Spray-Assisted Interfacial Polymerization to Form CuII/I@CMC-PANI Film: An Efficient Dip Catalyst for A3 Reaction.

A novel and interesting method for the preparation of carboxymethylcellulose-polyaniline film-supported copper catalyst (CuII/I@CMC-PANI) has been developed via spray-assisted interfacial polymerization. Using copper sulfate as an initiator, spraying technology was introduced to form a unique interface that is perfectly beneficial to the polymerization of aniline monomers onto carboxymethylcellulose macromolecule chains. To further confirm the composition and structure of the as-prepared hybrid film, it was systematically characterized by inductively coupled plasma (ICP), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and thermogravimetric analysis (TGA) techniques. The Cu content in the fresh CuII/I@CMC-PANI film was determined to be 1.805 mmol/g, and spherical nanoparticles with an average size of ca. 10.04 nm could be observed in the hybrid film. The CuII/I@CMC-PANI hybrid film was exerted as a dip catalyst to catalyze the aldehyde-alkyne-amine (A3) coupling reactions. High yields of the products (up to 97%) were obtained in this catalytic system, and the catalyst could be easily picked up from the reaction mixture by tweezers and reused for at least six consecutive runs, without any discernible losses in its activity in the model reaction. The dip catalyst of CuII/I@CMC-PANI, with easy fabrication, convenient deployment, superior catalytic activity, and great reusability, is expected to be very useful in organic synthesis.

Systematic evaluation of the prognostic and immunological role of PDLIM2 across 33 cancer types.

The protein PDLIM2 regulates the stability of various transcription factors and is required for polarized cell migration. However, the clinical relevance and immune infiltration of PDLIM2 in cancer are not well-understood. We utilized The Cancer Genome Atlas and Genotype-Tissue Expression database to characterize alterations in PDLIM2 in pan-cancer. TIMER was used to explore PDLIM2 expression and immune infiltration levels. We assessed the correlation between PDLIM2 expression and immune-associated gene expression, immune score, tumor mutation burden, and DNA microsatellite instability. PDLIM2 significantly affected the prognosis of various cancers. Increased expression of PDLIM2 was significantly correlated with the tumor grade in seven types of tumors. The expression level of PDLIM2 was positively correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells in bladder urothelial, kidney renal papillary cell, and colon adenocarcinoma. High expression levels of PDLIM2 tended to be associated with higher immune and stromal scores. PDLIM2 expression was associated with the tumor mutation burden in 12 cancer types and microsatellite instability in 5 cancer types. PDLIM2 levels were strongly correlated with diverse immune-related genes. PDLIM2 can act as a prognostic-related therapeutic target and is correlated with immune infiltrates in pan-cancer.

Prognostic and Immunological Roles of MMP-9 in Pan-Cancer.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) can degrade the extracellular matrix and participate in tumor progression. The relationship between MMP-9 and immune cells has been reported in various malignant tumors. However, there is a lack of comprehensive pan-cancer studies on the relationship between MMP-9 and cancer prognosis and immune infiltration. METHOD: We used data from TCGA and GTEx databases to comprehensively analyze the differential expression of MMP-9 in normal and cancerous tissues. Survival analysis was performed to understand the prognostic role of MMP-9 in different tumors. We then analyzed the expression of MMP-9 across different tumors and at different clinical stages. Based on the results, we assessed the correlation between MMP-9 expression and immune-associated genes and immunocytes. Finally, we calculated the tumor mutation burden (TMB) of 33 cancer types and analyzed the correlation between MMP-9 and TMB, DNA microsatellite instability, and DNA repair genes. RESULTS: MMP-9 significantly affected the prognosis and metastasis of various cancers. It was associated based on overall survival, disease-specific survival in five tumors, progression-free interval in seven tumors, and clinical stage in eight tumors, as well as with prognosis and metastasis in adrenocortical carcinoma and kidney renal clear cell carcinoma. It was also coexpressed with immune-related genes and DNA repair genes. The expression of MMP-9 was positively correlated with the markers of T cells, tumor-associated macrophages, Th1 cells, and T cell exhaustion. Furthermore, MMP-9 expression was highly correlated with macrophage M0 in 28 tumors. In addition, its expression was associated with TMB in eight cancer types and DNA microsatellite instability in six cancer types. CONCLUSION: MMP-9 is related to immune infiltration in pan-cancer and can be used as a biomarker related to cancer prognosis and metastasis. Our findings provide prognostic molecular markers and new ideas for immunotherapy.

