The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events.

BACKGROUND: The global prevalence of VCI has increased steadily in recent years, but diagnostic biomarkers for VCI in patients with non-disabling ischemic cerebrovascular incidents (NICE) remain indefinite. The primary objective of this research was to investigate the relationship between peripheral serological markers, white matter damage, and cognitive function in individuals with NICE. METHODS: We collected clinical data, demographic information, and medical history from 257 patients with NICE. Using the MoCA upon admission, patients were categorized into either normal cognitive function (NCF) or VCI groups. Furthermore, they were classified as having mild white matter hyperintensity (mWMH) or severe WMH based on Fazekas scores. We then compared the levels of serological markers between the cognitive function groups and the WMH groups. RESULTS: Among 257 patients with NICE, 165 were male and 92 were female. Lymphocyte count (OR = 0.448, P < 0.001) and LDL-C/HDL-C (OR = 0.725, P = 0.028) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age and inflammation markers but a lower MoCA score, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.765, P < 0.001) and LDL-C/HDL-C (AUC = 0.740, P < 0.001) had an acceptable diagnostic value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. CONCLUSION: Lymphocyte count, LDL-C/HDL-C were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

Association of neutrophil to lymphocyte ratio and D-dimer with functional outcome in patients with cerebral venous sinus thrombosis.

BACKGROUND: Investigations on the risk factors for the prognosis of cerebral venous sinus thrombosis (CVST) are limited. This study aimed to explore whether specific inflammatory factors and coagulation indictors are associated with functional outcome in patients treated for CVST. METHODS: This retrospective study included 137 patients admitted to our hospital between January 2010 and October 2021. The functional outcome was assessed with the modified Rankin Scale (mRS) score at discharge. Patients were divided into two groups, 102 patients with favorable outcomes (mRS 0-1) and 35 patients with poor outcomes (mRS 2-6). The clinical indexes were compared between two groups. Multivariable logistic regression was performed to identify the independent influencing factors for poor outcomes of CVST patients. The prognostic indicators were analyzed using the receiver operating characteristic (ROC) curve. RESULTS: Compared with the favorable outcome group, the incidence of impaired consciousness and brain lesion, the levels of D-dimer, RDW, neutrophil count, neutrophil to lymphocyte ratio (NLR) and red blood cell distribution width to platelet ratio (%) on admission were significantly higher in the poor outcome group, while the level of lymphocyte count was significantly lower. After multivariable logistic regression analysis, baseline D-dimer level (odds ratio (OR), 1.180; 95% confidence interval (CI), 1.019-1.366, P = 0.027) and NLR (OR, 1.903; 95%CI, 1.232-2.938, P = 0.004) were significantly associated with unfavorable outcome at discharge. The ROC curve analysis showed that the areas under the curve of D-dimer, NLR and their combined detection for predicting worse outcome were 0.719, 0.707 and 0.786, respectively. CONCLUSIONS: Elevated D-dimer level and NLR on admission were associated with an increased risk of poor functional outcome in patients with CVST.

Lower 25-hydroxyvitamin D is associated with severer white matter hyperintensity and cognitive function in patients with non-disabling ischemic cerebrovascular events.

OBJECTIVES: This study aimed to investigate the potential correlations among serum 25-hydroxyvitamin D [25(OH)D] levels, white matter hyperintensity (WMH) and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE). METHODS: This was a prospective investigation of 160 NICE patients with age of 40 years or older. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). White matter lesions were evaluated by WMH using Fazekas scores. Spearman correlation analysis and linear regression models were used to identify the associations between serum 25(OH)D levels and cognitive function. Binary logistic regression analysis models were used to evaluate the predictable value of serum 25(OH)D levels and WMH for cognitive impairment. RESULTS: Patients with inadequate 25(OH)D levels had lower MoCA score (P=0.008), and a higher proportion of severe WMH (P=0.043). Spearman correlation analysis demonstrated that serum 25(OH)D concentrations were positively associated with MoCA score (rs=0.185, P=0.019) while negatively related to the proportion of severe WMH (sWMH) (rs=-0.166, P=0.036).The association between 25(OH)D concentrations and MoCA score remained significant in linear regression (adjusted ß=0.012, 95%CI:0.001-0.203).Adjusted binary logistic regression analysis showed that the odds ratio of cognitive impairment with insufficient 25(OH)D concentration was 5.038 (95%CI:1.154-21.988) compared with the sufficient group and the sWMH (OR=2.728, 95%CI:1.230-6.051) was identified as an independent risk factor for cognitive decline in NICE patients. CONCLUSION: Serum 25(OH)D levels and white matter lesions were independently and significantly associated with cognitive impairment in NICE patients.

