A Review on Recent Deep Learning-Based Semantic Segmentation for Urban Greenness Measurement.

Accurate urban green space (UGS) measurement has become crucial for landscape analysis. This paper reviews the recent technological breakthroughs in deep learning (DL)-based semantic segmentation, emphasizing efficient landscape analysis, and integrating greenness measurements. It explores quantitative greenness measures applied through semantic segmentation, categorized into the plan view- and the perspective view-based methods, like the Land Class Classification (LCC) with green objects and the Green View Index (GVI) based on street photographs. This review navigates from traditional to modern DL-based semantic segmentation models, illuminating the evolution of the urban greenness measures and segmentation tasks for advanced landscape analysis. It also presents the typical performance metrics and explores public datasets for constructing these measures. The results show that accurate (semantic) segmentation is inevitable not only for fine-grained greenness measures but also for the qualitative evaluation of landscape analyses for planning amidst the incomplete explainability of the DL model. Also, the unsupervised domain adaptation (UDA) in aerial images is addressed to overcome the scale changes and lack of labeled data for fine-grained greenness measures. This review contributes to helping researchers understand the recent breakthroughs in DL-based segmentation technology for challenging topics in UGS research.

Angiotensin-converting enzyme inhibition prevents l-dopa-induced dyskinesia in a 6-ohda-induced mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin-angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44, and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD.

Agathobaculum butyriciproducens improves ageing-associated cognitive impairment in mice.

AIMS: The gut microbiota is increasingly recognised as a pivotal regulator of immune system homeostasis and brain health. Recent research has implicated the gut microbiota in age-related cognitive impairment and dementia. Agathobaculum butyriciproducens SR79 T (SR79), which was identified in the human gut, has been reported to be beneficial in addressing cognitive deficits and pathophysiologies in a mouse model of Alzheimer's disease. However, it remains unknown whether SR79 affects age-dependent cognitive impairment. MAIN METHOD: To explore the effects of SR79 on cognitive function during ageing, we administered SR79 to aged mice. Ageing-associated behavioural alterations were examined using the open field test (OFT), tail suspension test (TST), novel object recognition test (NORT), Y-maze alternation test (Y-maze), and Morris water maze test (MWM). We investigated the mechanisms of action in the gut and brain using molecular and histological analyses. KEY FINDINGS: Administration of SR79 improved age-related cognitive impairment without altering general locomotor activity or depressive behaviour in aged mice. Furthermore, SR79 increased mature dendritic spines in the pyramidal cells of layer III and phosphorylation of CaMKIIα in the cortex of aged mice. Age-related activation of astrocytes in the cortex of layers III-V of the aged brain was reduced following SR79 administration. Additionally, SR79 markedly increased IL-10 production and Foxp3 and Muc2 mRNA expression in the colons of aged mice. SIGNIFICANCE: These findings suggest that treatment with SR79 may be a beneficial microbial-based approach for enhancing cognitive function during ageing.

High-Performance Self-Powered Quantum Dot Infrared Photodetector with Azide Ion Solution Treated Electron Transport Layer.

The demand for self-powered photodetectors (PDs) capable of NIR detection without external power is growing with the advancement of NIR technologies such as LIDAR and object recognition. Lead sulfide quantum dot-based photodetectors (PbS QPDs) excel in NIR detection; however, their self-powered operation is hindered by carrier traps induced by surface defects and unfavorable band alignment in the zinc oxide nanoparticle (ZnO NP) electron-transport layer (ETL). In this study, an effective azide-ion (N3 - ) treatment is introduced on a ZnO NP ETL to reduce the number of traps and improve the band alignment in a PbS QPD. The ZnO NP ETL treated with azide ions exhibited notable improvements in carrier lifetime and mobility as well as an enhanced internal electric field within the thin-film heterojunction of the ZnO NPs and PbS QDs. The azide-ion-treated PbS QPD demonstrated a increase in short-circuit current density upon NIR illumination, marking a responsivity of 0.45 A W-1 , specific detectivity of 4 × 1011 Jones at 950 nm, response time of 8.2 µs, and linear dynamic range of 112 dB.

