of "equalization of public cultural services" in recent years; it is also conducive to breaking the layout of public cultural facilities that are "strong in the East and weak in the West." 5) In terms of influencing factors, museum spatial differentiation is the result of the comprehensive action of multiple factors, which is mainly affected by the economy, society, policy, culture, and education. Among them, policy, cultural, and educational factors are the main influencing factors of museum spatial differentiation, followed by social factors, and economic factors are the general factors affecting its distribution.

The synergistic improvement in urban resilience and low-carbon development level is significant for mitigating and adapting to climate change, achieving the 'dual carbon goal' and promoting sustainable urban development. By constructing a comprehensive evaluation index system of urban resilience and low-carbon development, this study quantitatively measures the level of urban resilience and low-carbon development of the Central Plains Urban Agglomeration (CPUA) from 2009 to 2021. Further, the coupling coordination degree model and geographical detector explore the spatial and temporal evolution pattern and driving factors of the coupling and coordination (CCD) of urban resilience and low-carbon development. The results show the following: (1) From 2009 to 2021, urban resilience shows a good momentum of continuous rise, and the spatial distribution pattern is 'high in the northeast and low in southwest'. Low-carbon development is characterized by the development trend of 'first decline and then rise', forming a spatial distribution pattern of 'high in the south and low in the northwest'. (2) The CCD also shows a rising development trend. The type of coupling and coordination is mainly reluctant coordination. (3) The CCD shows a significant spatial correlation, and the degree of spatial agglomeration shows a downward trend. (4) The level of economic development and the level of scientific and technological innovation are the main two driving forces for the spatial differentiation of the coordinated development of the two systems. In addition, the explanatory power of the interaction of various influencing factors was significantly enhanced. In a word, this study was helpful to clarify further the spatial interaction between urban resilience and low-carbon development and also to provide experience and reference for low-carbon resilience construction and high-quality development of other urban agglomerations in the world. [ABSTRACT FROM AUTHOR]

Transformation and development performance evaluation and obstacle factor research are standard and important bases for measuring the transformation of mature resource cities. Based on the connotation of transformational development, this paper presents the selection of indices for the construction of a measurement index system that covers four aspects: economics, people's well-being, resources, and the ecological environment. Taking Jinzhong City as an example, this study measures the implementation effect of sustainable development planning in resource cities and applies the entropy-weight TOPSIS method and obstacle degree model to evaluate its transformation and development performance and diagnose obstacle factors from 2007 to 2020. The results are as follows: (1) Jinzhong City has made remarkable achievements in transitional development. In the past 14 years, transformation performance has increased from 0.260 to 0.711, and there has been a change from the fair transformation stage to the good transformation stage. (2) The transformational development of Jinzhong City presents two phases: the initial exploratory phase (2007~2013) and the steadily improving phase (2014~2020). The four systems differ significantly in their drive for transformational development in the two stages. (3) The main obstacle factors for the transformation and development of Jinzhong City show stage differences. However, as a whole, economic development and the ecological environment were the main obstacle factors constraining the transformation and development of the city. Hence, it is essential for mature coal resource cities to improve transformation in the future and construct a long-term mechanism for sustainable development, cultivating continuous alternative industries and improving the ecological environment and the security of people's livelihoods. [ABSTRACT FROM AUTHOR]

Environmental regulation (ER) is a crucial tool used by governments to intervene in the environmental practices of enterprises, and it is recognized as a significant avenue to impact industrial ecological efficiency (IEE). This study uses the superefficiency SBM model to determine provincial IEE scores. Then, a panel smooth transition regression (PSTR) model is used to explore the effects of ER on IEE transition at different stages of economic growth. The main findings are as follows: Firstly, China's IEE showed an overall upward trend, with small increments over the past two decades. Regions with higher IEE were mainly located in the east, while those with lower IEE were mostly in the less economically developed west. Secondly, the PSTR model revealed that ER had varying impacts on IEE at different stages of economic growth. ER positively influenced IEE in the early stages of economic growth. However, after surpassing the threshold of economic growth, ER began to contribute to reducing IEE scores. In addition to these findings, this study proposes a series of policy recommendations to strengthen IEE. [ABSTRACT FROM AUTHOR]

