Hypoxia inducible factor-1α regulates microglial innate immune memory and the pathology of Parkinson's disease.

Neuroinflammation is one of the core pathological features of Parkinson's disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate immune memory, resulting in an enhanced or suppressed immune response to second stimuli, which is known as innate immune training and innate immune tolerance, respectively. In this study, LPS was used to establish in vitro and in vivo models of innate immune memory. Microglia-specific Hif-1α knockout mice were further employed to elucidate the regulatory role of HIF-1α in innate immune memory and MPTP-induced PD pathology. Our results showed that different paradigms of LPS could induce innate immune training or tolerance in the nigrostriatal pathway of mice. We found that innate immune tolerance lasting for one month protected the dopaminergic system in PD mice, whereas the effect of innate immune training was limited. Deficiency of HIF-1α in microglia impeded the formation of innate immune memory and exerted protective effects in MPTP-intoxicated mice by suppressing neuroinflammation. Therefore, HIF-1α is essential for microglial innate immune memory and can promote neuroinflammation associated with PD.

Actinoplanes sandaracinus sp. nov., a novel ligninase- producing and cellulose-degrading actinobacterium isolated from soil.

A novel ligninase-producing and cellulose-degrading actinobacterium, designated strain NEAU-A12T, was isolated from a soil sample collected from Aohan banner, Chifeng City, Inner Mongolia Autonomous Region, PR China. A polyphasic taxonomic study was used to establish the status of strain NEAU-A12T. 16S rRNA gene sequence analysis revealed that strain NEAU-A12T belonged to the genus Actinoplanes and showed the highest similarity (98.3 %) to Actinoplanes palleronii DSM 43940T, while showing less than 98.3 % similarity to other members of the genus Actinoplanes. The phospholipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and glycosylphosphatidylinositol. The diagnostic sugars in cell hydrolysates were determined to be arabinose, glucose and xylose. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The major fatty acids were C15 : 0, C16 : 0, C16 : 1 ω7c and C17 : 0. Meanwhile, genomic analysis revealed a genome size of 10 192 524 bp and a DNA G+C content of 70.6 mol%, and indicated that strain NEAU-A12T had the potential to degrade lignin and cellulose, as well as produce bioactive compounds. In addition, the average nucleotide identity values between strain NEAU-A12T and its reference strains A. palleronii DSM 43940T, Actinoplanes regularis DSM 43151T, Actinoplanes philippinensis DSM 43019T, Actinoplanes xinjiangensis DSM 45184T and Actinoplanes italicus DSM 43146T were 80.3, 80.3, 84.1, 84.3 and 84.0 %, respectively. The levels of digital DNA-DNA hybridization between them were found to be 23.6 % (21.3-26.1 %), 23.8 % (21.5-26.3 %), 28.3 % (25.9-30.8 %), 28.6 % (26.0-30.9 %) and 28.4 % (26.2-31.1 %), respectively. Based on phenotypic, chemotaxonomic and genotypic data, strain NEAU-A12T is considered to represent a novel species of the genus Actinoplanes, for which the name Actinoplanes sandaracinus sp. nov. is proposed, with NEAU-A12T (=CCTCC AA 2020039T=DSM 112043T) as the type strain.

A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis.

Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.

Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity.

Emerging evidence suggests that DNA methylation affects transcriptional regulation and expression perturbations of long non-coding RNAs (lncRNAs) in cancer. However, a comprehensive investigation into the transcriptional control of DNA methylation-mediated dysregulation of transcription factors (TFs) on lncRNAs has been lacking. Here, we integrated the transcriptome, methylome, and regulatome across 21 human cancers and systematically identified the transcriptional regulation of DNA methylation-mediated TF dysregulations (DMTDs) on lncRNAs. Our findings reveal that TF regulation of lncRNAs is significantly impacted by DNA methylation. Comparative analysis of DMTDs on mRNAs revealed a conserved pattern of TFs involvement. Pan-cancer Methylation TFs (MethTFs) and Methylation LncRNAs (MethLncRNAs) were identified, and were found to be closely associated with cancer hallmarks and clinical features. In-depth analysis of co-expressed mRNAs with pan-cancer MethLncRNAs unveiled frequent disruptions in cancer immunity, particularly in the context of inflammatory response. Furthermore, we identified five immune-related network modules that contribute to immune cell infiltration in cancer. Immune-related subtypes were subsequently classified, characterized by high levels of immune cell infiltration, expression of immunomodulatory genes, and relevant immune cytolytic activity score, major histocompatibility complex score, response to chemotherapy, and prognosis. Our findings provide valuable insights into cancer immunity from the epigenetic and transcriptional regulation perspective.

