Spontaneous Formation of Highly Stable Nanoparticle Supercrystals Driven by a Covalent Bonding Interaction.

Nanoparticle supercrystals (NPSCs) are of great interest as materials with emergent properties. Different types of intermolecular forces, such as van der Waals interaction and hydrogen bonding, are present in the NPSCs fabricated to date. However, the limited structural stability of such NPSCs that results from the weakness of these intermolecular forces is a challenge. Here, we report a spontaneous formation of NPSCs driven by covalent bonding interactions, a type of intramolecular force much stronger than the above-mentioned intermolecular forces. A model solution-phase anhydride reaction is used to form covalent bonds between molecules grafted on the surface of gold nanoparticles, resulting in three-dimensional NPSCs. The NPSCs are very stable in different solvents, in dried conditions, and at temperatures as high as 160 °C. In addition to this, the large library of covalent-bond-forming reactions available and the low cost of reactants make the covalent bonding approach highly versatile and economical.

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.

Micelle-Assisted Formation of Nanoparticle Superlattices and Thermally Reversible Symmetry Transitions.

Nanoparticle superlattices (NPSLs) are of great interest as materials with designed emerging properties depending on the lattice symmetry as well as composition. The symmetry transition of NPSLs depending on environmental conditions can be an excellent ground for making new stimuli-responsive functional materials. Here, we report a spherical micelle-assisted method to form exceptionally ordered NPSLs which are inherently sensitive to environmental conditions. Upon mixing functionalized gold nanoparticles (AuNPs) with a nonionic surfactant spherical micellar solution, NPSLs of different symmetries such as NaZn13, MgZn2, and AlB2-type are formed depending on the size ratio between micelles and functionalized AuNPs and composition. The NPSLs formed by the spherical micelle-assisted method show thermally reversible order-order (NaZn13-AlB2) and order-disorder (MgZn2-isotropic) symmetry transitions, which are consistent with the Gibbs free energy calculations for binary hard-sphere model. This approach may open up new possibilities for NPSLs as stimuli-responsive functional materials.

Green Synthesis of High-Purity Mesoporous Gold Sponges Using Self-Assembly of Gold Nanoparticles Induced by Thiolated Poly(ethylene glycol).

A facile and green synthesis method for mesoporous gold sponges has been developed, which involves a simple mixing of a very small amount of thiolated-poly(ethylene glycol) (SH-PEG) and citrate-covered gold nanoparticles (Au NPs) in aqueous solution at room temperature. While SH-PEG molecules have been widely used as biocompatible hydrophilic capping agents for Au NPs for stable dispersion in aqueous solution, here they are used as destabilizing agents. When SH-PEG molecules are mixed with citrate-covered Au NPs at the molar ratio ranging from 3 to 20 (SH-PEG/Au NP), mesoporous gold sponges with randomly interconnected 3D network structures are formed within 2 to 3 h. This is driven by the destabilization of negatively charged citrate molecules on Au NPs by a small number of SH-PEG molecules bonded on the particle surface, which results in the decrease in zeta potential and thus the assembly of Au NPs into porous sponges. The use of very low concentration of SH-PEG (ca. 20-200 nM) in aqueous solution at room temperature makes the method highly eco-friendly as well as results in high-purity as-synthesized gold sponges (98.7 wt %). The mesoporous gold sponges fabricated with the present method exhibit a high SERS activity, making them highly applicable for sensitive SERS detection of molecules.

Selective distributions of functionalized single-walled carbon nanotubes in a polymeric reverse hexagonal phase.

We have investigated the distributions of individually isolated and hydrophilically functionalized single-walled carbon nanotubes (p-SWNTs) in the Pluronic L121-water system at the reverse hexagonal phase using small-angle X-ray scattering (SAXS) and contrast-matched small-angle neutron scattering (SANS) measurements. As the p-SWNT-L121-water system is transitioned from the lamellar phase to the reverse hexagonal phase with temperature, p-SWNTs which were selectively distributed in the polar layers of the lamellar structure become selectively distributed in the cylindrical polar cores of the reverse hexagonal structure, forming a hexagonal array of p-SWNTs. This was clearly confirmed by the contrast-matched SANS measurements. The selective distribution of p-SWNTs in the reverse hexagonal phase is driven by the selective affinity of p-SWNTs to the polar domains of the block copolymer system. The method demonstrated in this study provides a new route for fabricating ordered SWNT superstructures and may be applicable for inorganic 1D nanoparticles such as semiconducting, metallic and magnetic nanorods which are of great interest.