Hemorrhage control, especially noncompressible wound hemostasis, is a tremendous challenge in military injuries and other traumas worldwide. Here, a cryogelation strategy and subsequent solvent exchange are developed for the hydrogen bond‐induced self‐assembly of chitosan fibers and the production of fast expandable chitosan cryogel. Importantly, the ambient drying process facilitates the repeatable deformation performance of the shape‐memory cryogel with a response time of ≈1.7 s. Due to the capillary‐like structure of the cryogel and high hydrophilicity, rapid shape recovery is accompanied by 41 times water absorption ability. It is further demonstrated that chitosan cryogel is beneficial for in situ tissue regeneration by taking advantage of the biodegradability and biocompatibility of chitosan. Thus, chitosan cryogels prepared by this simple and benign method should have efficient hemostatic effect on noncompressible bleeding and severe fatal high‐pressure hemorrhage. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis is associated with significant morbidity and mortality. Identifying factors that affect the risk of developing severe disease could influence management. Plasma levels of renalase, an anti-inflammatory secretory protein, dramatically decrease in a murine acute pancreatitis model. We assessed this response in hospitalized acute pancreatitis patients to determine if reduced plasma renalase levels occur in humans. Plasma samples were prospectively and sequentially collected from patients hospitalized for acute pancreatitis. Two forms of plasma renalase, native (no acid) and acidified, were measured by ELISA and RNLS levels were compared between healthy controls and patients with mild and severe disease (defined as APACHE-II score ≥7) using nonparametric statistical analysis. Control (33) and acute pancreatitis (mild, 230 (76.7%) and severe, 70 (23.3%) patients were studied. Acidified RNLS levels were lower in pancreatitis patients: Control: 10.1 μg/ml, Mild 5.1 μg/ml, Severe 6.0 μg/ml; p < 0.001. Native RNLS levels were increased in AP: Control: 0.4 μg/ml, Mild 0.9 μg g/ml, Severe 1.2 μg/ml p < 0.001; those with severe AP trended to have higher native RNLS levels than those with mild disease (p = 0.056). In patients with severe AP, higher APACHE-II scores at 24 h after admission correlated with lower acid-sensitive RNLS levels on admission (r = −0.31, p = 0.023). Low plasma acidified RNLS levels, and increased native RNLS levels are associated with AP. Additional studies should assess the clinical correlation between plasma RNLS levels and AP severity and outcomes. [ABSTRACT FROM AUTHOR]

Problem definition: Airports and airlines have been challenged to improve decision making by producing accurate forecasts in real time. We develop a two-phased predictive system that produces forecasts of transfer passenger flows at an airport. In the first phase, the system predicts the distribution of individual transfer passengers' connection times. In the second phase, the system samples from the distribution of individual connection times and produces distributional forecasts for the number of passengers arriving at the immigration and security areas. Academic/practical relevance: To our knowledge, this work is the first to apply machine learning for predicting real-time distributional forecasts of journeys in an airport using passenger level data. Better forecasts of these journeys can help optimize passenger experience and improve airport resource deployment. Methodology: The predictive system developed is based on a regression tree combined with copula-based simulations. We generalize the tree method to predict distributions, moving beyond point forecasts. We also formulate a newsvendor-based resourcing problem to evaluate decisions made by applying the new predictive system. Results: We show that, when compared with benchmarks, our two-phased approach is more accurate in predicting both connection times and passenger flows. Our approach also has the potential to reduce resourcing costs at the immigration and transfer security areas. Managerial implications: Our predictive system can produce accurate forecasts frequently and in real time. With these forecasts, an airport's operating team can make data-driven decisions, identify late passengers, and assist them to make their connections. The airport can also update its resourcing plans based on the prediction of passenger flows. Our predictive system can be generalized to other operations management domains, such as hospitals or theme parks, in which customer flows need to be accurately predicted. Funding: This work was funded by Eurocontrol (APOC Business Process Reengineering Big Data Study) [Grant 15-220643-AWP6.3.1]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2021.0975. [ABSTRACT FROM AUTHOR]