An Improved Canonical Correlation Analysis for EEG Inter-Band Correlation Extraction.

(1) Background: Emotion recognition based on EEG signals is a rapidly growing and promising research field in affective computing. However, traditional methods have focused on single-channel features that reflect time-domain or frequency-domain information of the EEG, as well as bi-channel features that reveal channel-wise relationships across brain regions. Despite these efforts, the mechanism of mutual interactions between EEG rhythms under different emotional expressions remains largely unexplored. Currently, the primary form of information interaction between EEG rhythms is phase-amplitude coupling (PAC), which results in computational complexity and high computational cost. (2) Methods: To address this issue, we proposed a method of extracting inter-bands correlation (IBC) features via canonical correlation analysis (CCA) based on differential entropy (DE) features. This approach eliminates the need for surrogate testing and reduces computational complexity. (3) Results: Our experiments verified the effectiveness of IBC features through several tests, demonstrating that the more correlated features between EEG frequency bands contribute more to emotion classification accuracy. We then fused IBC features and traditional DE features at the decision level, which significantly improved the accuracy of emotion recognition on the SEED dataset and the local CUMULATE dataset compared to using a single feature alone. (4) Conclusions: These findings suggest that IBC features are a promising approach to promoting emotion recognition accuracy. By exploring the mutual interactions between EEG rhythms under different emotional expressions, our method can provide valuable insights into the underlying mechanisms of emotion processing and improve the performance of emotion recognition systems.

NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson's disease models.

Parkinson's disease (PD) is mainly characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and neuroinflammation mediated by overactivated microglia and astrocytes. NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) has been reported to participate in various immune disorders, but its role in neurodegenerative diseases remains unclear. In the current study, we found that the expression of NLRC5 was increased in the nigrostriatal axis of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD, as well as in primary astrocytes, microglia and neurons exposed to different neurotoxic stimuli. In an acute MPTP-induced PD model, NLRC5 deficiency significantly reduced dopaminergic system degeneration and ameliorated motor deficits and striatal inflammation. Furthermore, we found that NLRC5 deficiency decreased the expression of the proinflammatory genes IL-1ß, IL-6, TNF-α and COX2 in primary microglia and primary astrocytes treated with neuroinflammatory stimuli and reduced the inflammatory response in mixed glial cells in response to LPS treatment. Moreover, NLRC5 deficiency suppressed activation of the NF-κB and MAPK signaling pathways and enhanced the activation of AKT-GSK-3ß and AMPK signaling in mixed glial cells. Furthermore, NLRC5 deficiency increased the survival of primary neurons treated with MPP+ or conditioned medium from LPS-stimulated mixed glial cells and promoted activation of the NF-κB and AKT signaling pathways. Moreover, the mRNA expression of NLRC5 was decreased in the blood of PD patients compared to healthy subjects. Therefore, we suggest that NLRC5 promotes neuroinflammation and dopaminergic degeneration in PD and may serve as a marker of glial activation.

Effect of vascular endothelial growth factor rs35569394 in esophageal cancer and response to chemotherapy.

The objective of this study was to investigate the possible association between the single nucleotide polymorphism (SNP), rs35569394, of the vascular endothelial growth factor gene (VEGF) and the risk of esophageal cancer (EC) in the Han Chinese population. A total of 290 EC subjects and 322 ethnically matched unrelated healthy controls free from the esophageal disease were studied. Genomic DNA was isolated from peripheral blood by salting out. Genotyping of VEGF rs35569394 polymorphism was carried out via polymerase chain reaction followed by agarose gel electrophoresis. The results showed that the distribution of genotypes was significantly different across the gender groups (p=0.032) and clinical stages (p=0.034). VEGF rs35569394 was associated with EC risk (p= 0.012, OR=1.34). A gender analysis break-down showed that rs35569394-D allele frequency was significantly higher in females than in the controls (p=0.0004, OR=1.81). Moreover, significant associations were also found in females under the dominant model (II versus ID+DD: χ2=8.18, p=0.003, OR=2.12) and the recessive model (II+ID versus DD: χ2=8.25, p=0.004, OR=2.39). Additionally, we found that the genotype, rs35569394-DD, was associated with a complete response + partial response to chemotherapy when compared with rs35569394-II (χ2=4.67, p=0.030, OR=0.47). In conclusion, our case-control study showed that the VEGF rs35569394 was significantly associated with the clinical stages and the increased risk of EC in Han Chinese females. In addition, the genotype rs35569394-DD showed a better response to chemotherapy.

