Navigating the Complex Terrain of Dysregulated Microglial Function in Depressive Disorders: Insights, Challenges and Future Directions.

Microglia are crucial immune cells found in the central nervous system. Multiple investigations have substantiated the correlation between the development of depression and neuroinflammation resulting from impaired microglial activity. Through extensive research on the phenotype, function, imaging technology, multi-omics analysis, and in vitro culture of microglia in depressive disorder, the understanding of the relationship between microglia and depression has become more intricate. Various therapeutic approaches have been suggested, but a thorough analysis of the obstacles to clinical application has not been conducted. This paper explores the innovative advancement of microglia detection technology, recent research findings on microglia identification and epigenetic modification, the variability of microglia in different conditions, the relationship between microglia dysfunction and the onset of depression, the progress and challenges of microglia-targeted therapy for depression, and the current obstacles and future prospects in studying dysregulated microglial function in depressive disorders.

NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.

Docetaxel is the preferred chemotherapeutic agent in patients with castrate-resistant prostate cancer (CRPC). However, patients eventually develop docetaxel resistance and in the absence of effective treatment options. Consequently, it is essential to investigate the mechanisms generating docetaxel resistance and develop novel alternative therapeutic targets. RNA sequencing was undertaken on docetaxel-sensitive and docetaxel-resistant prostate cancer (PCa) cells. Subsequently, chemoresistance, cancer stemness, and lipid metabolism were investigated. To obtain insight into the precise activities and action mechanisms of NOTCH3 in docetaxel-resistant PCa, immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, cell metabolism, and animal experiments were performed. Through RNA sequencing analysis, we found that NOTCH3 expression was markedly higher in docetaxel-resistant cells relative to parental cells, and that this trend was continued in docetaxel-resistant PCa tissues. Experiments in vitro and in vivo revealed that NOTCH3 enhanced stemness, lipid metabolism, and docetaxel resistance in PCa. Mechanistically, NOTCH3 is bound to TUBB3 and activates the MAPK signaling pathway. Moreover, NOTCH3 was directly regulated by MEF2A in docetaxel-resistant cells. Notably, targeting NOTCH3 and the MEF2A/TUBB3 signaling axis was related to docetaxel chemoresistance in PCa. Overall, these results demonstrated that NOTCH3 fostered stemness, lipid metabolism, and docetaxel resistance in PCa via the TUBB3 and MAPK signaling pathways. Therefore, NOTCH3 may be employed as a prognostic biomarker in PCa patients. NOTCH3 could be a therapeutic target for PCa patients, particularly those who have developed docetaxel resistance.

ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer.

BACKGROUND: Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq. METHODS: A total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed. RESULTS: The results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence. CONCLUSIONS: The significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role.

Mechanism of Depression through Brain Function Imaging of Depression Patients and Normal People.

In recent years, functional magnetic resonance technology has discovered that abnormal connections in different brain regions of the brain may serve as the pathophysiological mechanism of mental illness. Exploring the mechanism of information flow and integration between different brain regions is of great significance for understanding the pathophysiological mechanism of mental illness. This article aims to analyze the mechanism of depression by comparing human brain images of normal people and patients with depression and conduct research. Fluoxetine, a selective 5-HT reuptake inhibitor (SSRI) widely used in clinical practice, can selectively inhibit 5-HT transporter and block the reuptake of 5-HT by the presynaptic membrane. The effect of 5-HT is prolonged and increased, thereby producing antidepressant effects. It has low affinity for adrenergic, histaminergic, and cholinergic receptors and has a weaker effect, resulting in fewer adverse reactions. This paper uses the comparative experiment method and the Welch method and uses the average shortest path length L to describe the average value of the shortest path length between two nodes in the network. Attention refers to the ability of a person's mental activity to point and to concentrate on something. Sustained attention means that attention is kept on a certain cognitive object or activity for a certain period of time, which is also called the stability of attention. The research on attention of depression patients generally focuses on continuous attention, and the results obtained show inconsistencies. Most studies have shown that the sustained attention of the depression group is significantly worse than that of the healthy control group. An overview of magnetic resonance imaging technology and an analysis of depression based on resting state were carried out. The key brain areas of the sample core network were scanned, and the ALFF results were analyzed. The data showed that the severity of depression in the depression group was negatively correlated with the ReHo value in the posterior left cerebellum (P=0.010). The sense of despair was negatively correlated with the ReHo value in the posterior right cerebellum (P=0.013). The diurnal variation was negatively correlated with the ReHo value of the left ring (P=0.014). It was positively correlated with the ReHo value of the left ventricle (P=0.048). This experiment has better completed the research on the mechanism of depression by analyzing the functional images of patients with depression and normal human brain.