The Monitoring and Management of an Operating Environment to Enhance the Safety of a Container-Type Energy Storage System.

The implementation of an energy storage system (ESS) as a container-type package is common due to its ease of installation, management, and safety. The control of the operating environment of an ESS mainly considers the temperature rise due to the heat generated through the battery operation. However, the relative humidity of the container often increases by over 75% in many cases because of the operation of the air conditioner which pursues temperature-first control. Humidity is a major factor which can cause safety issues such as fires owing to insulation breakdown caused by condensation. However, the importance of humidity control in ESS is underestimated compared to temperature control. In this study, temperature and humidity monitoring and management issues were addressed for a container-type ESS by building sensor-based monitoring and control systems. Furthermore, a rule-based air conditioner control algorithm was proposed for temperature and humidity management. A case study was conducted to compare the conventional and proposed control algorithms and verify the feasibility of the proposed algorithm. The results showed that the proposed algorithm reduced the average humidity by 11.4% compared to the value achieved with the existing temperature control method while also maintaining the temperature.

Causing trouble and being transmissible: COVID-19 survivors' experiences of stigma and discrimination in South Korea.

Background: The stigma associated with coronavirus disease (COVID-19) is relatively neglected in policies for handling the disease. Stigmatization occurs only within specific social contexts in local societies. Objective: This study aims to examine COVID-19 survivors' experiences of social stigma and discrimination in South Korea in the first 2 years of the pandemic. Methods: Semi-structured interviews were conducted. Results: Of 52 participants, 45 reported that they had to cope with stigma and discrimination in their intimate social relationships, workplaces, and children's schools, ranging from subtle actions to job loss. Sexual minorities who were involved in mass disease transmission in the early part of the pandemic experienced a higher level of stigmatization. The stigmatization dealt with in this study was related to two themes: survivors' sense of causing trouble and possibility of transmission. Conclusion: By intertwining this stigma with the experiences of public health measures through the voices of survivors, this study reveals the local context of East Asia in terms of culture-specific aspects of COVID-19-related stigma.

Agathobaculum butyriciproducens Shows Neuroprotective Effects in a 6-OHDA-Induced Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. Agathobaculum butyriciproducens SR79T (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)-induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3ß signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6-OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.

Humulus japonicus attenuates LPS-and scopolamine-induced cognitive impairment in mice.

BACKGROUND: Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer's disease and Parkinson's disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed. RESULTS: We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model. CONCLUSIONS: These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice.

Prevalent toxin types of Clostridium botulinum in South Korean cattle farms.

Clostridium botulinum produces neurotoxic substrates that can cause fatal flaccid paralysis called botulism. These neurotoxins are classified into types A-G. Several botulism cases were recorded in 2012-2013 in the Gyeonggi province, South Korea. We assessed the distribution of C. botulinum types B, C, and D in several South Korean farms. A total of 184 samples collected in 2012-2013, including feces (n = 72), hay and silage (n = 50), soil (n = 26), water trough (n = 21), and stomach contents (n = 15), were subjected to multiplex polymerase chain reaction (PCR) to screen for types B, C, and D. Twenty-four samples tested PCR-positive as follows: type B (n = 11), type C/D (n = 4), and type D (n = 18). Eight of the 11 type B samples were detected in hay and silage. Sixteen of the 18 type D samples were detected in fecal and stomach content samples. PCR-positivity was observed in fecal (n = 9, 12.5%), hay and silage (n = 10, 20.0%), water trough (n = 2, 9.5%), and stomach content (n = 12, 80.0%) samples. Fourteen (42.4%) C. botulinum-positive samples were isolated from the PCR-positive samples (type B [n = 8], type C/D [n = 1], and type D [n = 5]). Our findings demonstrate that C. botulinum types B, C/D, and D were prevalent in South Korean cattle farms between 2012 and 2013.

Impact of vision and hearing impairments on risk of cardiovascular outcomes and mortality in patients with type 2 diabetes: A nationwide cohort study.

