Antielectric Potential Synthesis of Plasmonic Au-Ag Multidimensional Dimers Array for High-Resolution Encrypted Information.

Plasmonic superstructures hold great potential in encrypted information chips but are still unsatisfactory in terms of resolution and maneuverability because of the limited fabrication strategies. Here, we develop an antielectric potential method in which the interfacial energy from the modification of 5-amino-2-mercapto benzimidazole (AMBI) ligand is used to overcome the electric resistance between the Au nanospheres (NSs) and substrate, thereby realizing the in situ growth of a Au-Ag heterodimers array in large scale. The morphology, number, and size of Ag domains on Au units can be controlled well by modulating the reaction kinetics and thermodynamics. Experiments and theoretical simulations reveal that patterned 3D Au-2D Ag and 3D Au-3D Ag dimer arrays with line widths of 400 nm exhibit cerulean and cyan colors, respectively, and achieve fine color modulation and ultrahigh information resolution. This work not only develops a facile strategy for fabricating patterned plasmonic superstructures but also pushes the plasmon-based high-resolution encrypted information chip into more complex applications.

Peripheral inflammation in behavioural variant frontotemporal dementia: associations with central degeneration and clinical measures.

BACKGROUND: Neuroinflammation plays a significant role in the progression of frontotemporal dementia (FTD). However, the association between peripheral inflammatory factors and brain neurodegeneration is poorly understood. We aimed to examine changes in peripheral inflammatory markers in patients with behavioural variant FTD (bvFTD) and explore the potential association between peripheral inflammation and brain structure, metabolism, and clinical parameters. METHODS: Thirty-nine bvFTD patients and 40 healthy controls were enrolled and underwent assessment of plasma inflammatory factors, positron emission tomography/magnetic resonance imaging, and neuropsychological assessments. Group differences were tested using Student's t test, Mann‒Whitney U test, or ANOVA. Partial correlation analysis and multivariable regression analysis were implemented using age and sex as covariates to explore the association between peripheral inflammatory markers, neuroimaging, and clinical measures. The false discovery rate was used to correct for the multiple correlation test. RESULTS: Plasma levels of six factors, including interleukin (IL)-2, IL-12p70, IL-17A, tumour necrosis superfamily member 13B (TNFSF/BAFF), TNFSF12 (TWEAK), and TNFRSF8 (sCD30), were increased in the bvFTD group. Five factors were significantly associated with central degeneration, including IL-2, IL-12p70, IL-17A, sCD30/TNFRSF8, and tumour necrosis factor (TNF)-α; the association between inflammation and brain atrophy was mainly distributed in frontal-limbic-striatal brain regions, whereas the association with brain metabolism was mainly in the frontal-temporal-limbic-striatal regions. BAFF/TNFSF13B, IL-4, IL-6, IL-17A and TNF-α were found to correlate with clinical measures. CONCLUSION: Peripheral inflammation disturbance in patients with bvFTD participates in disease-specific pathophysiological mechanisms, which could be a promising target for diagnosis, treatment, and monitoring therapeutic efficacy.

Parental marital status and anxiety symptoms in adolescents: the mediating effect of childhood maltreatment.