A case of ischemic stroke secondary to varicella-zoster virus meningoencephalitis.

Varicella-zoster virus (VZV) lurks in cranial nerves and other brain ganglias after infection. Because middle cerebral artery (MCA) receives the ipsilateral trigeminal ganglia afferent innervations, the reactivated VZV infects the adventitia and intima of cerebral artery wall probably through this way and causes vascular inflammation, finally resulting in artery remodeling, vessel occlusion, and ischemia. In fact, there is a growing clinical recognition that there is an association between VZV reactivation and subsequent stroke. Here, we showed a case of ischemic stroke secondary to varicella-zoster virus meningoencephalitis and reviewed the literature to emphasize the importance of VZV-associated vasculopathy.

Higher inflammation and cerebral white matter injury associated with cognitive deficit in asthmatic patients with depression.

OBJECTIVE: Depression is a common co-morbidity in asthma, worsening asthma control and impairing quality of life. Previous studies have reported a higher risk of cognitive deficit in depression, yet little research has focused on the level of cognition in asthmatic patients with depression. Evidence shows that inflammation may play an important role in both asthma and depression. Cerebral white matter injury, possibly induced by inflammation, has been associated with depression. This study assesses cognitive function in patients with asthma and a depression comorbidity, compared to patients with asthma only or depression only. METHODS: Four groups were studied: Asthma comorbid Depression group (A + D, n = 26), Depression group (D, n = 25), Asthma group (A, n = 33) and Normal controls (N, n = 28). Cognitive function was evaluated using Montreal Cognitive Assessment (MoCA). Inflammatory cytokines were measured, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-mobility group box 1(HMGB1) and Netrin-1. Cerebral white matter injury was assessed by serum myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG), and their correlations with cognitive performance were calculated. RESULTS: A + D group showed the highest incidence of cognitive deficit, with the cognitive domain particularly affected. Compared to N group, serum levels of IL-6, HMGB1, Netrin-1, MBP and MOG were significantly elevated in A + D group. MOG level negatively correlated with the MoCA score. CONCLUSION: Patients with comorbidities presented with more severe cognitive deficits and higher levels of inflammatory cytokines. Cerebral white matter injury may account for the cognitive deficit in patients and MOG could be a potential biomarker for this process.

Anti-neuron antibody syndrome: clinical features, cytokines/chemokines and predictors.

BACKGROUND: Neuroimmunology is a rapidly expanding field, and there have been recent discoveries of new antibodies and neurological syndromes. Most of the current clinical studies have focused on disorders involving one specific antibody. We have summarized a class of antibodies that target common neuronal epitopes, and we have proposed the term "anti-neuron antibody syndrome" (ANAS). In this study, we aimed to clarify the clinical range and analyse the clinical features, cytokines/chemokines and predictors in ANAS. METHODS: This was a retrospective cohort study investigating patients with neurological manifestations that were positive for anti-neuron antibodies. RESULTS: A total of 110 patients were identified, of which 43 patients were classified as having autoimmune encephalitis (AE) and the other 67 were classified as having paraneoplastic neurological syndrome (PNS). With regards to anti-neuron antibodies, 42 patients tested positive for anti-N-methyl-D-aspartate receptor (NMDAR) antibody, 19 for anti-Hu, 14 for anti-Yo and 12 for anti-PNMA2 (Ma2). There were significant differences between the ANAS and control groups in serum B cell-activating factor (BAFF) levels and in cerebrospinal fluid (CSF) C-X-C motif chemokine10 (CXCL10), CXCL13, interleukin10 (IL10), BAFF and transforming growth factor ß1 (TGFß1) levels. Predictors of poor outcomes included having tumours (P = 0.0193) and having a chronic onset (P = 0.0306), and predictors of relapses included having lower levels of CSF BAFF (P = 0.0491) and having a larger ratio of serum TGFß1/serum CXCL13 (P = 0.0182). CONCLUSIONS: Most patients with ANAS had a relatively good prognosis. Having tumours and a chronic onset were both associated with poor outcomes. CSF BAFF and the ratio of serum TGFß1/serum CXCL13 were associated with relapses.

