Tubulovascular protection from protease-activated receptor-1 depletion during AKI-to-CKD transition.

BACKGROUND: Thromboembolic events are prevalent in chronic kidney disease (CKD) patients due to increased thrombin generation leading to a hypercoagulable state. We previously demonstrated that inhibition of protease-activated receptor-1 (PAR-1) by vorapaxar reduces kidney fibrosis. METHODS: We used an animal model of unilateral ischemia-reperfusion (UIRI)-induced CKD to explore the tubulovascular crosstalk mechanisms of PAR-1 in AKI-to-CKD transition. RESULTS: During the early phase of AKI, PAR-1 deficient mice exhibited reduced kidney inflammation, vascular injury and preserved endothelial integrity and capillary permeability. During the transition phase to CKD, PAR-1 deficiency preserved kidney function and diminished tubulointerstitial fibrosis via downregulated TGF-ß/Smad signaling. Maladaptive repair in the microvasculature after AKI further exacerbated focal hypoxia with capillary rarefaction, which was rescued by stabilization of HIF and increased tubular VEGFA in PAR-1 deficient mice. Chronic inflammation was also prevented with reduced kidney infiltration by both M1- and M2- polarized macrophages. In thrombin-induced human dermal microvascular endothelial cells (HDMECs), PAR-1 mediated vascular injury through activation of NFκB and ERK MAPK pathways. Gene silencing of PAR-1 exerted microvascular protection via a tubulovascular crosstalk mechanism during hypoxia in HDMECs. Finally, pharmacologic blockade of PAR-1 with vorapaxar improved kidney morphology, promoted vascular regenerative capacity, and reduced inflammation and fibrosis depending on the time of initiation. CONCLUSIONS: Our findings elucidate a detrimental role of PAR-1 in vascular dysfunction and profibrotic responses upon tissue injury during AKI-to-CKD transition and provide an attractive therapeutic strategy for post-injury repair in AKI.

Mussel-Inspired Caries Management Strategy: Constructing a Tribioactive Tooth Surface with Remineralization, Antibiofilm, and Anti-inflammation Activity.

Dental caries is a common chronic oral disease in humans resulting from tooth demineralization caused by acid production of bacterial plaque, which leads to the destruction of enamel and dentin and oral inflammation. However, it is still a challenge that the function of natural active ingredients in currently available oral care products is not comprehensive, especially the lack of remineralization. Here, inspired by the strong biological adhesion ability of mussels and ancient oral disease plant therapy, a multifunctional strategy is proposed to construct a bioactive tooth surface to treat dental caries. It has been demonstrated that the Turkish gall extract (TGE) can inhibit adhesion of cariogenic bacteria Streptococcus mutans and Actinomyces viscosus and destroy biofilms on the tooth surface. Meanwhile, TGE can reduce the expression of inflammatory factors. Notably, the TGE coating can induce the growth of hydroxyapatite (HAP) crystals in vivo and in vitro, recovering the enamel mechanical properties under normal oral conditions. MD simulations interpreted the adsorption mechanism by which the hydroxyl groups in TGE bind to phosphate group (PO43-) on the tooth surface, attracting calcium ions (Ca2+) as nucleation sites for remineralization. This work underlines the importance of TGE coating in remineralization, antibiofilm, and anti-inflammation activity as a promising strategy for dental caries.

A systematic review of published literature on mosquito control action thresholds across the world.

BACKGROUND: Despite the use of numerous methods of control measures, mosquito populations and mosquito-borne diseases are still increasing globally. Evidence-based action thresholds to initiate or intensify control activities have been identified as essential in reducing mosquito populations to required levels at the correct/optimal time. This systematic review was conducted to identify different mosquito control action thresholds existing across the world and associated surveillance and implementation characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Searches for literature published from 2010 up to 2021 were performed using two search engines, Google Scholar and PubMed Central, according to PRISMA guidelines. A set of inclusion/exclusion criteria were identified and of the 1,485 initial selections, only 87 were included in the final review. Thirty inclusions reported originally generated thresholds. Thirteen inclusions were with statistical models that seemed intended to be continuously utilized to test the exceedance of thresholds in a specific region. There was another set of 44 inclusions that solely mentioned previously generated thresholds. The inclusions with "epidemiological thresholds" outnumbered those with "entomological thresholds". Most of the inclusions came from Asia and those thresholds were targeted toward Aedes and dengue control. Overall, mosquito counts (adult and larval) and climatic variables (temperature and rainfall) were the most used parameters in thresholds. The associated surveillance and implementation characteristics of the identified thresholds are discussed here. CONCLUSIONS/SIGNIFICANCE: The review identified 87 publications with different mosquito control thresholds developed across the world and published during the last decade. Associated surveillance and implementation characteristics will help organize surveillance systems targeting the development and implementation of action thresholds, as well as direct awareness towards already existing thresholds for those with programs lacking available resources for comprehensive surveillance systems. The findings of the review highlight data gaps and areas of focus to fill in the action threshold compartment of the IVM toolbox.