AIMS/INTRODUCTION: The purpose of this study was to investigate the impact of vision and hearing impairments on the risk of adverse cardiovascular outcomes and mortality in patients with type 2 diabetes using a nationwide longitudinal cohort. MATERIALS AND METHODS: We enrolled 771,128 patients with type 2 diabetes who underwent the National Health Screening Program in 2009. We carried out Cox proportional hazards regression analyses to calculate the hazard ratios (HR) of myocardial infarction (MI), stroke, and mortality in those with or without vision and hearing impairments. Subgroup analyses of patients stratified by age, sex and diabetic retinopathy were carried out. RESULTS: Diabetes patients with either vision or hearing impairment showed higher risk of MI, stroke or death compared with those without. Among the combinations of impairments, patients with both vision and hearing impairments had the highest risk for MI (adjusted HR [aHR] 1.362, 95% confidence interval [CI] 1.252-1.481) and mortality (aHR 1.591, 95% CI 1.532-1.651). Those with only vision impairment showed higher risk of MI (aHR 1.324, 95% CI 1.275-1.375 and aHR 1.117, 95% CI 1.066-1.170, respectively), stroke (aHR 1.318, 95% CI 1.276-1.362 and aHR 1.134 95% CI 1.089-1.180, respectively) and mortality (aHR 1.417, 95% CI 1.390-1.446 and aHR 1.163, 95% CI 1.135-1.191, respectively) compared with those with only hearing impairment. CONCLUSIONS: Vision and hearing impairments are independently important risk factors for adverse cardiovascular events and mortality in patients with type 2 diabetes. Vision and hearing impairments synergistically increased the risk of MI and all-cause deaths, but not stroke. In addition, in patients aged <65 years, the HR of vision impairment was higher than those with vision and hearing impairments.

Humulus japonicus rescues autistic­like behaviours in the BTBR T+ Itpr3tf/J mouse model of autism.

Humulus japonicus (HJ) is a traditional herbal medicine that exhibits anti­inflammatory, antimicrobial and anti­tumor effects that is used for the treatment of hypertension, pulmonary disease and leprosy. Recently, it has also been reported that HJ demonstrates neuroprotective properties in animal models of neurodegenerative diseases. The current study hypothesised that the administration of HJ would exhibit therapeutic effects in autism spectrum disorder (ASD), a neurodevelopmental disorder with lifelong consequences. The BTBR T+ Itpr3tf/J mouse model of ASD was used to investigate the anti­autistic like behavioural effects of HJ. Chronic oral administration of the ethanolic extract of HJ significantly increased social interaction, attenuated repetitive grooming behaviour and improved novel­object recognition in BTBR mice. Anti­inflammatory effects of HJ in the brain were analysed using immunohistochemistry and reverse­transcription quantitative PCR analysis. Microglia activation was markedly decreased in the striatum and hippocampus, and pro­inflammatory cytokines, including C­C Motif Chemokine Ligand 2, interleukin (IL)­1ß and IL­6, were significantly reduced in the hippocampus following HJ treatment. Moreover, HJ treatment normalised the phosphorylation levels of: N­methyl­D­aspartate receptor subtype 2B and calcium/calmodulin­dependent protein kinase type II subunit α in the hippocampus of BTBR mice. The results of the present study demonstrated that the administration of HJ may have beneficial potential for ameliorating behavioural deficits and neuroinflammation in ASD.

Sodium phenylbutyrate reduces repetitive self-grooming behavior and rescues social and cognitive deficits in mouse models of autism.

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed the therapeutic effects of NaPB, which is a chemical chaperone as well as histone deacetylase inhibitor on a BTBR T + Itpr3tf/J (BTBR) mice model of ASD. We found that acute and chronic treatment of NaPB remarkably improved, not only core ASD symptoms, including repetitive behaviors and sociability deficit, but also cognitive impairment in the BTBR mice. NaPB substantially induced histone acetylation in the brain of the BTBR mice. Intriguingly, the therapeutic effects of NaPB on autistic-like behaviors, such as repetitive behaviors, impaired sociability, and cognitive deficit also showed in the valproic acid (VPA)-induced mouse model of autism. In addition, pentylenetetrazole (PTZ)-induced seizure was significantly attenuated by NaPB treatment in C57BL/6J and BTBR mice. These findings suggest that NaPB may provide a novel therapeutic approach for the treatment of patients with ASD.