NRSF regulates age-dependently cognitive ability and its conditional knockout in APP/PS1 mice moderately alters AD-like pathology.

NRSF/REST (neuron-restrictive silencer element, also known as repressor element 1-silencing transcription factor), plays a key role in neuronal homeostasis as a transcriptional repressor of neuronal genes. NRSF/REST relates to cognitive preservation and longevity of humans, but its specific functions in age-dependent and Alzheimer's disease (AD)-related memory deficits remain unclear. Here, we show that conditional NRSF/REST knockout either in the dorsal telencephalon or specially in neurons induced an age-dependently diminished retrieval performance in spatial or fear conditioning memory tasks and altered hippocampal synaptic transmission and activity-dependent synaptic plasticity. The NRSF/REST deficient mice were also characterized by an increase of activated glial cells, complement C3 protein and the transcription factor C/EBPß in the cortex and hippocampus. Reduction of NRSF/REST by conditional depletion upregulated the activation of astrocytes in APP/PS1 mice, and increased the C3-positive glial cells, but did not alter the Aß loads and memory retrieval performances of 6- and 12-month-old APP/PS1 mice. Simultaneously, overexpression of NRSF/REST improved cognitive abilities of aged wild type, but not in AD mice. These findings demonstrated that NRSF/REST is essential for the preservation of memory performance and activity-dependent synaptic plasticity during aging and takes potential roles in the onset of age-related memory impairments. However, while altering the glial activation, NRSF/REST deficiency does not interfere with the Aß deposits and the electrophysiological and cognitive AD-like pathologies.

Saccharothrix luteola sp. nov., a novel cellulose-degrading actinobacterium isolated from soil and emended description of the genus Saccharothrix.

A novel cellulose-degrading actinobacterium, designated strain NEAU-S10T, was isolated from soil collected from Chifeng, Inner Mongolia Autonomous Region, PR China, and characterized using a polyphasic approach. Pairwise similarity of the 16S rRNA gene sequence showed that strain NEAU-S10T was a representative of Saccharothrix and was closely related to Saccharothrix carnea NEAU-yn17T (99.2 %), Saccharothrix saharensis SA152T (99.0 %), Saccharothrix texasensis DSM 44231T (98.5 %) and Saccharothrix xinjiangensis NBRC 101911T (98.5 %). Physiological and chemotaxonomic characteristics of the strain further supported its affiliation to the genus Saccharothrix. The whole-cell sugars contained galactose, ribose and mannose. The polar lipids contained diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The predominant menaquinones were MK-9(H0), MK-9(H2), MK-9(H4) and MK-10(H4). The major fatty acids were iso-C16 : 0, C16 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C17 : 0. The genomic DNA G+C content was 71.8 mol%. The levels of digital DNA-DNA hybridization between isolate and S. carnea NEAU-yn17T, S. saharensis SA152T and S. texasensis DSM 44231T were 40.1 % (37.6-42.6 %), 38.soap8 % (36.3-41.3 %) and 44.8 % (42.2-47.3 %) and the ANI values between them were determined to be 90.2, 89.8 and 91.7 %, the results indicated that strain NEAU-S10T could be distinguished from its reference strains. The assembled genome sequence of strain NEAU-S10T was found to be 10 305 394 bp long. The NCBI Prokaryotic Genome Annotation Pipeline (PGAP) revealed 8 994 protein-coding genes. Genomic analysis and Congo red staining test indicated that strain NEAU-S10T had the potential to degrade cellulose. The genomic and phenotypic results indicate that strain NEAU-S10T represents a novel species of the genus Saccharothrix, for which the name Saccharothrix luteola sp. nov. is proposed, with NEAU-S10T (=CCTCC AA 2020037T=JCM 34800T) as the type strain.

Nocardia rosealba sp. nov., a novel ligninase-producing Actinobacterium isolated from soil.

A novel ligninase-producing actinomycete, designated strain NEAU-G4T, was isolated from a soil sample and subjected to a polyphasic taxonomic study to establish its status. According to 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Nocardia, with the highest sequence similarity to Nocardia ignorata DSM 44496T (99.2 %). The whole-cell sugars contained galactose and arabinose. The amino acid of the cell wall was determined to be meso-diaminopimelic acid. The major fatty acids (>10 %) were C16 : 0, C18 : 1 ω9c, C18 : 0 and C16 : 1 ω7c. The predominant menaquinone was identified as MK-8(H6, ω-cycl). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. Strain NEAU-G4T had a draft genome size of 6 405 167 bp, annotated with 5815 protein-coding genes. The DNA G+C content was 67.6 mol%. Phylogenetic analysis using the 16S rRNA gene and whole-genome sequences showed that strain NEAU-G4T formed a stable phyletic line with N. ignorata DSM 44496T. The digital DNA-DNA hybridization and average nucleotide identity values between them were 63.7 % (60.8-66.5 %) and 95.5 %, respectively. Moreover, genomic analysis indicated that strain NEAU-G4T had the potential to degrade lignin and produce bioactive compounds. On the basis of genotypic analysis, physiological data, as well as phenotypic and chemotaxonomic characterizations, it is concluded that the organism be classified as representing a novel species of the genus Nocardia, for which the name Nocardia rosealba sp. nov. is proposed. The type strain is NEAU-G4T (=CCTCC AA 2020038T=DSM 111936T).