Aberrant blood vessel formation contributes to a wide variety of pathologies, and factors that regulate angiogenesis are attractive therapeutic targets. Endothelial and smooth muscle cell-derived neuropilin-like protein (ESDN) is a neuropilin-related transmembrane protein expressed in ECs; however, its potential effect on VEGF responses remains undefined. Here, we generated global and EC-specific Esdn knockout mice and demonstrated that ESDN promotes VEGF-induced human and murine EC proliferation and migration. Deletion of Esdn in the mouse interfered with adult and developmental angiogenesis, and knockdown of the Esdn homolog (dcbld2) in zebrafish impaired normal vascular development. Loss of ESDN in ECs blunted VEGF responses in vivo and attenuated VEGF-induced VEGFR-2 signaling without altering VEGF receptor or neuropilin expression. Finally, we found that ESDN associates with VEGFR-2 and regulates its complex formation with negative regulators of VEGF signaling, protein tyrosine phosphatases PTP1B and TC-PTP, and VE-cadherin. These findings establish ESDN as a regulator of VEGF responses in ECs that acts through a mechanism distinct from neuropilins. As such, ESDN may serve as a therapeutic target for angiogenesis regulation., Introduction Angiogenesis is a tightly regulated process during development and growth, and wound healing in adult organisms. Dysregulated angiogenesis, whether inadequate or exaggerated, con-tributes to a wide variety of pathologies, [...]

To analyze the differences in the spatial and temporal distribution patterns of online attention to sudden torrential rain public events in Shanxi and Henan provinces in China, and their influencing factors, the Baidu index search platform was used to obtain the online attention of 31 provinces (autonomous regions and municipalities directly under the central government) nationwide for the 20 July 2021 to 9 August 2021 Henan torrential rain and the 5 October 2021 to 25 October 2021 Shanxi torrential rain. The geographical concentration index, the coefficient of variation, the Moran index, and the Pearson correlation were used to analyse the spatial and temporal distribution characteristics of the online attention of the floods in Shanxi and Henan and their influencing factors. The study shows that: (1) from a temporal perspective, the daily internet attention of both the Shanxi and Henan torrential rain reached its highest value on the third day, showing a sharp rise followed by a sharp fall in an inverted "V" pattern, and compared to the prolonged and continuous torrential rain in Shanxi, the short-lived precipitation and broken ring of the Henan torrential rain were seriously urgent, showing a higher internet attention. For example, the highest daily attention in Shanxi was only 73,643, while the highest daily attention in Henan was 56,054, which is 7.6 times higher than the former. The Geographical Concentration (G) index of internet attention for torrential rain in Shanxi increased from 1.55 to 8.25 within three weeks, with attention shifting from scattered to concentrated, while the G-index for torrential rain in Henan showed an inverted "V" shape; the Coefficient of Variation (CV) index for torrential rain in both provinces showed a downward trend within three weeks. (2) In terms of spatial distribution, the regional distribution of the network concern about the torrential rain in Shanxi and Henan is uneven. The provinces and cities with a higher concern about the torrential rain in Shanxi are mainly some eastern provinces and cities, such as Jiangsu, Beijing, Zhejiang, Fujian, Hainan, etc., who have signed coal protection agreements with Shanxi. The provinces and cities with a higher concern about the torrential rain in Henan are mainly the economically developed coastal provinces or provinces adjacent to Henan, such as Beijing, Zhejiang, Shandong, and Shaanxi, etc. The concern of each city for the torrential rain in the two provinces is in line with the law of distance decay. (3) In terms of influencing factors, the level of regional economic development, demographic factors, and Internet penetration and distance all have a certain influence on the level of attention to sudden torrential rain, and the study found that the level of economic development and demographic factors have the most significant influence on the level of internet attention. [ABSTRACT FROM AUTHOR]

COVID-19 has killed millions of people worldwide. As a result, medical and health resources continue to be strained, posing a great threat to people's safety and economic and social development. This paper built the index system of influencing factors of medical and health resources containing the economy, population and society, and then classified Taiyuan into three types of regions by cluster analysis. The Gini coefficient, Theil index and agglomeration degree were then used to analyze the spatial distribution of medical and health resources allocation, and its influencing factors were studied by grey relational analysis. It was found that the population allocation of medical and health resources in Taiyuan was better than area allocation. Population has the greatest influence on the allocation of medical and health resources, followed by society and the economy. The more developed the regional economy, the more diversified the main influencing factors, and the more adjustment and control choices of medical and health resources allocation. Suggestions for optimal allocation were put forward in order to fully utilize the limited medical and health resources, effectively respond to the epidemic needs, promote the sustainable development of resources, protect the health of residents, and improve social benefits. [ABSTRACT FROM AUTHOR]