Human gut microbiota Agathobaculum butyriciproducens improves cognitive impairment in LPS-induced and APP/PS1 mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, and is characterized by the accumulation and presence of amyloid plaques (Aß), tangles, dementia, and cognitive impairment. Currently, there is no known cure for AD; however, recently, the association between alteration of the gut microbiota and AD pathology has been explored to find novel therapeutic approaches. Microbiota-targeted intervention has been suggested as an attractive therapeutic approach for AD. Agathobaculum butyriciproducens (SR79) is a strict anaerobic and butyric acid-producing bacteria. We hypothesized that administration of SR79 might have a beneficial effect on cognitive deficits and AD pathologies. To determine the therapeutic effects of SR79 on AD pathologies, APP/PS1 transgenic and lipopolysaccharide -induced cognitive impairment mouse models were used. In the lipopolysaccharide -induced cognitive deficit model, the administration of SR79 improved cognitive function and decreased microglia activation. In addition, the administration of SR79 to APP/PS1 mice significantly improved novel object recognition and percent alteration results in novel object recognition and Y-maze alteration tests. Furthermore, Aß plaque deposition and microglial activation were markedly reduced in the parietal cortex and hippocampus after SR79 treatment in APP/PS1 mice. SR79 treatment significantly decreased gene expression levels of IL-1ß and C1QB and increased the gene expression levels of IGF-1 and thereby the downstream signaling pathway in the cortex of APP/PS1 mice. In conclusion, SR79 administration improved cognitive function and AD pathologies through the regulation of neuroinflammation and IGF-1 signaling in an animal model.

ß­Lapachone ameliorates L­DOPA­induced dyskinesia in a 6­OHDA­induced mouse model of Parkinson's disease.

The dopamine precursor 3,4­dihydroxyphenyl­ l­alanine (L­DOPA) is the most widely used symptomatic treatment for Parkinson's disease (PD); however, its prolonged use is associated with L­DOPA­induced dyskinesia in more than half of patients after 10 years of treatment. The present study investigated whether co­treatment with ß­Lapachone, a natural compound, and L­DOPA has protective effects in a 6­hydroxydopamine (6­OHDA)­induced mouse model of PD. Unilateral 6­OHDA­lesioned mice were treated with vehicle or ß­Lapachone (10 mg/kg/day) and L­DOPA for 11 days. Abnormal involuntary movements (AIMs) were scored on days 5 and 10. ß­Lapachone (10 mg/kg) co­treatment with L­DOPA decreased the AIMs score on both days 5 and 10. ß­Lapachone was demonstrated to have a beneficial effect on the axial and limb AIMs scores on day 10. There was no significant suppression in dopamine D1 receptor­related and ERK1/2 signaling in the DA­denervated striatum by ß­Lapachone­cotreatment with L­DOPA. Notably, ß­Lapachone­cotreatment with L­DOPA increased phosphorylation at the Ser9 site of glycogen synthase kinase 3ß (GSK­3ß), indicating suppression of GSK­3ß activity in both the unlesioned and 6­OHDA­lesioned striata. In addition, astrocyte activation was markedly suppressed by ß­Lapachone­cotreatment with L­DOPA in the striatum and substantia nigra of the unilateral 6­OHDA model. These findings suggest that ß­Lapachone cotreatment with L­DOPA therapy may have therapeutic potential for the suppression or management of the development of L­DOPA­induced dyskinesia in patients with PD.

Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis.