Although previous studies have established the association between parental marital status and mental health problems in adolescents, however, the adverse effects of incomplete family settings and childhood maltreatment on adolescent anxiety symptoms have not been fully investigated. Moreover, whether childhood maltreatment can mediate the relationship between parental marital status and anxiety symptoms remains unclear. A population-based cross-sectional study was performed among 35,573 adolescents in elementary schools across 17 provinces in China. And childhood maltreatment, resilience, and anxiety symptoms were assessed among adolescents, respectively. The parental marital status was self-reported as having two married biological parents, divorced parents, stepparents, and single-parent. We found that the rates of anxiety symptoms among adolescents were 35.1% in intact families, 48.8% in divorced families, 49% in stepparent families, and 48% in single-parent families. Divorced parents (aOR = 1.191, 95% CI [1.060-1.337]) was an independent risk factor for adolescents' anxiety symptom while having stepparents and single-parent were not. In addition, emotional abuse (aOR = 1.300, 95% CI [1.285-1.316]), sexual abuse (aOR = 1.088, 95% CI [1.063-1.114]), and physical neglect (aOR = 1.019, 95% CI [1.007-1.031]) were all independent risk factors for anxiety symptoms in adolescents, while physical abuse and emotional neglect were not. The negative impacts of divorced and remarried parents on adolescent anxiety symptoms were mediated by childhood maltreatment partially (64.9% and 72.2%), while childhood maltreatment completely mediated the adverse impacts of single-parent on adolescent anxiety symptoms. Childhood maltreatment intervention strategies could be necessary for anxiety symptoms of adolescents in divorced/stepparent/single-parent families.

Vinpocetine Attenuates Ischemic Stroke Through Inhibiting NLRP3 Inflammasome Expression in Mice.

ABSTRACT: Ischemic stroke is the leading cause of globe death and permanent disability, but its therapeutic strategies are limited. Over the past decades, multiprotein complexes called inflammasomes have been shown as promising targets in ischemic stroke. Here, we examined vinpocetine (Vinp), a synthetic drug, playing a neuroprotective role against ischemic stroke in mice through regulating NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation. Middle cerebral artery occlusion/reperfusion (MCAO/R) was applied to mimic ischemic stroke in vivo. Vinp was administrated by intraperitoneal injection with different dose (5 or 10 mg/kg) 1 hour after reperfusion. Then, neurological assessment and infarct size were performed, and interleukin-1ß (IL-1ß) and IL-18 levels were evaluated using ELISA. The levels of NLRP3 inflammasome components and its upstream nuclear factor-κB (NF-κB) were determined using real-time PCR or Western blot. The experimental results indicated that posttreatment with Vinp decreased cerebral infarct size, improved behavior recover, reduced NLRP3 inflammasome expression, and suppressed the transfer of NF-κB to nucleus and proinflammatory cytokine release in middle cerebral artery occlusion/reperfusion mice. In conclusion, this study demonstrates that Vinp alleviates ischemic stroke by regulating levels of NLRP3 inflammasome, NF-κB, and proinflammatory cytokines in vivo, offering an alternative medication for ischemic stroke associated with inflammation.

Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF-2.

Mesenchymal stem cells (MSCs) transplantation has emerged as a potential therapeutic approach for Alzheimer's disease (AD). However, the poor proliferation capacity and low survival rate of engrafted MSCs in the hostile microenvironment of AD limit their therapeutic efficiency. Lin28B is a conserved RNA-binding protein associated with cell self-renewal and survival. The purpose of the present study was to explore whether lin28B might influence the functions of implanted MSCs and strengthen their neuroprotective potential in AD. A gain-of-function assay was used to upregulate lin28B expression in MSCs by lentiviral transfection. Our in vitro results indicated that lin28B promoted MSCs proliferation and migration, and protected MSCs against Aß1-42-induced cell death by upregulating insulin-like growth factor-2 (IGF-2). Blockage of IGF-2 partially abrogated the above effects of lin28B. After intracerebroventricular injection into amyloid precursor protein/presenilin 1 mice, implanted MSCs were monitored using bioluminescence imaging. We observed that administration of MSCs transfected with lin28B significantly stimulated their proliferation and prolonged cell retention after delivery. Moreover, administration of the transfected MSCs markedly mitigated cognitive deficits, promoted amyloid plaque clearance, decreased the activation of microglia, and reduced neuronal cell death. The data above confirmed our hypothesis that lin28B is a crucial modulator determining the fate of transplanted MSCs by regulating IGF-2-associated pathways and thereby enhancing their protective effects against AD.

Cr-Dopant Induced Breaking of Scaling Relations in CoFe Layered Double Hydroxides for Improvement of Oxygen Evolution Reaction.