Self-Healable, Solvent Response Cellulose Nanocrystal/Waterborne Polyurethane Nanocomposites with Encryption Capability.

Cellulose nanocrystal (CNC)-based chiral nematic structure is widely used in stimulus response and sensing. A popular area of research is enhancing the mechanical characteristics and environmental adaptability of chiral nematic materials. In this paper, a flexible photonic film with self-healing ability (FPFS) was prepared by combining waterborne polyurethane containing dynamic covalent disulfide bonds (SSWPU) with CNC. The results found that the FPFS showed excellent toughness under the action of stretching, bending, twisting, and folding. The FPFS exhibited an amazing self-healing efficiency, which can be self-healed within 2 h at room temperature. Moreover, the FPFS could respond immediately and produce reversible color change when it was soaked in typical solvents. In addition, when ethanol was used as ink to paint on the FPFS, a visible pattern only under polarized light was formed. This study offers fresh perspectives in the areas of self-healing, biological anticounterfeiting, solvent response, and flexible photonic materials.

Recent advances in self-healing polyurethane based on dynamic covalent bonds combined with other self-healing methods.

To meet more application requirements, improving mechanical properties and self-healing efficiency has become the focus of current research on self-healing PU. The competitive relationship between self-healing ability and mechanical properties cannot be avoided by a single self-healing method. To address this problem, a growing number of studies have combined dynamic covalent bonding with other self-healing methods to construct the PU structure. This review summarizes recent studies on PU materials that combine typical dynamic covalent bonds with other self-healing methods. It mainly includes four parts: hydrogen bonding, metal coordination bonding, nanofillers combined with dynamic covalent bonding and multiple dynamic covalent bond bonding. The advantages and disadvantages of different self-healing methods and their significant role in improving self-healing ability and mechanical properties in PU networks are analyzed. At the same time, the possible challenges and research directions of self-healing PU materials in the future are discussed.

The influence of school inclusive education climate on physical education teachers' inclusive education competency: The mediating role of teachers' agency.

Introduction: Teachers' inclusive education competency is the key to the successful implementation of inclusive education. Under the background of China's vigorous development of inclusive education, the influence mechanism of inclusive education competency of Chinese physical education teachers has not been paid attention to. The present study concentrates on the relationships between school inclusive education climate, physical education teachers' agency, and inclusive education competency. Methods: Data were collected from 286 primary and junior high school physical education teachers through nationwide convenience sampling on the Internet in China by completing the School Inclusive Education Climate Scale, Physical Education Teachers' Agency Scale, PE Teachers' Inclusive Education Competency Scale. Results: Results of structural equation modelling revealed that school inclusive education climate had a significant effect on physical education teachers' agency. School inclusive education climate had a significant influence on physical education teachers' inclusive education competency. The mediation effect of physical education teachers' agency on the relationship between school inclusive education climate and inclusive education competency was significant as well. Discussion: These results demonstrate that school inclusive education climate plays a direct and indirect role in promoting physical education teachers' inclusive education competency.

Effects of slope aspect and age class on diseases of Juglans regia in Wild Walnut Nature Conservation Area of Xinjiang, China.

To understand the disease situation of vulnerable plant Juglans regia, we investigated the proportions of four diseases of J. regia with different age classes in different slope aspects in the Wild Walnut Nature Conservation Area of Xinjiang. We analyzed the correlation of disease types and disease grades with the diameter at breast height (DBH) of J. regia and slope aspects. The results showed that the main diseases of J. regia in the reserve were walnut brown spot disease (95.8%), walnut deadwood disease (90.5%), walnut black spot disease (74.4%), and walnut rot disease (7.7%). J. regia was susceptible to walnut brown spot disease in all the four slope aspects, with walnut deadwood disease on shady and semi-shady slopes, walnut black spot disease on sunny and shady slopes, and walnut rot disease on semi-sunny and semi-shady slopes. The proportion of diseased plants with the four diseases decreased with the increases of disease grades (1-4 grades) in the four slope aspects. Across the four slope aspects, the middle-aged trees had the largest proportion of walnut deadwood disease, walnut black spot disease and walnut brown spot disease, followed by old trees and young trees. No diseased seedlings were found. Walnut rot disease only occurred in old trees. There was significant positive correlation between DBH of J. regia and the four diseases. Walnut black spot disease had significant negative correlation with slope aspect. There was correlation between different disease grades of walnut deadwood disease, walnut rot disease and walnut black spot disease with DBH and slope aspects.

