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Subarachnoid hemorrhage (SAH) is associated with high mortality and disability rates, and secondary white matter injury is an important cause of poor prognosis. However, whether brain capillary pericytes can directly affect the differentiation and maturation of oligodendrocyte precursor cells (OPCs) and subsequently affect white matter injury repair has still been revealed. This study was designed to investigate the effect of tissue inhibitor of metalloproteinase-3 (TIMP-3) for OPC differentiation and maturation. PDGFRβret/ret and wild-type C57B6J male mice were used to construct a mouse model of SAH via endovascular perforation in this study. Mice were also treated with vehicle, TIMP-3 RNAi or TIMP-3 RNAi + TIMP-3 after SAH. The effect of TIMP-3 on the differentiation and maturation of OPCs was determined using behavioral score, ELISA, transmission electron microscopy, immunofluorescence staining and cell culture. We found that TIMP-3 was secreted mainly by pericytes and that SAH and TIMP-3 RNAi caused a significant decrease in the TIMP-3 content, reaching a nadir at 24 h, followed by gradual recovery. In vitro, the myelin basic protein content of oligodendrocytes after oxyhemoglobin treatment was increased by TIMP-3 overexpression. The data indicates TIMP-3 could promote the differentiation and maturation of OPCs and subsequently improve neurological outcomes after SAH. Therefore, TIMP-3 could be beneficial for repair after white matter injury and could be a potential therapeutic target in SAH. [ABSTRACT FROM AUTHOR]

Transport infrastructure connectivity is a spatial basis for economic development and the spillover and feedback effects of transport infrastructure investment (TII) have become an impetus for economic growth (EG). However, existing research does not consider the spatial effects of TII on the gross EG and the multiple effects of TII on EG structures. To explore the spatial relationships and the functional routes between TII and EG, the spatial Durbin model (SDM) was used to empirically analyze the spatial spillover effect of TII on EG from geographical and economic perspectives based on panel data from 2007 to 2019 of 35 members and partners of the Organization for Economic Cooperation and Development (OECD+). On this basis, a structural equation model (SEM) was established to reveal the multiple mediating effects of TII on EG. Results show that (1) the SDM–SEM hybrid method can model the spatial spillover effect and function routes of TII on EG based on theoretical analysis and empirical research; (2) according to empirical analysis of the SDM model, the spatial spillover effect in high-income OECD+ countries shows a positive effect under the economic distance, while that in the upper-middle-income countries has a negative effect; (3) an empirical analysis of the function route model implies that TII in high-income OECD+ countries exerts multiple mediating effects and it mainly affects EG indirectly by means including industrial structure (IS), and the rate of contribution of the key function route FR3 is 67.25%. The following suggestions are proposed: (1) it is necessary to enhance the intensity of effective investment in transport infrastructure, focus on weak links of transport infrastructure, and pay attention to investment in burgeoning fields of the OECD+ countries; (2) differentiated TII strategies are required to be formulated according to development of OECD+ countries with different income levels; (3) it is necessary to give full play to the spatial spillover effect and multiple mediating effects of TII on EG and the TII structure should be optimized, so as to improve the economic benefits of TII. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular disease with high mortality and morbidity. In recent years, a large number of studies have focused on the mechanism of early brain injury (EBI) and delayed cerebral ischemia (DCI), including vasospasm, neurotoxicity of hematoma and neuroinflammatory storm, after aSAH. Despite considerable efforts, no novel drugs have significantly improved the prognosis of patients in phase III clinical trials, indicating the need to further re‐examine the multifactorial pathophysiological process that occurs after aSAH. The complex pathogenesis is reflected by the destruction of the dynamic balance of the energy metabolism in the nervous system after aSAH, which prevents the maintenance of normal neural function. This review focuses on the fluid metabolic pathways of the central nervous system (CNS), starting with ruptured aneurysms, and discusses the dysfunction of blood circulation, cerebrospinal fluid (CSF) circulation and the glymphatic system during disease progression. It also proposes a hypothesis on the metabolic disorder mechanism and potential therapeutic targets for aSAH patients. Cover Image for this issue: https://doi.org/10.1111/jnc.15384. [ABSTRACT FROM AUTHOR]