Identification of Nephrogenic Therapeutic Biomarkers of Wilms Tumor Using Machine Learning.

Wilms tumor is the most common renal malignancy in children, with a survival rate of more than 90%; however, treatment outcomes for certain patient subgroups, such as those with bilateral and recurrent diseases, remain significantly below this survival rate. Therefore, it remains essential to identify new biomarkers and develop effective therapeutic strategies. Based on the Therapeutically Applicable Research to Generate Effective Treatments and Gene Expression Omnibus RNA microarray datasets, we have identified eight differentially expressed genes in Wilms tumors as renal-specific in 33 randomly selected adult tumors. The risk model, constructed using survival forest and multivariate Cox regression, can effectively predict the prognosis; the risk score is an independent prognostic factor in Wilms tumor. Gene set enrichment analysis showed that most of the signature genes were involved in regulating human development-related pathways. At the same time, patients in the high-risk group exhibited more sensitive immunological and chemotherapeutic properties than those in the low-risk group. These results provide new insights into personalized and precise Wilms tumor treatment strategies.

Development of an Individualized Immune Prognostic Signature for Clear Cell Renal Cell Carcinoma through the Identification of Differential Immune Genes.

Increasing evidence has shown that tumor microenvironments are an important feature in clear cell renal cell carcinoma (ccRCC) carcinogenesis and therapeutic efficacy. In this study, two subtypes of ccRCC, high- and low-immune groups, were identified based on the immune gene datasets, of which the differential immune genes were identified accordingly. Furthermore, we constructed a risk prognosis model using five immune genes, specifically, AQP9, KIAA1429, HAMP, CCL13, and CCL21. This model was highly predictive of ccRCC clinical characteristics and showed potential for use in immunotherapy. Furthermore, the five identified genes were highly correlated with the abundance of B cells, CD4 T cells, CD8 T cells, macrophages, neutrophils, and dendritic cells in the tumor microenvironments. Among them, AQP9, KIAA1429, and HAMP exhibited significant prognostic potential. These findings indicate that monitoring and operating tumor microenvironments are of great significance for ccRCC prognosis and precise immunotherapy.

Metabolic classification of bladder cancer based on multi-omics integrated analysis to predict patient prognosis and treatment response.

BACKGROUND: Currently, no molecular classification is established for bladder cancer based on metabolic characteristics. Therefore, we conducted a comprehensive analysis of bladder cancer metabolism-related genes using multiple publicly available datasets and aimed to identify subtypes according to distinctive metabolic characteristics. METHODS: RNA-sequencing data of The Cancer Genome Atlas were subjected to non-negative matrix fractionation to classify bladder cancer according to metabolism-related gene expression; Gene Expression Omnibus and ArrayExpress datasets were used as validation cohorts. The sensitivity of metabolic types to predicted immunotherapy and chemotherapy was assessed. Kaplan-Meier curves were plotted to assess patient survival. Differentially expressed genes between subtypes were identified using edgeR. The differences among identified subtypes were compared using the Kruskal-Wallis non-parametric test. To better clarify the subtypes of bladder cancer, their relationship with clinical characteristics was examined using the Fisher's test. We also constructed a risk prediction model using the random survival forest method to analyze right-censored survival data based on key metabolic genes. To identify genes of prognostic significance, univariate Cox regression, lasso analysis, and multivariate regression were performed sequentially. RESULTS: Three bladder cancer subtypes were identified according to the expression of metabolism-related genes. The M1 subtype was characterized by high metabolic activity, low immunogenicity, and better prognosis. M2 exhibited moderate metabolic activity, high immunogenicity, and the worst prognosis. M3 was associated with low metabolic activity, low immunogenicity, and poor prognosis. M1 showed the best predicted response to immunotherapy, whereas patients with M1 were predicted to be the least sensitive to cisplatin. By contrast, M2 showed the worst predicted response to immunotherapy but was predicted to be more sensitive to cisplatin, doxorubicin, and other first-line anticancer drugs. M3 was the most sensitive to gemcitabine. The risk model based on metabolic genes effectively predicted the prognosis of bladder cancer patients. CONCLUSIONS: Metabolic classification of bladder cancer has potential clinical value and therapeutic feasibility by inhibiting the associated pathways. This classification can provide valuable insights for developing precise bladder cancer treatment.