PTPRT has been known to regulate synaptic formation and dendritic arborization of hippocampal neurons. PTPRT-/- null and PTPRT-D401A mutant mice displayed enhanced depression-like behaviors compared with wild-type mice. Transient knockdown of PTPRT in the dentate gyrus enhanced the depression-like behaviors of wild-type mice, whereas rescued expression of PTPRT ameliorated the behaviors of PTPRT-null mice. Chronic stress exposure reduced expression of PTPRT in the hippocampus of mice. In PTPRT-deficient mice the expression of GluR2 (also known as GRIA2) was attenuated as a consequence of dysregulated tyrosine phosphorylation, and the long-term potentiation at perforant-dentate gyrus synapses was augmented. The inhibitory synaptic transmission of the dentate gyrus and hippocampal GABA concentration were reduced in PTPRT-deficient mice. In addition, the hippocampal expression of GABA transporter GAT3 (also known as SLC6A11) was decreased, and its tyrosine phosphorylation was increased in PTPRT-deficient mice. PTPRT-deficient mice displayed reduced numbers and neurite length of newborn granule cells in the dentate gyrus and had attenuated neurogenic ability of embryonic hippocampal neural stem cells. In conclusion, our findings show that the physiological roles of PTPRT in hippocampal neurogenesis, as well as synaptic functions, are involved in the pathogenesis of depressive disorder.

Metformin regulates astrocyte reactivity in Parkinson's disease and normal aging.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary medication for the management of type 2 diabetes. We previously showed that co-treatment with metformin and 3,4-dihydroxyphenyl-l-alanine (l-DOPA) prevented the development of l-DOPA-induced dyskinesia in a 6-hydroxydopamine (6-OHDA)-lesioned animal model of PD. However, effects of metformin on PD- and aging-induced genes in reactive astrocytes remain unknown. In this study, we assessed the effect of metformin on motor function, neuroprotection, and reactive astrocytes in the 6-OHDA-induced PD animal model. In addition, the effects of metformin on the genes expressed by specific types of astrocytes were analyzed in PD model and aged mice. Here, we showed that metformin treatment effectively improves the motor symptoms in the 6-OHDA-induced PD mouse model, whereas metformin had no effect on tyrosine hydroxylase-positive neurons. The activation of AMPK and BDNF signaling pathways was induced by metformin treatment on the 6-OHDA-lesioned side of the striatum. Metformin treatment caused astrocytes to alter reactive genes in a PD animal model. Moreover, aging-induced genes in reactive astrocytes were effectively regulated or suppressed by metformin treatment. Taken together, these results suggest that metformin should be evaluated for the treatment of Parkinson's disease and related neurologic disorders characterized by astrocyte activation.

NQO1 regulates pharmaco-behavioral effects of d-amphetamine in striatal dopaminergic system in mice.

The NAD(P)H:quinone oxidoreductase 1 (NQO1) gene encodes a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones to hydroquinones. A polymorphic form of NQO1 is associated with mood disorders such as schizophrenia. However, the role of NQO1 in dopaminergic system has not yet been elucidated. To determine the role of NQO1 in the dopaminergic system, we investigated pharmaco-behavioral effects of d-amphetamine using NQO1-deficienct mice. According to our comparative study involving NQO1+/+ and NQO1-/- mice, NQO1 deficiency increased d-amphetamine-induced psychomotor activity and psychological dependency compared to wild-type mice. Basal and d-amphetamine-induced dopamine levels were also enhanced by NQO1 deficiency. In NQO1-/- mice, neural activation induced by d-amphetamine was higher in dorsolateral striatum, but not in dorsomedial and ventral striata. Although protein level of CaMKIIα, which is a key player in amphetamine-induced dopamine efflux, was decreased in striata of NQO1-/- mice, phosphorylation of CaMKIIα was markedly enhanced in NQO1-/- mice compared to wild-type mice. Interestingly, experiments with pharmacological antagonist showed that D2 antagonist-induced suppression of locomotion required activation of NQO1. Moreover, the rewarding effect in response to D1 agonist was increased by NQO1 deficiency. These results suggest that striatal NQO1 is of considerable interest to understand the mechanism of dopaminergic regulation of psychiatric disorders.

Elevated M2 Macrophage Markers in Epiretinal Membranes With Ectopic Inner Foveal Layers.