This study aims to theoretically explore the technological systems of tropical island zero-carbon building (TIZCB) to scientifically understand the characteristics of these buildings in terms of energy utilization, energy conservation, energy production, and intelligent system mechanisms. The purpose is to address the inefficiencies and resource wastage caused by the traditional segmented approach to building energy consumption management. Thus, it seeks to achieve a comprehensive understanding and application of the zero-carbon building (ZCB) technology system. This article focuses on the demands for energy-efficient comfort and innovative industrialization in construction. Through an analysis of the characteristics of TIZCB and an explanation of their concepts, it establishes a theoretical framework for examining the system mechanisms of these buildings. Additionally, it delves into the energy utilization, energy conservation, energy production, and intelligent system from macro, meso, and micro perspectives. This approach results in the development of an implementation strategy for studying the mechanisms of energy usage, conservation, and intelligent production systems in TIZCB. The results show that: (1) this study delves into the theoretical underpinnings of TIZCB, emphasizing their evolution from a foundation of low-carbon and near-zero energy consumption. The primary goal is to achieve zero carbon emissions during building operation, with reliance on renewable energy sources. Design considerations prioritize adaptation to high-temperature and high-humidity conditions, integrating regional culture along with the utilization of new materials and technologies. (2) A comprehensive technical framework for TIZCB is proposed, encompassing energy utilization, conservation, production capacity, and intelligent systems. Drawing from systems theory, control theory, and synergy theory, the research employs a macro–meso–micro analytical framework, offering extensive theoretical support for the practical aspects of design and optimization. (3) The research implementation plan establishes parameterized models, unveiling the intricate relationships with building performance. It provides optimized intelligent system design parameters for economically viable zero-carbon operations. This study contributes theoretical and practical support for the sustainable development of TIZCB and aligns with the dual carbon strategy in China and the clean energy free trade zone construction in Hainan. [ABSTRACT FROM AUTHOR]

Most patients with subarachnoid hemorrhage (SAH) do not exhibit brain parenchymal injury upon imaging but present significant blood–brain barrier (BBB) disruption and secondary neurological deficits. The aim of this study was to investigate whether stressed astrocytes act as a secondary barrier to exert a protective effect after SAH and to investigate the mechanism of glial limitan formation. A total of 204 adult male C57BL/6 mice and an endovascular perforation SAH model were employed. The spatiotemporal characteristics of glial limitan formation after SAH were determined by immunofluorescence staining and transmission electron microscopy. The molecular mechanisms by which pericytes regulate glia limitans formation were analyzed using polymerase chain reaction, Western blotting, immunofluorescence staining and ELISA in a pericyte-astrocyte contact coculture system. The findings were validated ex vivo and in vivo using lentiviruses and inhibitors. Finally, pericytes were targeted to regulate glial limitan formation, and the effect of the glia limitans on secondary brain injury after SAH was evaluated by flow cytometry and analysis of neurological function. Stress-induced glial limitan formation occurred 1 day after SAH and markedly subsided 3 days after ictus. Pericytes regulated astrocyte glia limitan formation via EphA4/EphrinB2 signaling, inhibited inflammatory cell infiltration and altered neurological function. Astrocyte-derived glia limitans serve as a secondary protective barrier following BBB disruption after SAH in mice, and pericytes can regulate glial limitan formation and alter neurological function via EphA4/EphrinB2 signaling. Strategies for maintaining this secondary protective barrier may be novel treatment approaches for alleviating early brain injury after SAH. [Display omitted] • Glia limitans formation is present 1 day after SAH and subsided then. • Interaction between pericytes and astrocytes via the EphA4/ephrinB2 signal. • EphA4/ephrinB2 interactions can regulate glia limitans formation. • Glia limitans blocks inflammatory cell infiltration after SAH. [ABSTRACT FROM AUTHOR]