Study on the Mechanism of Liuwei Dihuang Pills in Treating Parkinson's Disease Based on Network Pharmacology.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Liuwei Dihuang (LWDH) pills have a good effect on PD, but its mechanism remains unclear. Network pharmacology is the result of integrating basic theories and research methods of medicine, biology, computer science, bioinformatics, and other disciplines, which can systematically and comprehensively reflect the mechanism of drug intervention in disease networks. METHODS: The main components and targets of herbs in LWDH pills were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Its active components were screened based on absorption, distribution, metabolism, and excretion (ADME); the PD-related targets were obtained from the Genecards, OMIM, TTD, and DRUGBANK databases. We used R to take the intersection of LWDH- and PD-related targets and Cytoscape software to construct the drug-component-target network. Moreover, STRING and Cytoscape software was used to analyze protein-protein interactions (PPI), construct a PPI network, and explore potential protein functional modules in the network. The Metascape platform was used to perform KEGG pathway and GO function enrichment analyses. Finally, molecular docking was performed to verify whether the compound and target have good binding activity. RESULTS: After screening and deduplication, 210 effective active ingredients, 204 drug targets, 4333 disease targets, and 162 drug-disease targets were obtained. We consequently constructed a drug-component-targets network and a PPI-drug-disease-targets network. The results showed that the hub components of LWDH pills were quercetin, stigmasterol, kaempferol, and beta-sitosterol; the hub targets were AKT1, VEGFA, and IL6. GO and KEGG enrichment analyses showed that these targets are involved in neuronal death, G protein-coupled amine receptor activity, reactive oxygen species metabolic processes, membrane rafts, MAPK signaling pathways, cellular senescence, and other biological processes. Molecular docking showed that the hub components were in good agreement with the hub targets. CONCLUSION: LWDH pills have implications for the treatment of PD since they contain several active components, target multiple ligands, and activate various pathways. The hub components possibly include quercetin, stigmasterol, kaempferol, and beta-sitosterol and act through pairing with hub targets, such as AKT1, VEGFA, and IL6, to regulate neuronal death, G protein-coupled amine receptor activity, reactive oxygen species metabolic process, membrane raft, MAPK signaling pathway, and cellular senescence for the treatment of PD.

Plasma Metabolomics Profiling of Metabolic Pathways Affected by Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a common disease which is complicated by metabolic disorder. Although MDD has been studied relatively intensively, its metabolism is yet to be elucidated. Methods: To profile the global pathophysiological processes of MDD patients, we used metabolomics to identify differential metabolites and applied a new database Metabolite set enrichment analysis (MSEA) to discover dysfunctions of metabolic pathways of this disease. Hydrophilic metabolomics were applied to identify metabolites by profiling the plasma from 55 MDD patients and 100 sex-, gender-, BMI-matched healthy controls. The metabolites were then analyzed in MSEA in an attempt to discover different metabolic pathways. To investigate dysregulated pathways, we further divided MDD patients into two cohorts: (1) MDD patients with anxiety symptoms and (2) MDD patients without anxiety symptoms. Results: Metabolites which were hit in those pathways correlated with depressive and anxiety symptoms. Altogether, 17 metabolic pathways were enriched in MDD patients, and 23 metabolites were hit in those pathways. Three metabolic pathways were enriched in MDD patients without anxiety, including glycine and serine metabolism, arginine and proline metabolism, and phenylalanine and tyrosine metabolism. In addition, L-glutamic acid was positively correlated with the severity of depression and retardation if hit in MDD patients without anxiety symptoms. Conclusions: Different kinds of metabolic pathophysiological processes were found in MDD patients. Disorder of glycine and serine metabolism was observed in both MDD patients with anxiety and those without.

