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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.

Influenza viruses remain a major threat to human health. Four classes of drugs have been approved for the prevention and treatment of influenza infections. Oseltamivir, a neuraminidase inhibitor, is a first-line anti-influenza drug, and baloxavir is part of the newest generation of anti-influenza drugs that targets the viral polymerase. The emergence of drug resistance has reduced the efficacy of established antiviral drugs. Combination therapy is one of the options for controlling drug resistance and enhancing therapeutical efficacies. Here, we evaluate the antiviral effects of baloxavir combined with neuraminidase inhibitors (NAIs) against wild-type influenza viruses, as well as influenza viruses with drug-resistance mutations. The combination of baloxavir with NAIs led to significant synergistic effects; however, the combination of baloxavir with laninamivir failed to result in a synergistic effect on influenza B viruses. Considering the rapid emergence of drug resistance to baloxavir, we believe that these results will be beneficial for combined drug use against influenza. [ABSTRACT FROM AUTHOR]

Acute pancreatitis, an acute inflammatory injury of the pancreas, lacks a specific treatment. The circulatory protein renalase is produced by the kidney and other tissues and has potent anti-inflammatory and prosurvival properties. Recombinant renalase can reduce the severity of mild cerulein pancreatitis; the activity is contained in a conserved 20 aa renalase site (RP220). Here, we investigated the therapeutic effects of renalase on pancreatitis using two clinically relevant models of acute pancreatitis. The ability of peptides containing the RP220 site to reduce injury in a 1-day post-endoscopic retrograde cholangiopancreatography (ERCP) and a 2-day severe cerulein induced in mice was examined. The initial dose of renalase peptides was given either prophylactically (before) or therapeutically (after) the initiation of the disease. Samples were collected to determine early pancreatitis responses (tissue edema, plasma amylase, active zymogens) and later histologic tissue injury and inflammatory changes. In both preclinical models, renalase peptides significantly reduced histologic damage associated with pancreatitis, especially inflammation, necrosis, and overall injury. Quantifying inflammation using specific immunohistochemical markers demonstrated that renalase peptides significantly reduced overall bone marrow-derived inflammation and neutrophils and macrophage populations in both models. In the severe cerulein model, administering a renalase peptide with or without pretreatment significantly reduced injury. Pancreatitis and renalase peptide effects appeared to be the same in female and male mice. These studies suggest renalase peptides that retain the anti-inflammatory and prosurvival properties of recombinant renalase can reduce the severity of acute pancreatitis and might be attractive candidates for therapeutic development. NEW & NOTEWORTHY: Renalase is a secretory protein. The prosurvival and anti-inflammatory effects of the whole molecule are contained in a 20 aa renalase site (RP220). Systemic treatment with peptides containing this renalase site reduced the severity of post-endoscopic retrograde cholangiopancreatography (ERCP) and severe cerulein pancreatitis in mouse models. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection. [ABSTRACT FROM AUTHOR]

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, [...]