Monodentate adsorption of oxygen intermediates results in a theoretical overpotential limit of ≈0.35 V for oxygen evolution reaction (OER), which causes the sluggish kinetics of the OER process. In this work, nonprecious chromium dopant is introduced into the self-supported CoFe layered double hydroxides (LDHs) on nickel foam (Cr-CoFe LDHs/NF) via a facile one-step hydrothermal method, which exhibits a preeminent electrocatalytic activity toward the OER with an ultralow overpotential of 238 mV to obtain 10 mA cm-2 and a high stability after cyclic voltammetry for 5000 cycles in alkaline solution (1 m KOH). Density functional theory (DFT) calculations unveil that Cr dopants as new active sites could improve the electron-donation ability of the resultant Cr-CoFe LDHs due to the smaller electronegativity of Cr in comparison with Fe and Co. Therefore, the scaling relation of adsorption energy among four oxygen intermediates is broken and consequently the OER performance is further promoted. This work provides a strategy to develop efficient metal layered double hydroxide OER catalysts.

MnMoO4 nanosheet array: an efficient electrocatalyst for hydrogen evolution reaction with enhanced activity over a wide pH range.

We report the preparation of MnMoO4 nanosheet array on nickel foam (MnMoO4 NSA/NF) as an excellent 3D hydrogen evolution reaction (HER) electrocatalyst with good catalytic performance applied under basic, acidic and neutral conditions. In 0.5 M H2SO4, this MnMoO4 NSA/NF electrode needs an overpotential of 89 mV to drive current densities of 10 mA cm-2, to achieve the same current density, it demands overpotentials of 105 mV in 1.0 M KOH, 161 mV in 1.0 M PBS (pH = 7), respectively. After continuous CV scanning for 1000 cycles under different pH conditions, it also demonstrates an excellent stability with ignorable activity decrease. Such preeminent HER performance may be derived from the synergistic effect between manganese (Mn) and molybdenum (Mo) atoms, exposure of more active sites on the nanosheets and effective electron transport along the nanosheets. This MnMoO4 NSA/NF electrocatalyst provides us a highly efficient material for water splitting devices for industrial hydrogen production.

Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway.

CONTEXT: Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities. OBJECTIVE: The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats. MATERIALS AND METHODS: Seven-day-old pups (n = 48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N2 and 8% O2) for 2.5 h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20 + HI) or 40 mg/kg (RESV 40 + HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7 days prior to HI induction. RESULTS: Pre-treatment with RESV (20 or 40) markedly reduced (p < 0.01) the cerebral oedema (86.23-71.26 or 65.24%), infarct area (33.85-19.81 or 14.30%), lipid peroxidation products, inflammatory markers [IL-1ß 186-110 or 82; IL-6 255-146 or 103; TNF-α 310-204 or 137; NF-κB 205-115 or 91) p65 subunit] and significantly restored (p < 0.01) the antioxidative status by enhancing the activities of glutathione peroxidase (GPx) 5.22-6.49 or 7.78; catalase (CAT) 51-55 or 59, superoxide dismutase (SOD) 2.5-3.05 or 3.25; through marked upregulation (p < 0.01) of heme oxygenase 1 (HO-1) 0.65-0.69 or 0.73; and nuclear factor erythroid 2 related factor 2 (Nrf2) 0.73-0.86 or 0.91. DISCUSSION AND CONCLUSIONS: RESV displays its neurotherapeutic potential via upregulating the protein expression of Nrf2 and HO-1 signalling pathway and thereby attenuates oxidative stress and inflammatory response in HI-induced neonatal rats.

The predictive role of early inflammation and oxidative stress and the dynamics of cytokines networks in post-stroke depression.