Plasma metabolites were associated with spatial working memory in major depressive disorder.

ABSTRACT: Major depressive disorder (MDD) is a common disease with both affective and cognitive disorders. Alterations in metabolic systems of MDD patients have been reported, but the underlying mechanisms still remains unclear. We sought to identify abnormal metabolites in MDD by metabolomics and to explore the association between differential metabolites and neurocognitive dysfunction.Plasma samples from 53 MDD patients and 83 sex-, gender-, BMI-matched healthy controls (HCs) were collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was then used to detect metabolites in those samples. Two different algorithms were applied to identify differential metabolites in 2 groups. Of the 136 participants, 35 MDD patients and 48 HCs had completed spatial working memory test. Spearman rank correlation coefficient was applied to explore the relationship between differential metabolites and working memory in these 2 groups.The top 5 metabolites which were found in sparse partial least squares-discriminant analysis (sPLS-DA) model and random forest (RF) model were the same, and significant difference was found in 3 metabolites between MDD and HCs, namely, gamma-glutamyl leucine, leucine-enkephalin, and valeric acid. In addition, MDD patients had higher scores in spatial working memory (SWM) between errors and total errors than HCs. Valeric acid was positively correlated with working memory in MDD group.Gamma-glutamyl leucine, leucine-enkephalin, and valeric acid were preliminarily proven to be decreased in MDD patients. In addition, MDD patients performed worse in working memory than HCs. Dysfunction in working memory of MDD individuals was associated with valeric acid.

Densification and Phase Transformation in Multi-Layered Graded Si3N4-TiN Components Produced by Field-Assisted Sintering.

The structural and/or functional design of multiphase ceramics, along with their processing, are timely research topics in the area of field-assisted sintering techniques, such as spark plasma sintering, especially for systems containing both electrically insulating and conductive phases. In the present study, spark plasma sintering of Si3N4-TiN composites was investigated by changing the TiN particle size and electrical current waveform. Their combined effects on both the densification behavior and α-to-ß phase conversion of the Si3N4 matrix was studied and compared by means of a thermodynamic approach and dilatometric measurements. Through the control of TiN phase characteristics and heating mode, double-layered Si3N4-based components were also prepared using a one-step spark plasma sintering process, which was compared with conventional hot-pressing. It was shown that the size of the conductive TiN phase has a significant influence on the particle rearrangement, with the formation of a liquid phase, and the solution-diffusion-precipitation process, through the field-induced local heating and electrowetting mechanisms. Moreover, the contribution of current pulsing to the densification and α-to-ß conversion of the layered Si3N4-based components was mostly dependent upon the particle size distribution and content of the TiN phase, indicating that the electric-field effect is dependent upon current path.

Increased expression of a novel miRNA in peripheral blood is negatively correlated with hippocampal volume in patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a serious psychiatric illness with unclear pathophysiology. As one of the post-transcriptional regulators, prior research has indicated that miRNAs are involved in the pathophysiology of MDD. The aim of this study was to screen the MDD-related miRNAs in the peripheral blood and investigate the target genes of the differentially expressed miRNAs and their potential functions in MDD pathophysiology. METHODS: miRNA sequencing was performed using the peripheral blood of patients with MDD and matched controls (cohort A, 10 vs 10). The nominal significant results were validated in an independent sample (cohort B, 72 vs 75) by real-time quantitative polymerase chain reaction (PCR). The target genes of verified miRNAs were predicted using Miranda software. Luciferase assay was used to verify one of the predicted target genes. Furthermore, we analyzed the correlations between the expression of pmiR-chr11 and hippocampal volume. RESULTS: Ten miRNAs were nominally significantly dysregulated in patients with MDD in cohort A. One of the 10 miRNAs, pmiR-chr11, was significantly dysregulated in cohort B. The pmiR-chr11 could regulate one of the target genes, BRPF1 (bromodomain and PHD finger containing 1), via binding its 3' untranslated region (UTR). The expression of pmiR-chr11 was negatively correlated with hippocampal volume in patients with MDD. LIMITATIONS: The expression of the miRNAs and mRNAs detected in the peripheral blood may not reflect the expression in the brain. CONCLUSIONS: Our findings suggested that the pmiR-chr11 may influence hippocampal volume by regulating BRPF1 in MDD.