Influence of Cathode Channel Parameters and Fan Duty Ratio on Low Power Forced-Convection Open-Cathode Proton Exchange Membrane Fuel Cell Stack.

The open-cathode forced-convection proton exchange membrane fuel cell has emerged as a viable option for portable energy sources. The forced-convection open-cathode mode, however, makes the cell's performance sensitive to changes in the cathode channel and fan parameters. In this study, small fuel cell stacks with varying cathode channel depths, widths, and width-rib ratios were assembled, and the effects of different cathode channel parameters and fan duty ratios on cell performance were investigated. The experimental results show that changing the cathode channel parameters has a significant impact on oxidant supply. When the channel width is increased, the cell performance increases first, then decreases. The cell performance decreases as the channel width-rib ratio increases. The performance of the cell improves as the cathode channel depth increases. Furthermore, the experimental results show that decreasing the duty ratio of the fan and using moderate heating improves cell performance.

Overlooked Spherical Nanoparticles Exist in Plant Extracts: From Mechanism to Therapeutic Applications.

To date, plant medicine research has focused mainly on the chemical compositions of plant extracts and their medicinal effects. However, the therapeutic or toxic effects of nanoparticles in plant extracts remain unclear. In this study, large numbers of spherical nanoparticles were discovered in some plant extracts. Nanoparticles in Turkish galls extracts were used as an example to examine their pH responsiveness, free radical scavenging, and antibacterial capabilities. By utilizing the underlying formation mechanism of these nanoparticles, a general platform to produce spherical nanoparticles via direct self-assembly of Turkish gall extracts and various functional proteins was developed. The results showed that the nanoparticles retained both the antibacterial ability and intracellular carrier ability of the original protein or catechol. This work introduces a new member of the plant-derived edible nanoparticle (PDEN) family, establishes a simple and versatile platform for mass production nanoparticles, and provides new insight into the formation mechanism of nanoparticles during plant extraction.

Conceptual Model, Experiment and Numerical Simulation of Diaphragm Wall Leakage Detection Using Distributed Optical Fiber.

Leakage in the diaphragm wall is difficult to detect in deep foundation pits. In this study, the conceptual model of active and passive thermal leak detection methods was proposed according to the occurrence of temperature field anomalies caused by seepage. Experiments were performed using a heating system and an optical fiber temperature measurement system to verify the thermal leakage detection systems. Numerical simulations were performed to understand the mechanism of the detecting method. Results indicated that the optical cable could detect the low-temperature anomaly in the active temperature field leak detection. The arrangement method of the leakage detection system was also presented in actual engineering.

What Matters on Rural Left-Behind Children's Problem Behavior: Family Socioeconomic Status or Perceived Discrimination.

With the acceleration of China's industrialization and urbanization, there is a large number of left-behind children in China who are reported with more challenges in development. The study aims to analyze the differences in family socioeconomic status (SES) and discrimination perception between left-behind children and non-left-behind children and further explore whether SES or discrimination perception has a greater impact on the problem behaviors of left-behind children. We found the family SES of left-behind children was significantly lower than that of non-left-behind children; left-behind children's perceived discrimination was significantly higher than that of non-left-behind children; perceived discrimination of left-behind children had a greater impact on their problem behavior than the family SES.

Photoaffinity labelling-based chemoproteomic strategy identifies PEBP1 as the target of ethyl gallate against macrophage activation.

Ulcerative colitis (UC) is an inflammatory disease of the colon with an unmet need for therapeutic targets. Ethyl gallate (EG) is a natural small molecule for UC treatment, but its cellular target is unknown. By labelling EG with a diazirine photocrosslinker and a click chemistry handle, we identified phosphatidyl-ethanolamine binding protein1 (PEBP1) as a direct cellular target of EG by forming hydrogen bonds with Asp70 and Tyr120. In particular, hydrogen/deuterium exchange mass spectrometry indicated that EG induced the sequence (residues 141-153) embedding to inhibit S153 phosphorylation of PEBP1. Additionally, the EG-mediated sequence (residues 108-122) exposure significantly enhanced PEBP1-Raf-1 interaction to block the downstream NF-κB inflammatory pathway in macrophages. Moreover, PEBP1 siRNA substantially reversed the EG-dependent down-regulation of the phosphorylation of IKKß, IκBα and NF-κB, demonstrating that the NF-κB signal functioned as an essential anti-inflammation mechanism of PEBP1. Collectively, we revealed PEBP1 as a previously undescribed cellular target in macrophages for UC therapy and identified a new allosteric site for PEBP1 biology study using EG as a chemical probe.