Reconstruction and Analysis of the Immune-Related LINC00987/A2M Axis in Lung Adenocarcinoma.

Enhancer RNAs (eRNAs) participate in tumor growth and immune regulation through complex signaling pathways. However, the immune-related function of the eRNA-mRNA axis in lung adenocarcinoma (LUAD) is unclear. Data on the expression of eRNAs and mRNAs were downloaded from The Cancer Genome Atlas, GEO, and UCSC Xena, including LUAD, and pan-cancer clinical data and mutational information. Immune gene files were obtained from ImmLnc and ImmPort databases. Survival indices, including relapse-free and overall survival, were analyzed using the Kaplan-Meier and log-rank methods. The level of immune cell infiltration, degree of tumor hypoxia, and tumor cell stemness characteristics were quantified using the single-sample gene set enrichment analysis algorithm. The immune infiltration score and infiltration degree were evaluated using the ESTIMATE and CIBERSORT algorithms. The tumor mutation burden and microsatellite instability were examined using the Spearman test. The LUAD-associated immune-related LINC00987/A2M axis was down-regulated in most cancer types, indicating poor survival and cancer progression. Immune cell infiltration was closely related to abnormal expression of the LINC00987/A2M axis, linking its expression to a possible evaluation of sensitivity to checkpoint inhibitors and response to chemotherapy. Abnormal expression of the LINC00987/A2M axis was characterized by heterogeneity in the degree of tumor hypoxia and stemness characteristics. The abnormal distribution of immune cells in LUAD was also verified through pan-cancer analysis. Comprehensive bioinformatic analysis showed that the LINC00987/A2M axis is a functional and effective tumor suppressor and biomarker for assessing the immune microenvironment and prognostic and therapeutic evaluations of LUAD.

Identification of Four Immune Subtypes in Bladder Cancer Based on Immune Gene Sets.

Molecular classification of bladder cancer is becoming increasingly important for its clinical management. And, the current classifications are primarily based on gene expression profiles. We identified four immunotypes of bladder cancer (referred to as C1-C4) based on gene expression profiles performed by immune-related gene sets in three independent data sets, and proved that this classification is effective and reproducible. We found that C2 is an immune-infiltrating type and C4 is an immune "desert" type. These types are characterized by the up- and downregulation of genes encoding numerous immune checkpoint proteins and HLA and regulating human immune cell subgroups. The survival rate was better for the C2 subtype than for other subtypes. We believe that this can be explained by the antitumor effects of CD4 memory T cells and CD8 T cells as well as their ability to circumvent M0 macrophage antitumor immunity. In addition, C2 was most sensitive to not only anti-PD-1 immunosuppressive therapy, but also conventional chemotherapeutics such as gemcitabine and bleomycin. The C4 subtype was most sensitive to the chemotherapy drugs cisplatin and doxorubicin. This theoretical framework may guide the personalized treatment of bladder cancer in the future. It is worth noting that the C2 immune infiltration type positively correlates with a variety of stromal components, such as enrichment of endothelial cells and fibroblasts, epithelial-mesenchymal transition, and angiogenesis, together with enrichment of seven kinds of stem cells. We further identified tumor-related JAK-STAT and other signaling pathways in the C2 subtype, along with important mutations in the proteins involved in these pathways, revealing the complex mechanism underlying tumor immune escape. Our results, and particularly the identification of hub genes specific to the C2 and C4 subtypes, provide a reference for the development of immunotherapeutic agents against bladder cancer.

Development and validation of a novel stem cell subtype for bladder cancer based on stem genomic profiling.