The molecular and cellular pathogenesis of leptospirosis remains poorly understood. Based on comparative bacterial genomics data, we recently identified the hypothetical PF07598 gene family as encoding secreted exotoxins (VM proteins) that mediate cytotoxicity in vitro. To address whether VM proteins mediate in vivo leptospirosis pathogenesis, we tested the hypothesis that VM protein immunization of mice would protect against lethal challenge infection and reduce bacterial load in key target organs. C3H/HeJ mice were immunized with recombinant E. coli- produced, endotoxin-free, leptospiral VM proteins (derived from L. interrogans serovar Lai) in combination with the human-compatible adjuvant, glucopyranoside lipid A/squalene oil-in-water. Mice receiving full length recombinant VM proteins were protected from lethal challenge infection by L. interrogans serovar Canicola and had a 3-4 log10 reduction in bacterial load in the liver and kidney. These experiments show that immunization with recombinant VM proteins prevents leptospirosis clinical pathogenesis and leads to markedly reduced key target organ infection in this animal model. These data support the role of leptospiral VM proteins as virulence factors and suggest the possibility that a VM protein-based, serovar-independent, pan-leptospirosis vaccine may be feasible. [ABSTRACT FROM AUTHOR]

Flaviviruses, represented by Zika and dengue virus (ZIKV and DENV), are widely present around the world and cause various diseases with serious consequences. However, no antiviral drugs have been clinically approved for use against them. Azelnidipine (ALP) is a dihydropyridine calcium channel blocker and has been approved for use as an antihypertensive drug. In the present study, ALP was found to show potent anti-flavivirus activities in vitro and in vivo. ALP effectively prevented the cytopathic effect induced by ZIKV and DENV and inhibited the production of viral RNA and viral protein in a dose-dependent manner. Moreover, treatment with 0.3 mg/kg of ALP protected 88.89% of mice from lethal challenge. Furthermore, using the time-of-drug-addition assay, the enzymatic inhibition assay, the molecular docking, and the surface plasmon resonance assay, we revealed that ALP acted at the replication stage of the viral infection cycle by targeting the viral RNA-dependent RNA polymerase. These findings highlight the potential for the use of ALP as an antiviral agent to combat flavivirus infections. [ABSTRACT FROM AUTHOR]

Enterovirus infections can cause hand, foot, and mouth disease (HFDM), aseptic meningitis, encephalitis, myocarditis, and acute flaccid myelitis, leading to death of infants and young children. However, no specific antiviral drug is currently available for the treatment of this type of infection. The Unites States and United Kingdom health authorities recently approved a new antiviral drug, molnupiravir, for the treatment of COVID-19. In this study, we reported that molnupiravir (EIDD-2801) and its active form, EIDD-1931, have broad-spectrum anti-enterovirus potential. Our data showed that EIDD-1931 could significantly reduce the production of EV-A71 progeny virus and the expression of EV-A71 viral protein at non-cytotoxic concentrations. The results of the time-of-addition assay suggest that EIDD-1931 acts at the post-entry step, which is in accordance with its antiviral mechanism. The intraperitoneal administration of EIDD-1931 and EIDD-2801 protected 1-day-old ICR suckling mice from lethal EV-A71 challenge by reducing the viral load in various tissues of the infected mice. The pharmacokinetics analysis indicated that the plasma drug concentration overwhelmed the EC50 for enteroviruses, suggesting the clinical potential of molnupiravir against enteroviruses. Thus, molnupiravir along with its active form, EIDD-1931, may be a promising drug candidate against enterovirus infections. [ABSTRACT FROM AUTHOR]

Climate change has been considerable concerned because of the increasing greenhouse gas (GHG) emissions. Gansu province is a typical less-developed and heavy chemical industrial province, its CO2 emission per unit of the gross domestic product (GDP) is 252.52 ton per million Chinese yuan (t/M-CNY) in 2019, which is 48.42% more than national average value. Gansu province faces the following dual pressures including maintaining economic growth and reducing carbon dioxide (CO2) emissions. This paper establishes a low carbon development system dynamics model in order to investigate the effects of four carbon reduction measures (technical progress, industrial transformation, fuel substitution, and low carbon awareness) on reducing CO2 emission over the period of 2020–2030. The simulation results indicate that, without direct intervention, the CO2 emissions per unit of GDP is projected to be 171.34 t/M-CNY by 2030. While utilizing technical progress, implementing industrial transformation, fuel substitution, and low carbon awareness could potentially be 2.12%, 3.33%, 0.72% and 1.27%, respectively less than that. For the sake of achieving the goal of CO2 reduction in the long run, the local government should address today's industrial transformation and adopt reasonable combination of adjustment and control policies immediately. [ABSTRACT FROM AUTHOR]