Highly ordered and highly aligned two-dimensional binary superlattice of a SWNT/cylindrical-micellar system.

We report a highly ordered intercalated hexagonal binary superlattice of hydrophilically functionalized single-walled carbon nanotubes (p-SWNTs) and surfactant (C12 E5 ) cylindrical micelles. When p-SWNTs (with a diameter slightly larger than that of the C12 E5 cylinders) were added to the hexagonally packed C12 E5 cylindrical-micellar system, p-SWNTs positioned themselves in such a way that the free-volume entropies for both p-SWNTs and C12 E5 cylinders were maximized, thus resulting in the intercalated hexagonal binary superlattice. In this binary superlattice, a hexagonal array of p-SWNTs is embedded in a honeycomb lattice of C12 E5 cylinders. The intercalated hexagonal binary superlattice can be highly aligned in one direction by an oscillatory shear field and remains aligned after the shear is removed.

Nanoparticle Superlattices Driven by Linker-Mediated Covalent Bonding Interaction.

The stability of the nanoparticle superlattice (NPSL) is essential for realizing its broad spectrum of potential applications. Here, we report a linker-mediated covalent bonding interaction method for the synthesis of highly stable NPSLs. Adipic acid is used as a linker molecule which connects two Au NPs functionalized with 6-mercaptohexanol through esterification reactions in the presence of H2SO4. As-prepared NPSLs are mostly fcc Wulff polyhedra with a fairly narrow size distribution and are highly stable in solvents of different polarities and pHs (0-14) as well as in dry conditions and at temperatures as high as 175 °C. The formation of NPSLs involves random homogeneous nucleation simultaneously accompanied by growth, a gradual change of the growth mode from reaction-controlled to diffusion-controlled with time, and the oriented attachments of small crystals. The size of the NPSL can be easily tuned by the concentration of linker molecules and the reaction temperature.

Hydration forces between surfaces of surfactant coated single-walled carbon nanotubes.

The interaction force between functionalized single-walled carbon nanotubes (SWNTs) plays an important role in the fabrication of self-assembled and highly ordered SWNT arrays for a wide range of potential applications. Here, we measured interaction force between SWNTs encapsulated with polymerized surfactant monolayer (p-SWNTs). The balance between the repulsion between p-SWNTs and the osmotic pressure exerted by poly(ethylene glycol) in aqueous solution results in two-dimensional hexagonal arrays of p-SWNTs with very small surface to surface distances (<1 nm). The interaction force measured by the osmotic pressure technique shows characteristic decay length of hydration force in its origin.

Effect of the Mandibular Orthopedic Repositioning Appliance on Trunk and Upper Limb Muscle Activation during Maximum Isometric Contraction.

[Purpose] The purpose of this study was to measure the muscle activities of the trunk muscles and upper limb muscles during maximum isometric contraction when temporomandibular joint alignment was achieved with a mandibular orthopedic repositioning appliance in order provide basic data on the effects of mandibular orthopedic repositioning appliance on the entire body. [Subjects] The present study was conducted with healthy Korean adults in their 20s (males=10, females=10). [Methods] An 8 channel surface electromyography system was used to measure the muscle activities of the upper limb muscles and neck muscles of the subjects during maximum isometric contraction with and without use of a mandibular orthopedic repositioning appliance. [Results] The maximum isometric contractions of the trunk and upper limb muscles when mandibular orthopedic repositioning appliance were used were compared with those when no mandibular orthopedic repositioning appliance was used. The results showed that the sternocleidomastoid muscle, cervical and lumbar erector spinae, upper trapezius, biceps, triceps, rectus abdominis and internal oblique and external oblique muscles all showed significant increases in maximum isometric contractions with a mandibular orthopedic repositioning appliance. [Conclusion] The use of a mandibular orthopedic repositioning appliance is considered to be a method for normal adults to improve the stability of the entire body with the improvement of the stability of the TMJ. The proximal improvement in stability improves of the proximal thereby improving not only muscle strength with increased muscle activation but also stability during exercises.