BACKGROUND: Bladder cancer (BLCA) is the fifth most common type of cancer worldwide, with high recurrence and progression rates. Although considerable progress has been made in the treatment of BLCA through accurate typing of molecular characteristics, little is known regarding the various genetic and epigenetic changes that have evolved in stem and progenitor cells. To address this issue, we have developed a novel stem cell typing method. METHODS: Based on six published genomic datasets, we used 26 stem cell gene sets to classify each dataset. Unsupervised and supervised machine learning methods were used to perform the classification. RESULTS: We classified BLCA into three subtypes-high stem cell enrichment (SCE_H), medium stem cell enrichment (SCE_M), and low stem cell enrichment (SCE_L)-based on multiple cross-platform datasets. The stability and reliability of the classification were verified. Compared with the other subtypes, SCE_H had the highest degree of cancer stem cell concentration, highest level of immune cell infiltration, and highest sensitivity not only to predicted anti-PD-1 immunosuppressive therapy but also to conventional chemotherapeutic agents such as cisplatin, sunitinib, and vinblastine; however, this group had the worst prognosis. Comparison of gene set enrichment analysis results for pathway enrichment of various subtypes reveals that the SCE_H subtype activates the important pathways regulating cancer occurrence, development, and even poor prognosis, including epithelial-mesenchymal transition, hypoxia, angiogenesis, KRAS signal upregulation, interleukin 6-mediated JAK-STAT signaling pathway, and inflammatory response. Two identified pairs of transcription factors, GRHL2 and GATA6 and IRF5 and GATA3, possibly have opposite regulatory effects on SCE_H and SCE_L, respectively. CONCLUSIONS: The identification of BLCA subtypes based on cancer stem cell gene sets revealed the complex mechanism of carcinogenesis of BLCA and provides a new direction for the diagnosis and treatment of BLCA.

Identification of a prognostic signature of nine metabolism-related genes for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer. Since changes in liver metabolism contribute to liver disease development, it is necessary to build a metabolism-related prognostic model for HCC. METHODS: We constructed a metabolism-related-gene (MRG) signature comprising nine genes, which segregated HCC patients into high- and low-risk groups. RESULTS: The survival rate (overall survival: OS; relapse-free survival; and progression-free survival) of patients in the low-risk group of The Cancer Genome Atlas (TCGA) cohort was significantly higher than that of patients in the high-risk group. The OS prognostic signature was validated in the International Cancer Genome Consortium independent cohort. The corresponding receiver operating characteristic curves of the model indicated that the signature had good diagnostic efficiency, in terms of improving OS over 1, 3, and 5 years. Hierarchical analysis demonstrated that the MRG signature was significantly associated with better prognosis in male patients, patients aged ≤ 65 years, and patients carrying the wild-type TP53 or CTNNB1 genes. A nomogram was established, and good performance and clinical practicability were confirmed. Additionally, using the GSE109211 dataset from the Gene Expression Omnibus database, we were able to verify that the nine genes in this MRG signature had different responses to sorafenib, suggesting that some of these MRGs may act as therapeutic targets for HCC. CONCLUSIONS: We believe that these findings will add value in terms of the diagnosis, treatment, and prognosis of HCC.

The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers.

Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers. However, the functions of the many variants of these proteins in cancer remain incompletely understood. In this work, we used the most comprehensive database available, including more than 10000 samples across more than 30 tumor types, to analyze the six members of the netrin family. We performed comprehensive analysis of genetic change and expression of the netrin genes and analyzed epigenetic and pathway relationships, as well as the correlation of expression of these proteins with drug sensitivity. Although the mutation rate of the netrin family is low in pan-cancer, among the tumor patients with netrin mutations, the highest number are Uterine Corpus Endometrial Carcinoma patients, accounting for 13.6% of cases (54 of 397). Interestingly, the highest mutation rate of a netrin family member is 38% for NTNG1 (152 of 397). Netrin proteins may participate in the development of endocrine-related tumors and sex hormone-targeting organ tumors. Additionally, the participation of NTNG1 and NTNG2 in various cancers shows their potential for use as new tumor markers and therapeutic targets. This analysis provides a broad molecular perspective of this protein family and suggests some new directions for the treatment of cancer.