Purpose: To analyze the differences in the vitreous cytokine profiles in epiretinal membrane eyes with and without an ectopic inner foveal layer (EIFL). Methods: Sixty eyes with epiretinal membrane (32 eyes without EIFL and 28 eyes with EIFL) were included. The vitreous samples were collected during surgery for epiretinal membrane. The cytokine levels of the vitreous were measured using a multiplex bead analysis. Results: The mean logMAR visual acuity was worse (0.42 vs. 0.37; P = 0.331) and the central foveal thickness was higher in the EIFL group (496.9 µm vs. 434.2 µm; P = 0.007) than they were in the group without EIFL. The mean EIFL thickness was 164.1 ± 67.7 µm in the EIFL group. On multiplex analysis of the vitreous cytokines, the levels of CD163 (21529 pg/dL vs. 10877 pg/dL; P = 0.002) and macrophage colony-stimulating factor (206 pg/dL vs. 159 pg/dL, P = 0.004) were significantly higher in the EIFL group than they were in the group without EIFL. Conclusions: Eyes with EIFL had increased vitreous levels of M2 macrophage markers. The activation of glial cell proliferation by M2 macrophages may contribute to EIFL formation.

Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice.

Piperlongumine (PL), a biologically active compound from the Piper species, has been shown to exert various pharmacological effects in a number of conditions, including tumours, diabetes, pain, psychiatric disorders and neurodegenerative disease. In this study, we evaluated the therapeutic effects of PL on hippocampal function and cognition decline in aged mice. PL (50 mg/kg/day) was intragastrically administrated to 23­month­old female C57BL/6J mice for 8 weeks. Novel object recognition and nest building behaviour tests were used to assess cognitive and social functions. Additionally, immunohistochemistry and western blot analysis were performed to examine the effects of PL on the hippocampus. We found that the oral administration of PL significantly improved novel object recognition and nest building behaviour in aged mice. Although neither the percentage area occupied by astrocytes and microglia nor the level of 4­hydroxynonenal protein, a specific marker of lipid peroxidation, were altered by PL treatment, the phosphorylation levels of N­methyl­D­aspartate receptor subtype 2B (NR2B), calmodulin­dependent protein kinase II alpha (CaMKIIα) and extracellular signal­regulated kinase 1/2 (ERK1/2) were markedly increased in the hippocampus of aged mice following the administration of PL. We also found that PL treatment resulted in a CA3­specific increase in the phosphorylation level of cyclic AMP response element binding protein, which is recognized as a potent marker of neuronal plasticity, learning and memory. Moreover, the number of doublecortin­positive cells, a specific marker of neurogenesis, was significantly increased following PL treatment in the dentate gyrus of the hippocampus. On the whole, these data demonstrate that PL treatment may be a potential novel approach in the treatment of age­related cognitive impairment and hippocampal changes.

Effects of histone acetyltransferase inhibitors on L-DOPA-induced dyskinesia in a murine model of Parkinson's disease.

Histone acetylation is a key regulatory factor for gene expression in cells. Modulation of histone acetylation by targeting of histone acetyltransferases (HATs) effectively alters many gene expression profiles and synaptic plasticity in the brain. However, the role of HATs on L-DOPA-induced dyskinesia of Parkinson's disease (PD) has not been reported. Our aim was to determine whether HAT inhibitors such as anacardic acid, garcinol, and curcumin from natural plants reduce severity of L-DOPA-induced dyskinesia using a unilaterally 6-hydroxydopamine (6-OHDA)-lesioned PD mouse model. Anacardic acid 2 mg/kg, garcinol 5 mg/kg, or curcumin 100 mg/kg co-treatment with L-DOPA significantly reduced the axial, limb, and orofacial (ALO) score indicating less dyskinesia with administration of HAT inhibitors in 6-OHDA-lesioned mice. Additionally, L-DOPA's efficacy was not altered by the compounds in the early stage of treatment. The expression levels of c-Fos, Fra-2, and Arc were effectively decreased by administration of HAT inhibitors in the ipsilateral striatum. Our findings indicate that HAT inhibitor co-treatment with L-DOPA may have therapeutic potential for management of L-DOPA-induced dyskinesia in patients with PD.