BACKGROUNDS: Chronic inflammation and oxidative stress play an important role in the pathogenesis of PSD. The main purposes of this study were to examine the dynamic changes of cytokines networks in PSD and the predictive role of early inflammation and oxidative stress for 2-week PSD. METHODS: Patients with ischemic stroke were recruited on day 3, and those with Hamilton Depression Rating Scale 24-Item (HAMD-24) ≥8 were classified as ischemic stroke patients with depressive symptoms and others as ischemic stroke patients without depressive symptoms. Subjects were then followed up at 2 weeks and 3 months, with those meeting diagnostic criteria for depressive symptoms on the HAMD ≥8 and the Statistical Manual of Mental Disorders-V (DSM-V) as the PSD group, and the others as the non-PSD group. RESULTS: At 3 days, IFN-γ, IL-12(p70), IL-12(p40), IL-2, IL-28A/IFNλ2, and IL-19 were elevated in ischemic stroke patients with depressive symptoms. At 2 weeks, IL-12(p40), IL-19, IL-22, IFN-ß and MMP-1 all were increased in PSD patients. At 3 months, IL-2, IFN-ß and sCD163 increased in PSD group. Longitudinally, the inflammatory response decreased significantly in PSD group from 2 weeks to 3 months of follow-up, while it gradually decreased in non-PSD group from 3 days to 3 months of follow-up. SOD was positively related to IL-12(p70), IFN-γ and IL-20. Plasma IFN-γ at 3 days may be a potential predictive biomarker for 2-week PSD. CONCLUSIONS: Peripheral inflammation and oxidative stress are involved in the pathogenesis of PSD, providing new insights for its diagnosis and treatment.

Vascular dysfunction in sporadic bvFTD: white matter hyperintensity and peripheral vascular biomarkers.

BACKGROUND: Vascular dysfunction was recently reported to be involved in the pathophysiological process of neurodegenerative diseases, but its role in sporadic behavioral variant frontotemporal dementia (bvFTD) remains unclear. The aim of this study was to systematically explore vascular dysfunction, including changes in white matter hyperintensities (WMHs) and peripheral vascular markers in bvFTD. METHODS: Thirty-two patients with bvFTD who with no vascular risk factors were enrolled in this cross-sectional study and assessed using positron emission tomography/magnetic resonance (PET/MRI) imaging, peripheral plasma vascular/inflammation markers, and neuropsychological examinations. Group differences were tested using Student's t-tests and Mann-Whitney U tests. A partial correlation analysis was implemented to explore the association between peripheral vascular markers, neuroimaging, and clinical measures. RESULTS: WMH was mainly distributed in anterior brain regions. All peripheral vascular factors including matrix metalloproteinases-1 (MMP-1), MMP-3, osteopontin, and pentraxin-3 were increased in the bvFTD group. WMH was associated with the peripheral vascular factor pentraxin-3. The plasma level of MMP-1 was negatively correlated with the gray matter metabolism of the frontal, temporal, insula, and basal ganglia brain regions. The WMHs in the frontal and limbic lobes were associated with plasma inflammation markers, disease severity, executive function, and behavior abnormality. Peripheral vascular markers were associated with the plasma inflammation markers. CONCLUSIONS: WMHs and abnormalities in peripheral vascular markers were found in patients with bvFTD. These were found to be associated with the disease-specific pattern of neurodegeneration, indicating that vascular dysfunction may be involved in the pathogenesis of bvFTD. This warrants further confirmation by postmortem autopsy. Targeting the vascular pathway might be a promising approach for potential therapy.

Lipid metabolism and oxidative stress in patients with Alzheimer's disease and amnestic mild cognitive impairment.

Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non-targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC-MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)-CH3, and PE (20:0_20:4)-H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high-performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group (p = 0.003), whereas plasma SOD levels were lower in the AD (p < 0.001) and aMCI (p = 0.045) groups than in NC, and GSH-Px activity were higher in the AD group than in the aMCI group (p = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress.

The mediating role of childhood maltreatment in the association between residence migration and adolescent depression.