Predictive markers of depression in hypertension.

Hypertension and depression, as 2 major public health issues, are closely related. For patients having hypertension, in particular, depression is a risk factor for mortality and jeopardizes their wellbeing. The aim of the study is to apply support vector machine (SVM) learning to blood tests and vital signs to classify patients having hypertension complicated by depression and patients having hypertension alone for the identification of novel markers.Data on patients having both hypertension and depression (n = 147) and patients having hypertension alone (n = 147) were obtained from electronic medical records of admissions containing the records on blood tests and vital signs. Using SVM, we distinguished patients having both hypertension and depression from gender- and age-matched patients having hypertension alone.SVM-based classification achieved 73.5% accuracy by 10-fold cross-validation between patients having both hypertension and depression and those having hypertension alone. Twelve features were selected to compose the optimal feature sets, including body temperature (T), glucose (GLU), creatine kinase (CK), albumin (ALB), hydroxybutyrate dehydrogenase (HBDH), blood urea nitrogen (BUN), uric Acid (UA), creatinine (Crea), cholesterol (TC), total protein (TP), pulse (P), and respiration (R).SVM can be used to distinguish patients having both hypertension and depression from those having hypertension alone. A significant association was identified between depression and blood tests and vital signs. This approach can be helpful for clinical diagnosis of depression, but further studies are needed to verify the role of these candidate markers for depression diagnosis.

Gray matter volume abnormalities were associated with sustained attention in unmedicated major depression.

BACKGROUND: Impaired sustained attention seems to be a core feature of depression while the anatomical alteration of brain was widely reported in depression patients. The authors aimed to identify the relationship between anatomical brain changes and sustained attention deficits in unmedicated patients with major depressive disorder (MDD). METHODS: A total of 51 medication-free MDD patients and 51 matched healthy controls (HC) underwent high-resolution structural magnetic resonance imaging scanning, and optimized voxel-based morphometry method was performed to analyze the changes of gray matter volume (GMV). We employed a computerized neurocognitive task from the Cambridge Neuropsychological Tests Automated Battery (CANTAB)--Rapid Visual Information Processing (RVP) task--as a measurement of sustained attention. Based on clinical symptoms, 40 patients who had completed CANTAB-RVP test were divided into MDDa (mild depression patients) and MDDb (severe depression patients) groups. Then the relationships among sustained attention, GMV of different regions and clinical symptoms were explored separately. RESULTS: MDD patients showed significant GMV increase in left posterior cingulate cortex (PCC) and inferior frontal gyrus (IFG) (p<0.001, uncorrected), and significant GMV decrease in medial/superior frontal gyrus (MFG/SFG) and lingual gyrus (p<0.001, uncorrected). Structure-cognition correlation analyses revealed that in MDD patients, GMV alterations of the IFG were significantly correlated with sustained attention as measured by the CANTAB-RVP. CONCLUSIONS: Increased GMV values of IFG were associated with sustained attention which may underlie the pathophysiology of MDD or be part of the cognition circuit. In the severe depression patients, sustained attention deficits were positively correlated with clinical symptoms.

Analysis of hair cortisol level in first-episodic and recurrent female patients with depression compared to healthy controls.