Background: Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear. Methods: Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids. Results: Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway. Conclusions: CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH. [ABSTRACT FROM AUTHOR]

Background: Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood–brain barrier dysfunction and vasogenic brain edema. However, there is a few days between blood‒brain barrier dysfunction and vasogenic brain edema. The present study sought to investigate whether this phenomenon is caused by endothelial injury induced by the acute astrocytic barrier, also known as the glial limitans. Methods: Bioinformatics analyses of human endothelial cells and astrocytes under hypoxia were performed based on the GEO database. Wild-type, EGLN3 and PKM2 conditional knock-in mice were used to confirm glial limitan formation after SAH. Then, the effect of endothelial EGLN3-PKM2 signaling on temporal and spatial changes in glial limitans was evaluated in both in vivo and in vitro models of SAH. Results: The data indicate that in the acute phase after SAH, astrocytes can form a temporary protective barrier, the glia limitans, around blood vessels that helps maintain barrier function and improve neurological prognosis. Molecular docking studies have shown that endothelial cells and astrocytes can promote glial limitans-based protection against early brain injury through EGLN3/PKM2 signaling and further activation of the PKC/ERK/MAPK signaling pathway in astrocytes after SAH. Conclusion: Improving the ability to maintain glial limitans may be a new therapeutic strategy for improving the prognosis of SAH patients. [ABSTRACT FROM AUTHOR]

Background: Hydrocephalus is a severe complication of intracerebral hemorrhage with ventricular extension (ICH-IVH) and causes cerebrospinal fluid (CSF) accumulation. The choroid plexus epithelium plays an important role in CSF secretion and constitutes the blood-CSF barrier within the brain-immune system interface. Although the NLRP3 inflammasome, as a key component of the innate immune system, promotes neuroinflammation, its role in the pathogenesis of hydrocephalus after hemorrhage has not been investigated. Therefore, this study aimed to investigate the potential mechanism of NLRP3 in hydrocephalus to discover a potential marker for targeted therapy.Methods: A rat model of hydrocephalus after ICH-IVH was developed through autologous blood infusion in wild-type and Nlrp3-/- rats. By studying the features and processes of the model, we investigated the relationship between the NLRP3 inflammasome and CSF hypersecretion in the choroid plexus.Results: The ICH-IVH model rats showed ventricular dilation accompanied by CSF hypersecretion for 3 days. Based on the choroid plexus RNA-seq and proteomics results, we found that an inflammatory response was activated. The NLRP3 inflammasome was investigated, and the expression levels of NLRP3 inflammasome components reached a peak at 3 days after ICH-IVH. Inhibition of NLRP3 by an MCC950 inflammasome inhibitor or Nlrp3 knockout decreased CSF secretion and ventricular dilation and attenuated neurological deficits after ICH-IVH. The mechanism underlying the neuroprotective effects of NLRP3 inhibition involved decreased phosphorylation of NKCC1, which is a major protein that regulates CSF secretion by altering Na+- and K+-coupled water transport, via MCC950 or Nlrp3 knockout. In combination with the in vitro experiments, this experiment confirmed the involvement of the NLRP3/p-NKCC1 pathway and Na+ and K+ flux.Conclusions: This study demonstrates that NKCC1 phosphorylation in the choroid plexus epithelium promotes NLRP3 inflammasome-mediated CSF hypersecretion and that NLRP3 plays an important role in the pathogenesis of hydrocephalus after hemorrhage. These findings provide a new therapeutic strategy for treating hydrocephalus. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a malignant tumor leading cancer-associated high mortality worldwide. Unfortunately, the most commonly used drug therapeutics not only lack of target ability and efficiency, but also exhibit severe systemic toxicity to normal tissues. Thus, effective and targeted nanodrug of HCC therapy is emerging as a more important issue. Here, we design and develop the novel nanomicelles, namely Mannose-polyethylene glycol 600-Nitroimidazole (Man-NIT). This micelle compound with high purity comprise two parts, which can self-assemble into nanoscale micelle. The outer shell is selected mannose as hydrophilic moiety, while the inner core is nitroimidazole as hydrophobic moiety. In the cell experiment, Man-NIT was more cellular uptake by HCCLM3 cells due to the mannose modification. Mannose as a kind of glucose transporter 1 (GLUT1) substrate, can specifically recognize and bind to over-expressed GLUT1 on carcinoma cytomembrane. The nitroimidazole moiety of Man-NIT was reduced by the over-expressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient deletion of NADPH and glutathione (GSH). The increase of reactive oxygen species (ROS) in HCCLM3 cells disturbed the balance of redox, and finally caused the death of tumor cells. Additional in vivo experiment was conducted using twenty-four male BALB/c nude mice to build the tumor model. The results showed that nanomicelles were accumulated in the liver of mice. The tumor size and pathological features were obviously improved after nanomicelles treatment. It indicates that namomicelles have a tumor inhibition effect, especially Man-NIT, which may be a potential nanodrug of chemotherapeutics for HCC therapy. [ABSTRACT FROM AUTHOR]