Low field magnetic stimulation promotes myelin repair and cognitive recovery in chronic cuprizone mouse model.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease featured with neuroinflammation, demyelination, and the loss of oligodendrocytes. Cognitive impairment and depression are common neuropsychiatric symptoms in MS that are poorly managed with the present interventions. OBJECTIVE: This study aimed to investigate the effects of low field magnetic stimulation (LFMS), a novel non-invasive neuromodulation technology, on cognitive impairment and depressive symptoms associated with MS using a mouse model of demyelination. METHODS: C57BL female mice were fed with a 0.2% cuprizone diet for 12 weeks to induce a chronic demyelinating model followed by 4 weeks of cuprizone withdrawal with either sham or LFMS treatment. RESULTS: Improved cognition and depression-like behaviour and restored weight gain were observed in mice with LFMS treatment. Immunohistochemical and immunoblotting data showed enhanced myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein expressions (MOG) in the prefrontal cortex of mice with LFMS treatment, supporting that myelin repair was promoted. LFMS also increased the protein expression of mature oligodendrocyte biomarker glutathione-S-transferase (GST-π). In addition, expression of TGF-ß and associated receptors were elevated with LFMS treatment, implicating this pathway in the response. CONCLUSION: Results from the present study revealed LFMS to have neuroprotective effects, suggesting that LFMS has potential therapeutic value for treating cognitive impairment and depression related to demyelination disorders.

Association between alpha-synuclein (SNCA) rs11931074 variability and susceptibility to Parkinson's disease: an updated meta-analysis of 41,811 patients.

BACKGROUND AND OBJECTIVES: Parkinson's disease (PD) is one of the most common forms of neurodegenerative disorders, and its etiology remains unclear. Single nucleotide polymorphisms (SNPs) of alpha-synuclein (SNCA) have been found to be significantly associated with PD risk. In particular, the variant rs11931074 was found in one meta-analysis to appear to play a role in the occurrence of PD. This finding has been questioned in subsequent studies, however. The aim of this study was to determine the relationship between PD risk and rs11931074 polymorphism. METHODS: We performed a systematic online search, including PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI (China National Knowledge Infrastructure), aiming to identify case-control studies looking at the role of rs11931074 in PD. We performed calculations of pooled odds ratio (OR) and 95% confidence interval (95% CI) to assess the associations, and subgroup meta-analyses to verify differences between various ethnicities of different study populations. RESULTS: A total of 13 studies involving 13,403 cases and 28,408 controls met the inclusion criteria after assessment by two reviewers. Overall, there exists significant associations between SNCA rs11931074 polymorphism and the risk of PD under five genetic models (allele contrast model: T vs. G, OR = 1.28, 95% CI = 1.12-1.45, P = 0.0001; homozygote model: TG vs. GG, OR = 1.55, 95% CI = 1.17-2.05, P = 0.002; heterozygote model (TT vs. GG, OR = 1.23, 95% CI = 1.05-1.42, P = 0.009; dominant model: TG+TT vs. GG: OR = 1.25, 95% CI = 1.05-1.50, P = 0.01 and recessive model: TT vs. TG+GG: OR = 1.40, 95% CI = 1.18-1.68, P = 0.0002). When ethnicities were stratified, significant associations were found in the allelic, homozygote, and recessive models for Asians, and in the allelic model for Caucasians. CONCLUSION: SNCA rs11931074 polymorphism is found to be associated with PD risk and this risk appears to be influenced by genetic status and ethnicity.