Prevention of severe lung immunopathology associated with influenza infection through adeno-associated virus vector administration.

BACKGROUND: Influenza A viruses (IAVs) have long posed a threat to humans, occasionally causing significant morbidity and mortality. The initial immune response is triggered by infected epithelial cells, alveolar macrophages and dendritic cells. However, an exaggerated innate immune response can result in severe lung injury and even host mortality. One notable pathology observed in hosts succumbing to severe influenza is the excessive influx of neutrophils and monocytes into the lung. In this study, we investigated a strategy for controlling lung immunopathology following severe influenza infection. RESULTS: To evaluate the impact of innate immunity on influenza-associated lung injury, we employed CB17.SCID and NOD.SCID mice. NOD.SCID mice exhibited slower weight loss and longer survival than CB17.SCID mice following influenza infection. Lung inflammation was reduced in NOD.SCID mice compared to CB17.SCID mice. Bulk RNA sequencing analysis of lung tissue showed significant downregulation of 827 genes, and differentially expressed gene analysis indicated that the cytokine-cytokine receptor interaction pathway was predominantly downregulated in NOD.SCID mice. Interestingly, the expression of the Cxcl14 gene was higher in the lungs of influenza-infected NOD.SCID mice than in CB17.SCID mice. Therefore, we induced overexpression of the Cxcl14 gene in the lung using the adeno-associated virus 9 (AAV9)-vector system for target gene delivery. However, when we administered the AAV9 vector carrying the Cxcl14 gene or a control AAV9 vector to BALB/c mice from both groups, the morbidity and mortality rates remained similar. Both groups exhibited lower morbidity and mortality than the naive group that did not receive the AAV9 vector prior to IAV infection, suggesting that the pre-administration of the AAV9 vector conferred protection against lethal influenza infection, irrespective of Cxcl14 overexpression. Furthermore, we found that pre-inoculation of BALB/c mice with AAV9 attenuated the infiltration of trans-macrophages, neutrophils and monocytes in the lungs following IAV infection. Although there was no difference in lung viral titers between the naive group and the AAV9 pre-inoculated group, pre-inoculation with AAV9 conferred lung injury protection against lethal influenza infection in mice. CONCLUSIONS: Our study demonstrated that pre-inoculation with AAV9 prior to IAV infection protected mouse lungs from immunopathology by reducing the recruitment of inflammatory cells.

CD1b glycoprotein, a crucial marker of thymocyte development during T cell maturation in cynomolgus monkeys.

Phenotypic markers that denote different developmental stages of thymocytes are important for understanding T cell development in the thymus. Here, we show that CD1b is a critical discriminator of thymocyte maturation stage in cynomolgus monkeys. CD1b was expressed by immature thymocytes prior to ß-selection, and its expression decreased as cells became fully mature in the thymus. MHC-I expression was lowest at the CD3loCD1b+ immature double-positive (DP) stage, while the ratio of CD1d:MHC-I expression was significantly higher at this stage than at other developmental stages. PLZF was expressed by < 0.2% of thymocytes; most PLZF+ thymocytes were CD3-/loCD1b+ immature DP thymocytes with the potential to produce IL-4. EOMES+ thymocytes, which accounted for > 2% of total thymocytes, were mostly CD3+CD1b- mature thymocytes and predominantly of the CD8 single-positive (SP) lineage. An unconventional CD8+ T cell subset expressing the NKG2AC+CXCR3+ innate-like T cell marker was identified within the EOMES+ CD8 SP lineage; these cells exhibited a memory phenotype. Taken together, these findings show that CD1b is a valuable discriminatory marker of thymocyte development. The data presented herein can be used to characterize the features of PLZF- and EOMES-associated unconventional T cells in the thymus.

IL-4/IL-4 Ab complex enhances the accumulation of both antigen-specific and bystander CD8 T cells in mouse lungs infected with influenza A virus.

BACKGROUND: Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection. RESULTS: In vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3. CONCLUSIONS: These data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.

Attenuated facial movement in depressed women is associated with symptom severity, and nucleus accumbens functional connectivity.

It is assumed that mood can be inferred from one's facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage. The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated. Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus. The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry.

Heterogeneity of circulating CD4+CD8+ double-positive T cells characterized by scRNA-seq analysis and trajectory inference.