Identification of biomarkers related to CD8+ T cell infiltration with gene co-expression network in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an extremely common kind of kidney cancer in adults. Immunotherapy and targeted therapy are particularly effective at treating ccRCC. In this study, weighted gene co-expression network analysis and a deconvolution algorithm that quantifies the cellular composition of immune cells were used to analyze ccRCC expression data from the Gene Expression Omnibus database, and identify modules related to CD8+ T cells. Ten hub genes (LCK, CD2, CD3D, CD3G, IRF1, IFNG, CCR5, CD8A, CCL5, and CXCL9) were identified by co-expression network and protein-protein interactions network analysis. Datasets obtained from The Cancer Genome Atlas were analyzed and the data revealed that the hub genes were meaningfully up-regulated in tumor tissues and correlated with promotion of tumor progression. After Kaplan-Meier analysis and Oncomine meta-analysis, CCL5 was selected as a prognostic biomarker. Finally, the experimental results show that reduced expression of CCL5 decreased cell proliferation and invasion in the ccRCC cell line. Various analyses were performed and verified, CCL5 is a potential biomarker and therapeutic target which related to CD8+ T cell infiltration in ccRCC.

Overexpression of microRNA-301b accelerates hippocampal microglia activation and cognitive impairment in mice with depressive-like behavior through the NF-κB signaling pathway.

Depression is a condition with a complex etiological pattern, whose effective treatments are highly limited. MicroRNAs (miRNAs) have been investigated in intensive studies owing to their involvement in pathophysiology of mood disorders. The current study aimed to elucidate the role of miR-301b in hippocampus in mouse models of depressive-like behavior. Microarray-based prediction identified the differentially expressed gene neuronal pentraxin II (NPTX2) related to mental depression. Next, the putative miR-301b binding sites on the 3'UTR of NPTX2 were verified. Then the effect of miR-301b on cognitive function of mice with depressive-like behavior was analyzed using the Morris water maze test. In addition, the regulation of miR-301b to NPTX2 and activation of NF-κB signaling pathway was assessed. Following that, the microglia activation and inflammation in hippocampus were evaluated, with the expressions of inflammatory factors being examined. At last, microglia were flow cytometrically sorted and the inflammatory reaction was also assessed in vitro. The obtained findings revealed that miR-301b targeted and negatively regulated NPTX2. Moreover, overexpressed miR-301b activated the NF-κB signaling pathway, as reflected by increasing protein expressions of p-NF-κB. Upregulated miR-301b accelerated cognitive impairment in mice with depressive-like behavior. In addition, overexpression of miR-301b activated microglia and stimulated inflammation in hippocampus, accompanied by enhanced release of tumor necrosis factor-α (TNF-α), interleukin-Iß (IL-Iß) and cyclooxygenase-2(COX-2). Taken together, the evidence provided by the current study indicated that overexpression of miR-301b augmented hippocampal microglia activation, thus exacerbating cognitive impairment and inflammation in mice with depressive-like behavior by activating the NF-κB signaling pathway.

Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-ß1 signaling pathway.

Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR-192-5p and its target gene fibulin (Fbln)-2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)-induced depression through regulation of the TGF-ß1 signal transduction pathway. Verification of the targeting relationship between miR-192-5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual-luciferase reporter gene assay. Normal mice and models induced by CUMS were assigned into various groups, whereas mimics, inhibitors, and small interfering RNA were introduced to validate the regulatory mechanism by which miR-192-5p regulates Fbln2 depression. Novel object recognition, tail suspension testing, and Morris water maze were all employed 28 d after transfection. Hippocampal electrophysiological recordings, Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry were performed to further evaluate cognitive function and neuron regeneration. CUMS-induced depression was determined to represent a predisposing factor for cognitive impairment and damage to neural function in mice, highlighted by novel object recognition, learning and memory abilities, population spike amplitude, synaptic transmission, cAMP levels, neuronal regeneration, and increased behavioral changes that resemble depression. Furthermore, increased Fbln2 expression, an activated TGF-ß1 signaling pathway, and decreased expression of miR-192-5p, synaptophysin, brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, and calmodulin-dependent protein kinase II were noted. Up-regulated miR-192-5p targeting Fbln2 acts to alleviate CUMS-induced depression by inhibiting the TGF-ß1 signaling pathway, resulting in the enhanced cognitive function in novel object recognition, learning and memory ability, population spike amplitude, synaptic transmission, neuron regeneration, and alleviation of behavioral symptoms. The central findings of the present study indicate that up-regulated levels of miR-192-5p expression act to suppress activation of the TGF-ß1 signaling pathway by means of binding to Fbln2, thereby ameliorating cognitive impairment and strengthening neural function in a mouse model of depression.-Tang, C.-Z., Yang, J.-T., Liu, Q.-H., Wang, Y.-R., Wang, W.-S. Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-ß1 signaling pathway.