The long noncoding RNA Meg3 mediates TLR4-induced inflammation in experimental obstructive nephropathy.

Kidney inflammation contributes to the progression of chronic kidney disease (CKD). Modulation of Toll-like receptor 4 (TLR4) signaling is a potential therapeutic strategy for this pathology, but the regulatory mechanisms of TLR4 signaling in kidney tubular inflammation remains unclear. Here, we demonstrated that tubule-specific deletion of TLR4 in mice conferred protection against obstruction-induced kidney injury, with reduction in inflammatory cytokine production, macrophage infiltration and kidney fibrosis. Transcriptome analysis revealed a marked down-regulation of long noncoding RNA (lncRNA) Meg3 in the obstructed kidney from tubule-specific TLR4 knockout mice compared with wild-type control. Meg3 was also induced by lipopolysaccharide in tubular epithelial cells via a p53-dependent signaling pathway. Silencing of Meg3 suppressed LPS-induced cytokine production of CCL-2 and CXCL-2 and the activation of p38 MAPK pathway in vitro and ameliorated kidney fibrosis in mice with obstructive nephropathy. Together, these findings identify a proinflammatory role of lncRNA Meg3 in CKD and suggest a novel regulatory pathway in TLR4-driven inflammatory responses in tubular epithelial cells.

Biosensor-based active ingredient recognition system for screening TNF-α inhibitors from lotus leaves.

Erhuangquzhi granules (EQG) have been clinically proven to be effective in nonalcoholic steatohepatitis (NASH) treatment. However, the active components and molecular mechanisms remain unknown. This study aimed to screen active components targeting tumor necrosis factor α (TNF-α) in EQG for the treatment of NASH by a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). The amine-coupling method was used to immobilize recombinant TNF-α protein on an SPR chip, the specificity of the TNF-α-immobilized chip was validated, and nine medicinal herbs in EQG were prescreened. Nuciferine (NF), lirinidine (ID), and O-nornuciferine (NNF) from lotus leaves were found and identified as TNF-α ligands by UPLC‒MS/MS, and the affinity constants of NF, ID, and NNF to TNF-α were determined by SPR experiments (Kd = 61.19, 31.02, and 20.71 µM, respectively). NF, ID, and NNF inhibited TNF-α-induced apoptosis in L929 cells, the levels of secreted IL-6 and IL-1ß were reduced, and the phosphorylation of IKKß and IκB was inhibited in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In conclusion, a class of new active small-molecule TNF-α inhibitors was discovered, which also provides a valuable reference for the material basis and mechanism of EQG action in NASH treatment.

Ultrafine Core@Shell Cu1Au1@Cu1Pd3 Nanodots Synergized with 3D Porous N-Doped Graphene Nanosheets as a High-Performance Multifunctional Electrocatalyst.

Rationally combining designed supports and metal-based nanomaterials is effective to synergize their respective physicochemical and electrochemical properties for developing highly active and stable/durable electrocatalysts. Accordingly, in this work, sub-5 nm and monodispersed nanodots (NDs) with the special nanostructure of an ultrafine Cu1Au1 core and a 2-3-atomic-layer Cu1Pd3 shell are synthesized by a facile solvothermal method, which are further evenly and firmly anchored onto 3D porous N-doped graphene nanosheets (NGS) via a simple annealing (A) process. The as-obtained Cu1Au1@Cu1Pd3 NDs/NGS-A exhibits exceptional electrocatalytic activity and noble-metal utilization toward the alkaline oxygen reduction, methanol oxidation, and ethanol oxidation reactions, showing dozens-fold enhancements compared with commercial Pd/C and Pt/C. Besides, it also has excellent long-term electrochemical stability and electrocatalytic durability. Advanced and comprehensive experimental and theoretical analyses unveil the synthetic mechanism of the special core@shell nanostructure and further reveal the origins of the significantly enhanced electrocatalytic performance: (1) the prominent structural properties of NGS, (2) the ultrasmall and monodispersed size as well as the highly uniform morphology of the NDs-A, (3) the special Cu-Au-Pd alloy nanostructure with an ultrafine core and a subnanometer shell, and (4) the strong metal-support interaction. This work not only develops a facile method for fabricating the special metal-based ultrafine-core@ultrathin-shell nanostructure but also proposes an effective and practical design paradigm of comprehensively and rationally considering both supports and metal-based nanomaterials for realizing high-performance multifunctional electrocatalysts, which can be further expanded to other supports and metal-based nanomaterials for other energy-conversion or environmental (electro)catalytic applications.