The frequency of CD4+CD8+ double-positive (DP) T cells is highly associated with a variety of diseases. Recently, we used high-throughput single-cell RNA sequencing to show that circulating DP T cells in cynomolgus monkeys comprise nine heterogeneous populations. To better understand the characteristics of DP T cells, we analyzed 7601 cells from a rhesus monkey and detected 14,459 genes. Rhesus monkey DP T cells comprised heterogeneous populations (naïve, Treg-, Tfh-, CCR9+ Th-, Th17-, Th2-, Eomes+ Tr1-, CTL-, PLZF+ innate- and Eomes+ innate-like cells) with multiple potential functions. We also identified two new subsets using aggregated scRNA-seq datasets from the rhesus and the cynomolgus monkey: CCR9+ Th-like cells expressing ICAM2 and ITGA1, and PLZF+ innate-like cells that display innate-associated gene signatures such as ZBTB16, TYROBP, MAP3K8, and KLRB1. Trajectory inference of cell differentiation status showed that most DP T cells in the rhesus monkey were found in the mid-to-late pseudotime, whereas DP T cells from the cynomolgus monkey were found in early pseudotime. This suggests that DP T cells in rhesus monkeys may exhibit more diverse differentiation states than those in cynomolgus monkeys. Thus, scRNA-seq and trajectory inference identified a more diverse subset of the circulating DP T cells than originally thought.

Clinical Characteristics of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Korean Children: A Multicenter Retrospective Study.

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Blood cell assisted in vivo Particle Image Velocimetry using the confocal laser scanning microscope.

We demonstrated the feasibility of blood cell assisted in vivo Particle Image Velocimetry using confocal microscopy. Blood flow of skin vessel in a mouse was non-invasively imaged in vivo using a confocal microscopy. The video-rate confocal microscope was used to monitor the motion of the blood cells in the capillary of a live mouse ear. The home-built confocal laser scanning microscopy allowed us to take images at the acquisition rate of 30 frames per second. The individual blood cells could be distinguished from other cells and the trajectory of the each cell could be followed in the sequential images. The acquired confocal images were used to get the velocity profile of the in vivo blood flow in conjunction with the Particle Image Velocimetry (PIV), without injecting any exogenous nano/micro particles into the mouse. We were able to measure the blood velocity up to a few hundreds µm/sec for various vessels in a live mouse. Because there is no need for the injection of the exogenous tracing particles, it is expected that we could apply the current technology to the study of human capillary blood stream.

Comparative finite element analysis of mandibular posterior single zirconia and titanium implants: a 3-dimensional finite element analysis.

PURPOSE: Zirconia has exceptional biocompatibility and good mechanical properties in clinical situations. However, finite element analysis (FEA) studies on the biomechanical stability of two-piece zirconia implant systems are limited. Therefore, the aim of this study was to compare the biomechanical properties of the two-piece zirconia and titanium implants using FEA. MATERIALS AND METHODS: Two groups of finite element (FE) models, the zirconia (Zircon) and titanium (Titan) models, were generated for the exam. Oblique (175 N) and vertical (175 N) loads were applied to the FE model generated for FEA simulation, and the stress levels and distributions were investigated. RESULTS: In oblique loading, von Mises stress values were the highest in the abutment of the Zircon model. The von Mises stress values of the Titan model for the abutment screw and implant fixture were slightly higher than those of the Zircon model. Minimum principal stress in the cortical bone was higher in the Titan model than Zircon model under oblique and vertical loading. Under both vertical and oblique loads, stress concentrations in the implant components and bone occurred in the same area. Because the material itself has high stiffness and elastic modulus, the Zircon model exhibited a higher von Mises stress value in the abutments than the Titan model, but at a level lower than the fracture strength of the material. CONCLUSION: Owing to the good esthetics and stress controllability of the Zircon model, it can be considered for clinical use.

Cellular heterogeneity of circulating CD4+CD8+ double-positive T cells characterized by single-cell RNA sequencing.