Elevated Serum Levels of Neopterin at Admission Predicts Depression After Acute Ischemic Stroke: a 6-Month Follow-Up Study.

Inflammation and cell-mediated immune activation are attributed to the pathogenesis and pathophysiology in depression. Our aim was to test the possible association between serum levels of neopterin and the development of post-stroke depression (PSD) in Chinese patients. The subjects were first-ever acute ischemic stroke patients who were hospitalized at the First Affiliated Hospital of Xinxiang Medical University during the period from December 2012 to December 2013. Clinical information and stroke severity were collected at admission. Neurological and neuropsychological evaluations were conducted at the 6-month follow-up. Serum neopterin levels were measured using fluorometry and a high performance liquid chromatography (HPLC) method. Multivariate analyses were performed using logistic regression models. During the study period, 226 patients were included and finished the 6-month follow-up. Sixty-nine patients (30.5 %) were diagnosed as having major depression at 6 months. Patients with major depression showed higher levels of serum neopterin (21.6[IQR, 18.9-25.7]nmol/L vs. 14.6[IQR, 12.2-18.4]nmol/L, P < 0.0001) at admission. In multivariate analyses, serum neopterin was an independent predictor of PSD at 6 months [odds ratio (OR): 1.952 (95 % CI, 1.358-2.805), P < 0.0001]. With an AUC of 0.850 (95 % CI, 0.797-0.902), neopterin showed a significantly greater discriminatory ability as compared with high-sensitivity C-reactive protein, age, body mass index, and National Institutes of Health and Stroke Scale score. Neopterin is a novel, independent predictor of the development of depression 6 months after stroke. This indicated that the elevated neopterin levels may play a significant role in the pathology of depression and that the pathways leading to inflammation and cell-mediated immune activation warrant further exploration.

Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels.

Inflammatory processes have fundamental roles in depression. The primary purpose of this study was to assess the serum levels of high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) at admission to the presence of poststroke depression (PSD). From December 2012 to December 2013, first-ever acute ischemic stroke patients who were admitted to the hospital within the first 24 h after stroke onset were consecutively recruited and followed up for 6 months. Serum levels of Hs-CRP and HCY were tested at admission. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression at 6 months after stroke. Ninety-five patients (42.0%) showed depression (major + minor) at 6 months after admission, and in 69 patients (30.5%), this depression was classified as major. In the 69 patients with major depression, our results showed significantly higher Hs-CRP and HCY levels at admission than patients without major depression. After adjusting all other possible covariates, Hs-CRP and HCY still were independent predicators of PSD with adjusted OR of 1.332 (95% CI, 1.230-1.452; P < 0.001) and 1.138 (95% CI, 1.072-1.274; P < 0.001), respectively. The area under the receiver operating characteristic curve values of Hs-CRP and HCY were 0.765 (95% CI, 0.701-0.9825) and 0.684 (95% CI, 0.610-0.757) for PSD, respectively. The prognostic accuracy of combined model (HCY and Hs-CRP) was higher compared to those biomarkers alone and other markers. Elevated serum levels of Hs-CRP and HCY at admission were found to be associated with depression 6 months after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.

The complete mitochondrial genome of Bos gaurus gon-shan (Bovidae; Bovinae).

In the present work we undertook the complete mitochondrial genome sequencing of a wild gon-shan chinese cattle Bos gaurus gon-shan. The total length of the mitogenome was 16,356 bp with the base composition of 33.4% for A, 27.2% for T, 26.0% for C, and 13.4% for G and an A-T (60.6%)-rich feature was detected. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and one non-coding control region (D-loop region). The arrangement of all genes was identical to the typical mitochondrial genomes of cattle.