BACKGROUND: It is well established that residence migration can negatively affect the mental health of adolescents. However, the related factors that mediate the association between residence migration and depression are still uncertain. METHODS: The participants were 16,037 adolescents in junior middle schools. A self-administered questionnaire was used for the survey. In addition to collecting general demographic characteristics of the participants, including age, gender, local residence status, only child status, parental marriage status and parent-child relationship, the questionnaire also contained the 9-item Patient Health Questionnaire, the short form of the Childhood Trauma Questionnaire and the Connor-Davidson Resilience Scale. Data analysis was conducted using SPSS software. RESULTS: A total of 14,059 valid questionnaires were collected, resulting in 12,122 local adolescents, defined as being born and raised locally, and 1937 migrant adolescents, defined as being transferred from other regions. Meanwhile, 53.3 % of local adolescents and 58.2 % of migrant adolescents reported depressive symptoms. This result indicated that residence migration might contribute to depression symptoms(OR = 1.136, 95%CI: 1.013-1.273, p < 0.05). Childhood maltreatment and parental divorce are risk factors for depression in migrant adolescents. For all adolescents, resilience and a good parent-child relationship may reduce the risk of depression. Childhood maltreatment completely mediates residence migration-related depression(95 % bootstrap CI = 0.146, 0.323). CONCLUSION: This study revealed that residence migration could contribute to adolescent depression, and childhood maltreatment may largely mediate this process, providing new insight into the relationship between adolescent depressive symptoms and residence migration. Reducing childhood maltreatment may effectively improve the depressive symptoms of migrant adolescents.

Hydrophobic Microenvironment Modulation of Ru Nanoparticles in Metal-Organic Frameworks for Enhanced Electrocatalytic N2 Reduction.

The modulation of the chemical microenvironment surrounding metal nanoparticles (NPs) is an effective means to enhance the selectivity and activity of catalytic reactions. Herein, a post-synthetic modification strategy is developed to modulate the hydrophobic microenvironment of Ru nanoparticles encapsulated in a metal-organic framework (MOF), MIP-206, namely Ru@MIP-Fx (where x represents perfluoroalkyl chain lengths of 3, 5, 7, 11, and 15), in order to systematically explore the effect of the hydrophobic microenvironment on the electrocatalytic activity. The increase of perfluoroalkyl chain length can gradually enhance the hydrophobicity of the catalyst, which effectively suppresses the competitive hydrogen evolution reaction (HER). Moreover, the electrocatalytic production rate of ammonia and the corresponding Faraday efficiency display a volcano-like pattern with increasing hydrophobicity, with Ru@MIP-F7 showing the highest activity. Theoretical calculations and experiments jointly show that modification of perfluoroalkyl chains of different lengths on MIP-206 modulates the electronic state of Ru nanoparticles and reduces the rate-determining step for the formation of the key intermediate of N2H2 *, leading to superior electrocatalytic performance.

Heterogeneity of single small subcortical infarction can be reflected in lesion location.

Single small subcortical infarction (SSSI), also called lacunar infarction, has been regarded as a different entity with distinct pathogenesis, either lipohyalinosis and fibrinoid degeneration or atherosclerosis. The aim of our study is to identify the heterogeneity of SSSI by comparing the characteristics and imaging features according to lesion location. We retrospectively studied 203 patients with acute SSSIs (diameter ≤20 mm) demonstrated by diffusion-weighted imaging in the perforator territory of the middle cerebral artery, basilar artery, or vertebral artery. We divided the 203 patients according to the lesion location in relation to the parent artery into a distal infarction (dSSSI) group and a proximal infarction (pSSSI) group. We evaluated and compared the imaging features and clinical characteristics between the groups. The evaluated characteristics included indicators of lipohyalinosis [leukoaraiosis and silent brain infarction (SBI)], indicators of atherosclerosis [parent artery disease (PAD) and atherosclerosis of other cerebral arteries (AOCA)], lesion size, and some vascular risk factors. Between the two groups, the pSSSI group had larger lesion size, higher prevalence of PAD and AOCA, and greater frequency of diabetes mellitus, while the dSSSI group had smaller lesion size, higher prevalence of leukoaraiosis and SBI, and lower serum folic acid. Diversity of the SSSIs in imaging features and clinical characteristics according to lesion location suggests the heterogeneity of SSSIs; distal infarction is closely associated with lipohyalinosis, while proximal infarction seems to be related with atherosclerosis.