Every year vast quantities of silver are lost in various waste streams; this, combined with its limited, diminishing supply and rising demand, makes silver recovery of increasing importance. Thus, herein, we report a controllable, green process to produce a host of highly porous metal–organic framework (MOF)/oligomer composites using supercritical carbon dioxide (ScCO2) as a medium. One resulting composite, referred to as MIL‐127/Poly‐o‐phenylenediamine (PoPD), has an excellent Ag+ adsorption capacity, removal efficiency (>99 %) and provides rapid Ag+ extraction in as little as 5 min from complex liquid matrices. Notably, the composite can also reduce sliver concentrations below the levels (<0.1 ppm) established by the United States Environmental Protection Agency. Using theoretical simulations, we find that there are spatially ordered polymeric units inside the MOF that promote the complexation of Ag+ over other common competing ions. Moreover, the oligomer is able to reduce silver to its metallic state, also providing antibacterial properties. [ABSTRACT FROM AUTHOR]

Every year vast quantities of silver are lost in various waste streams; this, combined with its limited, diminishing supply and rising demand, makes silver recovery of increasing importance. Thus, herein, we report a controllable, green process to produce a host of highly porous metal–organic framework (MOF)/oligomer composites using supercritical carbon dioxide (ScCO2) as a medium. One resulting composite, referred to as MIL‐127/Poly‐o‐phenylenediamine (PoPD), has an excellent Ag+ adsorption capacity, removal efficiency (>99 %) and provides rapid Ag+ extraction in as little as 5 min from complex liquid matrices. Notably, the composite can also reduce sliver concentrations below the levels (<0.1 ppm) established by the United States Environmental Protection Agency. Using theoretical simulations, we find that there are spatially ordered polymeric units inside the MOF that promote the complexation of Ag+ over other common competing ions. Moreover, the oligomer is able to reduce silver to its metallic state, also providing antibacterial properties. [ABSTRACT FROM AUTHOR]