Disulfiram and Diphenhydramine Hydrochloride Upregulate miR-30a to Suppress IL-17-Associated Autoimmune Inflammation.

UNLABELLED: T-helper 17 (Th17) cells play an important role in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease that affects the CNS. In the present study, MicroRNA sequencing (miRNA-seq) was performed in mouse Th0 and Th17 cells to determine the critical miRNAs that are related to Th17 differentiation. We found that miR-30a was significantly downregulated during mouse Th17 differentiation. In addition, the level of miR-30a in CD4(+) T cells from peripheral blood of MS patients and experimental autoimmune encephalomyelitis (EAE) animal models was also decreased and inversely correlated with the expression of interleukin 17a, the canonical cytokine of Th17 cells. Moreover, overexpression of miR-30a inhibited Th17 differentiation and prevented the full development of EAE, whereas interference of miR-30a promoted Th17 differentiation. Mechanism studies showed that miR-30a reduced IRF4 expression by specifically binding with the 3'-untranslated region. Through screening of 640 different Food and Drug Administration (FDA)-approved drugs, we found that disulfiram and diphenhydramine hydrochloride were effective candidates for inhibiting Th17 differentiation and ameliorating EAE development through upregulating miR-30a. To our knowledge, the present work is not only the first miRNA-seq study focusing on Th17 differentiation, but also the first chemical screening for FDA-approved drugs that inhibit Th17 differentiation through regulating miRNA expression. SIGNIFICANCE STATEMENT: The present work is the first miRNA sequencing (miRNA-seq) study focusing on T-helper 17 (Th17) differentiation. By miRNA deep sequencing, we found that miR-30a was downregulated during Th17 differentiation. miR-30a was also decreased in CD4(+) T cells from multiple sclerosis patients and experimental autoimmune encephalomyelitis (EAE) mice. miR-30a reduced IRF4 expression by specific binding with the 3'-untranslated region and thus suppressed Th17 differentiation and prevented the full development of EAE. Interestingly, by performing a chemical screen with Food and Drug Administration-approved small-molecule drugs, we found that disulfiram and diphenhydramine upregulated miR-30a and suppressed Th17-associated autoimmune demyelination.

MicroRNA-448 promotes multiple sclerosis development through induction of Th17 response through targeting protein tyrosine phosphatase non-receptor type 2 (PTPN2).

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system, and its pathogenesis remains largely unclear. Much attention has been paid to the role of microRNAs (miRs) in regulation of autoimmune disease. Here, we found, for the first time, that miR-448 expression was significantly increased in periphery blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) of patients with MS, and its expression positively correlated with the disease severity. We further demonstrated that CD4+ T cells, especially the Th17 lineage, were the major source of miR-448 expression. Using gain- and loss-of-function approaches, we further verified that miR-448 could enhance Th17 differentiation, characterized by up-regulated expression levels of IL-17A and RORγt. Interleukin (IL)-1ß as a potent driver of pathogenic Th17 cells was able to strongly induce miR-448 expression in CD4+ T cells through activating NF-κB pathway. Additionally, we identified that miR-448 directly targeted protein tyrosine phosphatase non-receptor type 2 (PTPN2), which has been known as an anti-inflammatory player with capacity to suppress Th17 differentiation. We also observed markedly decreased expression of PTPN2 in PBMC and CSF of MS patients. Our results suggest that miR-448 might promote Th17 differentiation in MS and thus aggravate the disease through inhibiting PTPN2.

A retrospective study of 23 cases with subacute combined degeneration.