Circulating CD4+CD8+ double-positive (DP) T cells are associated with a variety of disease states. However, unlike conventional T cells, the composition of this population is poorly understood. Here, we used single-cell RNA sequencing (scRNA-seq) to analyze the composition and characteristics of the DP T cell population circulating in the peripheral blood of cynomolgus monkeys. We found that circulating DP T cells not only contain a large number of naïve cells, but also comprise a heterogeneous population (CD4 CTL-, Eomes+ Tr1-, Th2-, Th17-, Tfh-, Treg-, CD8 CTL-, and innate-like cells) with multiple potential functions. Flow cytometry analysis revealed that a substantial number of the naïve DP T cells expressed CD8αß, as well as CD8αα, along with high expression of CD31. Moreover, the CD4hiCD8lo and CD4hiCD8hi populations, which express high levels of the CD4 coreceptor, comprised subsets characterized by helper and regulatory functions, some of which also exhibited cytotoxic functions. By contrast, the CD4loCD8hi population with high CD8 coreceptor expression comprised a subset characterized by CD8 CTL- and innate-like properties. Taken together, the data show that scRNA-seq analysis identified a more diverse subset of the circulating DP cells than is currently known, despite this population being very small.

The potential LXRß agonist stigmasterol protects against hypoxia/reoxygenation injury by modulating mitophagy in primary hippocampal neurons.

BACKGROUND: Neuronal excitotoxicity induces a plethora of downstream signaling pathways, resulting in the calcium overload-induced excitotoxic cell death, a well-known phenomenon in cerebrovascular and neurodegenerative disorders. The naturally occurring phytosterol, stigmasterol (ST) is known for its potential role in cholesterol homeostasis and neuronal development. However, the ability of ST to protect against the induced excitotoxicity in hippocampal neurons has not been investigated yet. PURPOSE: The present study aimed to investigate whether ST could protect against hypoxia/reoxygenation (H/R)-induced excitotoxicity in hippocampal neurons. METHODS: After H/R, neurons were initially subjected to trypan blue exclusion assay for the assessment of cell viability. Live staining using fluorescence dyes namely JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide), DCFDA (2',7'-dichlorofluorescein diacetate) and FM1-43 (N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) were used to measure MMP, ROS and synaptic vesicle pool size. Immunostaining was performed to analyze the expression levels of vesicular glutamate transporter 1 (VGLUT1), N-methyl-D-acetate receptor subunit 2B (GluN2B), LC3BII, p62, and PTEN induced protein kinase 1 (PINK1) in neuron after H/R. Western blotting was carried out to measure the protein expression of GluN2B. The molecular dynamics simulation was employed to elucidate the LXRß agonistic conformation of ST. RESULT: Pre-incubation of neuronal cultures with ST (20 µM) protected against excitotoxicity, and attenuated reactive oxygen species (ROS) generation, double-stranded DNA break, and mitochondrial membrane potential (MMP) loss. ST treatment also resulted in the downregulation of the expressions of VGLUT1 and GluN2B and the reduction of the size of recyclable synaptic vesicle (SV) pool. Like LXRß agonist GW3695, ST suppressed the expression of GluN2B. Furthermore, ST induced mitophagy through upregulating the expressions of LC3BII, p62, and PINK1. The molecular simulation study showed that ST interacted with the ligand binding domain of liver X receptor ß (LXRß), a known binding receptor of ST, through multiple hydrogen bonding. CONCLUSION: Collectively, these findings revealed that ST exhibited a promising neuroprotective effect by regulating both pre- and post-synaptic events following H/R, particularly, attenuation of GluN2B-mediated excitotoxicity and oxidative stress, and induction of mitophagy, and suggested that ST might be a therapeutic promise against ischemic stroke and its associated neurological disorders.

Phytosterols: Targeting Neuroinflammation in Neurodegeneration.

Plant-derived sterols, phytosterols, are well known for their cholesterol-lowering activity in serum and their anti-inflammatory activities. Recently, phytosterols have received considerable attention due to their beneficial effects on various non-communicable diseases, and recommended use as daily dietary components. The signaling pathways mediated in the brain by phytosterols have been evaluated, but little is known about their effects on neuroinflammation, and no clinical studies have been undertaken on phytosterols of interest. In this review, we discuss the beneficial roles of phytosterols, including their attenuating effects on inflammation, blood cholesterol levels, and hallmarks of the disease, and their regulatory effects on neuroinflammatory disease pathways. Despite recent advancements made in phytosterol pharmacology, some critical questions remain unanswered. Therefore, we have tried to highlight the potential of phytosterols as viable therapeutics against neuroinflammation and to direct future research with respect to clinical applications.