Efficacy Evaluation of Medium-Chain Fatty Acids as Skin and Spatial Repellents Against Aedes aegypti (Diptera:Culicidae) Mosquitoes.

Fatty acids derived from natural oils are considered as perspective products for adoption as repellents. Fatty acids derived from coconut oil have shown promise as repellents. This study consisted of an olfactometer evaluation of new formulations containing medium-chain fatty acids for spatial repellency and an in laboratory arm-in cage study for contact repellency against Aedes aegypti L. mosquitoes. Six formulations each of capric acid and lauric acid were evaluated for spatial repellency. These formulations contained 0.28-10% of either capric acid or lauric acid as the active ingredients in a consumer friendly skin care formulation. Base formula without fatty acids was evaluated as control in spatial repellency evaluation. For the arm-in cage evaluations, six formulations of capric acid, one base formulation, and a 7% N,N-diethyl-m-toluamide (DEET) product were tested for contact repellency. For contact repellency, United States Department of Agriculture (USDA) standard repellent test cages were used to determine the complete protection time (CPT) of the different formulated repellents. Among all capric acid formulations tested, the concentration of 2.25% (wt) indicated the best level of spatial repellency, but not significantly different from other concentrations. None of the lauric acid concentrations showed any level of spatial repellency. In the arm-in-cage evaluations, the highest contact repellency resulted from 4.5% capric acid, which was significantly higher than 7% DEET and base formula.

Engineering crystal water in potassium ammonium vanadate for fast Zn-ion storage.

The effect of different annealing temperatures on the electrochemical performance of potassium ammonium vanadate (KNVO) was investigated, and the annealed KNVO regained H2O from the aqueous electrolyte to achieve an optimal structural water content during activation. In addition, the accompanying oxygen vacancies further promoted Zn2+ diffusion kinetics of the KNVO cathode in AZIBs and achieved excellent rate performance (344 mA h g-1 at 10 A g-1).

Can the marketization of urban land transfer improve energy efficiency?

Local government intervention in land resource allocation can lead to the misallocation of land resources and serious pollutant emissions. As an important market-oriented economic reform in China, the marketization of urban land transfer (MULT) might have the potential to contribute to improving resource allocation efficiency by curbing local government intervention. Therefore, this study aims to provide empirical evidence on the impact of MULT on energy efficiency. We improve the MULT evaluation method to test the mechanism through which MULT affects energy efficiency. The results show that, first, the proportion of land sold by allocation and listing methods, which is characterized by a low degree of marketization, has rapidly increased in recent years, lowering the overall level of MULT. Second, MULT has a direct and significant positive impact on improving energy efficiency. Third, the mechanism analysis indicates that MULT helps enhance energy efficiency by advancing industrial structure optimization and technological progress. Moreover, the heterogeneity analysis demonstrates that the impact of MULT on improving energy efficiency differs significantly in different reform stages and between central and peripheral cities. This study sheds light on the importance of land resource allocation in improving energy efficiency and thus has practical policy implications for promoting low-carbon energy transition in emerging countries.

Charge Density Wave in Kagome Lattice Intermetallic ScV_{6}Sn_{6}.

Materials hosting kagome lattices have drawn interest for the diverse magnetic and electronic states generated by geometric frustration. In the AV_{3}Sb_{5} compounds (A=K, Rb, Cs), stacked vanadium kagome layers give rise to unusual charge density waves (CDW) and superconductivity. Here we report single-crystal growth and characterization of ScV_{6}Sn_{6}, a hexagonal HfFe_{6}Ge_{6}-type compound that shares this structural motif. We identify a first-order phase transition at 92 K. Single crystal x-ray and neutron diffraction reveal a charge density wave modulation of the atomic lattice below this temperature. This is a distinctly different structural mode than that observed in the AV_{3}Sb_{5} compounds, but both modes have been anticipated in kagome metals. The diverse HfFe_{6}Ge_{6} family offers more opportunities to tune ScV_{6}Sn_{6} and explore density wave order in kagome lattice materials.