PURPOSE: To study retrospectively the diverse presentations, ancillary tests and neuroimaging in patients with subacute combined degeneration (SCD). METHODS: Twenty-three Chinese patients with SCD were included in this study. The clinical presentations and laboratory data including comprehensive metabolic panel, serum folic acid, vitamin B12 levels, gastroscopy and images of spinal cord on magnetic resonance imaging (MRI) were evaluated. Rating scales for localizations of lesions and functional disabilities were used to define the severity of neurological impairment. RESULTS: No difference was found between men and women in the age of disease onset. For most of the patients, sensory symptoms, oftentimes as initial symptoms, occurred earlier than motor symptoms. The signs of the disease were more obvious than the symptoms. Six patients had sensory deficit levels mimicking transverse myelopathy. Anemia was not always detected in our patients with SCD. Normal or even elevated serum levels of vitamin B12 were found in seven patients. Spinal cord lesions on MRI were observed in six patients and the clinical and neuroimaging findings were not necessarily consistent. CONCLUSIONS: The sensory symptoms occur earlier than the motor symptoms in SCD patients. SCD patients may have sensory deficit level. Normal or even elevated serum levels of vitamin B12 may occur in patients with SCD.

Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR2 /SRC pathway in vascular cognitive impairment mice.

AIM: To explore the neuroprotective potential of hyperforin and elucidate its underlying molecular mechanisms involved in its therapeutic effects against vascular cognitive impairment (VCI). METHODS: The active compounds and possible targets of Hypericum perforatum L. that may be effective against VCI were found by network pharmacology in this research. We utilized bilateral common carotid artery occlusion (BCCAO) surgery to induce a VCI mouse model. Morris water maze (MWM) and Y-maze tests were used to assess VCI mice's cognitive abilities following treatment with hyperforin. To evaluate white matter lesions (WMLs), we utilized Luxol fast blue (LFB) stain and immunofluorescence (IF). Neuroinflammation was assessed using IF, western blot (WB), and enzyme-linked immunosorbent assay (ELISA). The effects of hyperforin on microglia were investigated by subjecting the BV2 microglial cell line to oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The expressions of VEGFR2 , p-SRC, SRC, VEGFA, and inflammatory markers including IL-10, IL-1ß, TNF-α, and IL-6 were subsequently assessed. RESULTS: The VEGFR2 /SRC signaling pathway is essential for mediating the protective properties of hyperforin against VCI according to network pharmacology analysis. In vivo findings demonstrated that hyperforin effectively improved BCCAO-induced cognitive impairment. Furthermore, staining results showed that hyperforin attenuated WMLs and reduced microglial activation in VCI mice. The hyperforin treatment group's ELISA results revealed a substantial decrease in IL-1ß, IL-6, and TNF-α levels. According to the results of in vitro experiments, hyperforin decreased the release of pro-inflammatory mediators (TNF-α, IL-6, and IL-1ß) and blocked microglial M1-polarization by modulating the VEGFR2 /SRC signaling pathway. CONCLUSION: Hyperforin effectively modulated microglial M1 polarization and neuroinflammation by inhibiting the VEGFR2 /SRC signaling pathways, thereby ameliorating WMLs and cognitive impairment in VCI mice.

EEG assessment of brain dysfunction for patients with chronic primary pain and depression under auditory oddball task.

In 2019, the International Classification of Diseases 11th Revision International Classification of Diseases (ICD-11) put forward a new concept of "chronic primary pain" (CPP), a kind of chronic pain characterized by severe functional disability and emotional distress, which is a medical problem that deserves great attention. Although CPP is closely related to depressive disorder, its potential neural characteristics are still unclear. This paper collected EEG data from 67 subjects (23 healthy subjects, 22 patients with depression, and 22 patients with CPP) under the auditory oddball paradigm, systematically analyzed the brain network connection matrix and graph theory characteristic indicators, and classified the EEG and PLI matrices of three groups of people by frequency band based on deep learning. The results showed significant differences in brain network connectivity between CPP patients and depressive patients. Specifically, the connectivity within the frontoparietal network of the Theta band in CPP patients is significantly enhanced. The CNN classification model of EEG is better than that of PLI, with the highest accuracy of 85.01% in Gamma band in former and 79.64% in Theta band in later. We propose hyperexcitability in attentional control in CPP patients and provide a novel method for objective assessment of chronic primary pain.