BACKGROUND: Although accumulating evidence has shown increased cortisol levels in serum, saliva, or 24-h urine samples in depression, a number of studies did not find the association between cortisol levels and depression. Hair cortisol levels reflect long-term and historical information of cortisol and hair cortisol analysis has been applied in the research of psychiatric diseases. The aim of this study is to compare the hair cortisol levels between patients with depression and healthy controls. METHODS: Hair cortisol levels of 22 first-episodic and 13 recurrent female patients with depression and 30 healthy controls were measured and compared using the electrochemiluminescence immunoassay. The relationship between hair cortisol levels and Hamilton depression scale (HAMD) or Hamilton anxiety scale (HAMA) scores were also examined. RESULTS: Before disease episode, no significant differences were observed among healthy controls, first-episodic patients and recurrent patients. In disease episode, the hair cortisol level in first-episodic patients was significantly higher than that in healthy controls or recurrent patients, while no significant difference was observed between recurrent patients and healthy controls. No significant correlation was found between HAMD or HAMA scores and hair cortisol levels in patients. LIMITATIONS: First, long-term effects of antidepressants on the results cannot be excluded without detailed medication information of the recurrent patients. Second, sample sizes might be relatively small. CONCLUSIONS: Our results indicate that hair cortisol levels increased in disease episode in first-episodic, but not recurrent patients with depression, which may suggest that episodes of disease have influence on cortisol levels.

Association study of dopamine receptor genes polymorphism with cognitive functions in bipolar I disorder patients.

OBJECTIVE: To determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD. METHODS: Twenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education. RESULTS: The allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ(2)=9.386, Corrected P=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ(2)=9.27, Corrected P=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (ß=3.20 and Corrected P=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (ß=2.80 and Corrected P=0.017). The genotypic association analyses also supported the findings (F=4.24 and P=0.007), but this effect was not found in controls. LIMITATIONS: The sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion. CONCLUSIONS: DRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.

Hair thyroid hormones concentration in patients with depression changes with disease episodes in female Chinese.

Abnormal function of thyroid and deregulation of level of blood thyroid hormones, including triiodothyronine (T3) and thyroxine (T4), have been observed in patients with major depression. Nevertheless, no consistent conclusion can be drawn from previous reports. Hair hormones reflect average hormones levels in a certain period and have been involved in the studies of psychiatric diseases. However, no research has elucidated the relation between hair thyroid hormones level and depression. In the present study, we explored the correlation between thyroid hormones and major depression by analyzing and comparing the levels of hair thyroid hormones in patients with depression (n=30) and healthy controls (n=30). Our results showed that the levels of hair T3 and T4 were significantly lower in patients with depression in disease episode than that in pre-disease episode or in healthy controls. Moreover, patients with depression in pre-disease episode had a higher hair T4 level than healthy controls. No significant correlation was observed between hair T3 or T4 levels and the Hamilton depression rating scale and Hamilton anxiety rating scale scores. Our results indicate that hair thyroid hormones levels change with the episodes of depressions, which may be helpful for pathological studies of depression.

Role of psychosocial factors and serotonin transporter genotype in male adolescent criminal activity.

INTRODUCTION: Violent behavior is influenced by various environmental factors and the serotonergic circuitry alike. Nevertheless, studies on relations among genes, personality, social environment, and juvenile violent behavior are limited, and there is no such study in China. METHODS: In the current study, we aimed to investigate the contribution of serotonin transporter (5-HTT) polymorphisms to the development of violence and to explore the relations among genes, personality, social environment, and juvenile violent behavior in China. We recruited 213 male adolescents with violent crime history and 145 male adolescents without violent crime history. The association between each risk factor and violent behavior for all the participants was examined, and the interrelation of the domains (personality, family, social support, coping style, impulsivity, and aggression) and the adolescents' violent behavior was analyzed. Chi-square test was used to examine the association between genotypes and violent behavior. RESULTS: Adolescents with a violent crime history had lower education levels, higher neuroticism and psychoticism, but lower dissimulate. Social support and coping style were significantly associated with their criminal behaviors. DISCUSSION: The 5-HTTLPR genotype distributions differed significantly between the violent and nonviolent groups.