• Tolvaptan attenuated brain edema after intracerebral hemorrhage. • Tolvaptan alleviated neurological deficits after intracerebral hemorrhage. • Tolvaptan prevented blood brain barrier destruction after intracerebral hemorrhage. Arginine-vasopressin (AVP) is believed to be positively correlated with the brain edema formation, but the underlying mechanism is still unclear. In this study, we explored the role of the V2 receptors antagonist tolvaptan on brain edema following intracerebral hemorrhage (ICH) with a rat model. Animals were randomly given tolvaptan or vehicle through oral gavage at 12 h, 36 h, and 60 h after ICH surgery. Brain swelling (%), brain water content(BWC), neurological scores, Evans blue fluorescence and blood-brain barrier (BBB) tight junction proteins were measured to evaluate the effect of tolvaptan in ICH. We found that tolvaptan alleviated the brain swelling (%), decreased the BWC growth, and attenuated the neurological deficits after ICH (p < 0.05, vs vehicle). What's more, tolvaptan increased the expression of ZO-1 and occludin (p < 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9. These results provided evidence supporting the use of tolvaptan for ICH-induced brain edema. Large animal experiments are required to further explore the efficacy and mechanism of tolvaptan in ICH treatment. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) exerts its protective role in a variety of neurological diseases, but the related mechanisms of H2S in autism spectrum disorder (ASD) remain unclear. Toward a better understanding of the physiological role of H2S in ASD patients and mice, we designed a novel H2S detection fluorescent nanoprobe DNS-Az-M by encapsulating DNS-Az into an amphiphilic block copolymer DSPE-PEG2000. DNS-Az-M not only disperses well in aqueous solution and exhibits non-toxicity, but also achieves quantitative detection of H2S contents in biological samples of ASD patients and mice. We first found that the plasma H2S concentration in children with ASD was 12.14 ± 5.03 μM through DNS-Az-M detection, which is remarkably lower than that in children without ASD (17.08 ± 5.85 μM). The same phenomenon was observed in the ASD model BTBR mice. Furthermore, western blot and RT-PCR examination of BTBR mice hippocampus clearly revealed that CBS protein and CBS mRNA, as a key enzyme for H2S synthesis, had lower expression than that of B6 mice. This research provides a basis for the pathogenesis of ASD and outlines a promising strategy for targeted treatment of ASD. [ABSTRACT FROM AUTHOR]

The mesoporous poly(N , N ′-methylene-bis(1-(3-vinylimidazolium)) chloride), labeled as PDVIm-Cl, with double anions (Cl−) and low monomer molecular weight was synthesized and applied in the adsorption of anionic dyes (acid orange 7 (AO7), sunset yellow (SY), reactive blue 19 (RB19), congo red (CR)). Due to the mesoporous structure, abundant Cl− and positively charged imidazole rings, the poly(ionic liquid) (PIL) exhibited superior adsorption ability towards anionic dyes. What is more, the RB19 adsorption by PDVIm-Cl could achieve the highest capacity (2605 ± 254 mg g−1) which was nearly twice higher than the maximum adsorption capacity of the previously reported materials. All the adsorption kinetic data and isotherms fitted well with the pseudo second-order model and Langmuir-Freundlich model. To better explore the practical potential of the PIL for dye adsorption, the adsorption under different pH values and column adsorption performances were also evaluated. Results showed that PDVIm-Cl exhibited high removal efficiencies for anionic dyes over a wide pH range (2−10). Also, the great reusability could be well demonstrated by the achievable continuous column adsorption-desorption process. It is worth mentioning that the regeneration could be realized with very little desorbent which was far less than the adsorption volume flowing through the column and the desorption efficiency was well maintained after three consecutive cycles. At last, the adsorption mechanism was explored by experiments combined with quantum chemical calculations and showed anionic dyes adsorption by PDVIm-Cl was a joint process dominated by the ion exchange, electrostatic interaction, hydrogen bond and π-π stacking. • PDVIm-Cl is capable to adsorb various anionic dyes with high capacities. • PDVIm-Cl shows unprecedented adsorption capacity of 2605 ± 254 mg g−1 for RB19 dye. • PDVIm-Cl could be used to adsorb different anionic dyes in a wide range of pH. • PDVIm-Cl can easily realize continuous column adsorption-desorption process. • The adsorption mechanism is studied by experimental and theoretical calculations. [ABSTRACT FROM AUTHOR]