Metabolic Alterations and Related Biological Functions of Post-Stroke Depression in Ischemic Stroke Patients.

Background: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. However, the underlying mechanisms of PSD remain ambiguous, and no objective diagnosis tool is available to diagnose PSD. Previous metabolomic studies on PSD included patients with ischemic and hemorrhagic stroke indiscriminately, which is not conducive to elucidating and predicting the occurrence of PSD. The aim of this study is to elucidate the pathogenesis of PSD and provide potential diagnostic markers for PSD in ischemic stroke patients. Methods: In total, 51 ischemic stroke patients at 2 weeks were included in this study. Those with depressive symptoms were assigned to the PSD group, while the others were assigned to the non-PSD group. Plasma metabolomics based on liquid chromatography-mass spectrometry (LC-MS) was performed to explore the differential plasma metabolites between the PSD and non-PSD groups. Results: Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) showed significant metabolic alterations between PSD patients and non-PSD patients. In total, 41 differential metabolites were screened out, mainly including phosphatidylcholines (PCs), L-carnitine and acyl carnitines, succinic acid, pyruvic acid and L-lactic acid. Metabolite-related pathway analysis revealed that alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism and the citrate cycle (TCA cycle) may contribute to the pathogenesis of PSD. A panel of three signature metabolites [PC(22:5(7Z,10Z,13Z,16Z,19Z)/15:0), LysoPA(18:1(9Z)/0:0) and 1,5-anhydrosorbitol] was determined as potential biomarkers for PSD in ischemic stroke patients. Conclusion: These findings are conducive to providing new insights into the pathogenesis of PSD and developing objective diagnostic tools for PSD in ischemic stroke patients.

Associations between resilience and symptoms of depression and anxiety among adolescents: Examining the moderating effects of family environment.

Depressive and anxiety symptoms in adolescents have experienced increase their risk of peripheral mental health and social problems. For adolescents, the role of family environmental factors should be taken into consideration. This study aimed to explore the association between resilience and depressive and anxiety symptoms in adolescents and to extend the findings by examining the moderating effects of family environment. A total of 35,573 adolescents in middle schools were recruited in China. Childhood abuse, resilience, and symptoms of depression and anxiety were evaluated in adolescents. We found a significant association between resilience and symptoms of depression and anxiety [OR = 0.976 (0.975-0.978), P < 0.001; OR = 0.980 (0.978-0.981), P < 0.001]. The adjusted ORs (95 % CIs) for mental health across the categories of resilience were as follows: 1 (reference) for low resilience, 0.660 (0.620-0.703) for medium resilience, 0.309 (0.286-0.333) for high resilience. The relationship between resilience and depressive symptoms was stronger for girls, non-only children, and those without child abuse experience compared to boys, only child, and those with child abuse experience (all p < 0.05). Our findings of a nationally representative sample in China suggest that gender, only child, parent-child relationship and child abuse moderated the relationship between resilience and symptoms of depression and anxiety.

Metabolic reprogramming and polarization of microglia in Parkinson's disease: Role of inflammasome and iron.