Prediction of subjective cognitive decline after corpus callosum infarction by an interpretable machine learning-derived early warning strategy.

Background and purpose: Corpus callosum (CC) infarction is an extremely rare subtype of cerebral ischemic stroke, however, the symptoms of cognitive impairment often fail to attract early attention of patients, which seriously affects the long-term prognosis, such as high mortality, personality changes, mood disorders, psychotic reactions, financial burden and so on. This study seeks to develop and validate models for early predicting the risk of subjective cognitive decline (SCD) after CC infarction by machine learning (ML) algorithms. Methods: This is a prospective study that enrolled 213 (only 3.7%) CC infarction patients from a nine-year cohort comprising 8,555 patients with acute ischemic stroke. Telephone follow-up surveys were carried out for the patients with definite diagnosis of CC infarction one-year after disease onset, and SCD was identified by Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. Based on the significant features selected by the least absolute shrinkage and selection operator (LASSO), seven ML models including Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost), Gaussian Naïve Bayes (GNB), Complement Naïve Bayes (CNB), and Support vector machine (SVM) were established and their predictive performances were compared by different metrics. Importantly, the SHapley Additive exPlanations (SHAP) was also utilized to examine internal behavior of the highest-performance ML classifier. Results: The Logistic Regression (LR)-model performed better than other six ML-models in SCD predictability after the CC infarction, with the area under the receiver characteristic operator curve (AUC) of 77.1% in the validation set. Using LASSO and SHAP analysis, we found that infarction subregions of CC infarction, female, 3-month modified Rankin Scale (mRS) score, age, homocysteine, location of angiostenosis, neutrophil to lymphocyte ratio, pure CC infarction, and number of angiostenosis were the top-nine significant predictors in the order of importance for the output of LR-model. Meanwhile, we identified that infarction subregion of CC, female, 3-month mRS score and pure CC infarction were the factors which independently associated with the cognitive outcome. Conclusion: Our study firstly demonstrated that the LR-model with 9 common variables has the best-performance to predict the risk of post-stroke SCD due to CC infarcton. Particularly, the combination of LR-model and SHAP-explainer could aid in achieving personalized risk prediction and be served as a decision-making tool for early intervention since its poor long-term outcome.

Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration.

Background: Major depression disorder (MDD) is a devastating neuropsychiatric disease, and one of the leading causes of suicide. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in numerous diseases. The study aimed to construct and validate a gene signature for diagnosing MDD based on ferroptosis-related genes (FRGs) and further explore the biological functions of these genes in MDD. Methods: The datasets were downloaded from the Gene Expression Omnibus (GEO) database and FRGs were obtained from the FerrDb database and other literatures. Least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were performed to develop a gene signature. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic power of the signature. Gene ontology (GO) enrichment analysis was used to explore the biological roles of these diagnostic genes, and single sample gene set enrichment analysis (ssGSEA) algorithm was used to evaluate immune infiltration in MDD. Animal model of depression was constructed to validate the expression of the key genes. Results: Eleven differentially expressed FRGs were identified in MDD patients compared with healthy controls. A signature of three FRGs (ALOX15B, RPLP0, and HP) was constructed for diagnosis of MDD. Afterwards, ROC analysis confirmed the signature's discriminative capacity (AUC = 0.783, 95% CI = 0.719-0.848). GO enrichment analysis revealed that the differentially expressed genes (DEGs) related to these three FRGs were mainly involved in immune response. Furthermore, spearman correlation analysis demonstrated that these three FRGs were associated with infiltrating immune cells. ALOX15B and HP were significantly upregulated and RPLP0 was significantly downregulated in peripheral blood of the lipopolysaccharide (LPS)-induced depressive model. Conclusion: Our results suggest that the novel FRG signature had a good diagnostic performance for MDD, and these three FRGs correlated with immune infiltration in MDD.

In Situ Halide Exchange of Cesium Lead Halide Perovskites for Blue Light-Emitting Diodes.

3D perovskites are promising to achieve efficient and bright deep-blue light-emitting diodes (LEDs), which are required for lighting and display applications. However, the efficiency of deep-blue 3D perovskite-based LEDs is limited by high density of defects in perovskites, and their deep-blue emission is not easy to achieve due to the halide phase separation and low solubility of chloride in precursor solutions. Here, an in situ halide exchange method is developed to achieve deep-blue 3D perovskites by spin-coating an organic halide salts solution to treat blue 3D perovskites. It is revealed that the halide-exchange process is mainly determined by halide ion diffusion targeting a concentration equalization, which leads to homogeneous 3D mixed-halide perovskites. By further introducing multifunctional organic ammonium halide salts into the exchange solution to passivate defects, high-quality deep-blue perovskites with reduced trap density can be obtained. This approach leads to efficient deep-blue perovskite LEDs with a peak external quantum efficiency (EQE) of 4.6% and a luminance of 1680 cd m-2 , which show color coordinates of (0.131, 0.055), very close to the Rec. 2020 blue standard. Moreover, the halide exchange method is bidirectional, and blue perovskite LEDs can be achieved with color coordinates of (0.095, 0.160), exhibiting a high EQE of 11.3%.

Quetiapine prevents oligodendrocyte and myelin loss and promotes maturation of oligodendrocyte progenitors in the hippocampus of global cerebral ischemia mice.

White matter impairment is a feature of vascular depression. The anti-psychotic quetiapine has been shown to enhance the therapeutic effects of anti-depressants on vascular depression, but the mechanism remains unknown. In this study, we found that 2 weeks of treatment with quetiapine prior to bilateral carotid artery occlusion and reperfusion, in an animal model of vascular depression, resulted in reduced myelin breakdown and oligodendrocyte loss compared to placebo-treated mice on post-operative day (POD) 7. For late stage of recovery (POD40), quetiapine treatment resulted in enhanced oligodendrocyte maturation relative to placebo. The results suggest that quetiapine is a potential intervention for oligodendrocyte damage and this may contribute to its anti-depressant effects through white matter protection in vascular depression.

Impact of Stress Hyperglycemia on Early Neurological Deterioration in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background and Purpose: It has been widely reported that stress hyperglycemia contributes to poor prognosis in patients experiencing acute ischemic stroke (AIS). However, its predictive value for early neurological deterioration (END) after intravenous administration of recombinant tissue-type plasminogen activator (IV-rtPA) in AIS patients is still unclear. The aim of this study was to evaluate the impact of stress hyperglycemia on the risk of END after IV-rtPA. Methods: A total of 798 consecutive patients treated with IV-rtPA were included in this study. The stress hyperglycemia ratio (SHR) was calculated as fasting plasma glucose level at admission (mg/dl)/glycosylated hemoglobin (HbAlc) (%). END was defined as a National Institutes of Health Stroke Scale Score (NIHSS) ≥ 4 points 24 h after IV-rtPA, and poor functional outcome at discharge was defined as a modified Rankin Scale (mRS) score of 3-6 at discharge. Patients with a prior history of diabetes or HbAlc ≥ 6.5% were considered to have diabetes mellitus. Patients were grouped according to SHR values. Multivariate logistical regression was used to evaluate the risk of END for patients within specific SHR categories. Results: In total, 139 (17.4%) patients had END. After adjusting for confounders, the highest tertile group had higher risks of END and poor functional outcome at discharge than those of patients in the lowest tertile group (OR, 1.95; 95% CI, 1.21-3.15; p = 0.006) (OR, 1.85; 95% CI, 1.163-2.941; p = 0.009), and the predictive value of high SHR for END was also significant in patients with diabetes mellitus (OR, 3.05; 95% CI, 1.29-7.21; p = 0.011). However, a significant association of high SHR and poor functional outcome was only found in patients without diabetes (OR, 1.85; 95% CI, 1.002-3.399; p = 0.045). Conclusion: A higher SHR predicted that patients with severe stress hyperglycemia had higher risks of END and poor functional outcome at discharge after IV-rtPA.