Parkinson's disease (PD) is a slowly progressive neurodegenerative disease characterized by α-synuclein aggregation and dopaminergic neuronal death. Recent evidence suggests that neuroinflammation is an early event in the pathogenesis of PD. Microglia are resident immune cells in the central nervous system that can be activated into either pro-inflammatory M1 or anti-inflammatory M2 phenotypes as found in peripheral macrophages. To exert their immune functions, microglia respond to various stimuli, resulting in the flexible regulation of their metabolic pathways. Inflammasomes activation in microglia induces metabolic shift from oxidative phosphorylation to glycolysis, and leads to the polarization of microglia to pro-inflammatory M1 phenotype, finally causing neuroinflammation and neurodegeneration. In addition, iron accumulation induces microglia take an inflammatory and glycolytic phenotype. M2 phenotype microglia is more sensitive to ferroptosis, inhibition of which can attenuate neuroinflammation. Therefore, this review highlights the interplay between microglial polarization and metabolic reprogramming of microglia. Moreover, it will interpret how inflammasomes and iron regulate microglial metabolism and phenotypic shifts, which provides a promising therapeutic target to modulate neuroinflammation and neurodegeneration in PD and other neurodegenerative diseases.

Electronic State and Microenvironment Modulation of Metal Nanoparticles Stabilized by MOFs for Boosting Electrocatalytic Nitrogen Reduction.

Modulation of the local electronic structure and microenvironment of catalytic metal sites plays a critical role in electrocatalysis, yet remains a grand challenge. Herein, PdCu nanoparticles with an electron rich state are encapsulated into a sulfonate functionalized metal-organic framework, UiO-66-SO3 H (simply as UiO-S), and their microenvironment is further modulated by coating a hydrophobic polydimethylsiloxane (PDMS) layer, affording PdCu@UiO-S@PDMS. This resultant catalyst presents high activity toward the electrochemical nitrogen reduction reaction (NRR, Faraday efficiency: 13.16%, yield: 20.24 µg h-1 mgcat. -1 ), far superior to the corresponding counterparts. Experimental and theoretical results jointly demonstrate that the protonated and hydrophobic microenvironment supplies protons for the NRR yet suppresses the competitive hydrogen evolution reaction reaction, and electron-rich PdCu sites in PdCu@UiO-S@PDMS are favorable to formation of the N2 H* intermediate and reduce the energy barrier of NRR, thereby accounting for its good performance.

Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson's disease.

Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus. Therefore, using these two treatments may help treat Parkinson's disease. To further investigate the mechanisms of action of these two compounds, we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin. We found that both exendin-4 and linagliptin reversed motor dysfunction, glial activation, and dopaminergic neuronal death in this model. In addition, both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion. Moreover, in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain- and leucine-rich-repeat- and pyrin-domain-containing 3/caspase-1/interleukin-1ß pathway and subsequent pyroptosis by decreasing the production of reactive oxygen species. These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotide-binding oligomerization domain- and leucine-rich-repeat- and pyrin-domain-containing 3/caspase-1/interleukin-1ß pathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Therefore, these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.

Rapid controllable synthesis of branched Au superparticles: formation mechanism of toggling the growth mode and their applications in optical broadband absorption.

We develop a tunable, ultrafast (5 seconds), and mass-producible seed-mediated synthesis method to prepare branched Au superparticles consisting of multiple small Au island-like nanoparticles by a wet chemical route. We reveal and confirm the toggling formation mechanism of Au superparticles between the Frank-van der Merwe (FM) growth mode and the Volmer-Weber (VW) growth mode. The key factor of this special structure is the frequent toggling between the FM (layer by layer) growth mode and the VW (island) growth mode induced by 3-aminophenol, which is continuously absorbed on the surface of newborn Au nanoparticles, leading to a relatively high surface energy during the overall synthesis process, thus achieving an island on island growth. Such Au superparticles demonstrate broadband absorption from visible to near-infrared regions due to their multiple plasmonic coupling and hence they have important applications in sensors, photothermal conversion and therapy, etc. We also exhibit the excellent properties of Au superparticles with different morphologies, such as NIR-II photothermal conversion and therapy and SERS detection. The photothermal conversion efficiency under 1064 nm laser irradiation was calculated to be as high as 62.6% and they exhibit robust photothermal therapy efficiency. This work provides insight into the growth mechanism of plasmonic superparticles and develops a broadband absorption material for highly efficient optical applications.