LncPep: A Resource of Translational Evidences for lncRNAs.

Long noncoding RNAs (lncRNAs) are a type of transcript that is >200 nucleotides long with no protein-coding capacity. Accumulating studies have suggested that lncRNAs contain open reading frames (ORFs) that encode peptides. Although several noncoding RNA-encoded peptide-related databases have been developed, most of them display only a small number of experimentally validated peptides, and resources focused on lncRNA-encoded peptides are still lacking. We used six types of evidence, coding potential assessment tool (CPAT), coding potential calculator v2.0 (CPC2), N6-methyladenosine modification of RNA sites (m6A), Pfam, ribosome profiling (Ribo-seq), and translation initiation sites (TISs), to evaluate the coding potential of 883,804 lncRNAs across 39 species. We constructed a comprehensive database of lncRNA-encoded peptides, LncPep (http://www.shenglilabs.com/LncPep/). LncPep provides three major functional modules: 1) user-friendly searching/browsing interface, 2) prediction and BLAST modules for exploring novel lncRNAs and peptides, and 3) annotations for lncRNAs, peptides and supporting evidence. Taken together, LncPep is a user-friendly and convenient platform for discovering and investigating peptides encoded by lncRNAs.

Computed tomography-guided coil localization for scapular-blocked lung nodules.

PURPOSE: To investigate the clinical efficacy, feasibility, and safety of the preoperative computed tomography (CT)-guided coil localization (CL) approach for scapula-blocked lung nodules (SBLNs). MATERIAL AND METHODS: A total of 123 patients with LNs were treated via CT-guided CL and subsequent VATS-guided wedge resection from January 2015 to June 2020. Of these patients, 12 (9.8%) exhibited SBLNs and underwent CT-guided CL. Technical success of localization and video-assisted thoracoscopic surgery (VATS)-guided wedge resection, and localization-related complications were recorded and analyzed. RESULTS: The technical success rate of CT-guided CL was 100%. Each patient was placed with one coil. The mean duration of CT-guided CL was 14.7 ± 2.7 min. One patient (8.3%) developed asymptomatic pneumothorax, which has not impacted the subsequent VATS procedure. Successful VATS-guided wedge resection of these SBLNs was achieved in all patients, with no instances of conversion to thoracotomy. Additional lobectomy was performed in three patients. The mean duration of the VATS procedure and blood loss were 143.8 ± 95.5 min and 110.0 ± 82.0 ml, respectively. CONCLUSIONS: The approach of CT-guided CL could be safely and easily utilized to facilitate high rates of success when conducting the VATS-guided wedge resection of SBLNs.

Identification of a Three-Gene Signature Based on Epithelial-Mesenchymal Transition of Lung Adenocarcinoma Through Construction and Validation of a Risk-Prediction Model.

Epithelial-mesenchymal transition (EMT) process, which is regulated by genes of inducible factors and transcription factor family of signaling pathways, transforms epithelial cells into mesenchymal cells and is involved in tumor invasion and progression and increases tumor tolerance to clinical interventions. This study constructed a multigene marker for lung predicting the prognosis of lung adenocarcinoma (LUAD) patients by bioinformatic analysis based on EMT-related genes. Gene sets associated with EMT were downloaded from the EMT-gene database, and RNA-seq of LUAD and clinical information of patients were downloaded from the TCGA database. Differentially expressed genes were screened by difference analysis. Survival analysis was performed to identify genes associated with LUAD prognosis, and overlapping genes were taken for all the three. Prognosis-related genes were further determined by combining LASSO regression analysis for establishing a prediction signature, and the risk score equation for the prognostic model was established using multifactorial COX regression analysis to construct a survival prognostic model. The model accuracy was evaluated using subject working characteristic curves. According to the median value of risk score, samples were divided into a high-risk group and low-risk group to observe the correlation with the clinicopathological characteristics of patients. Combined with the results of one-way COX regression analysis, HGF, PTX3, and S100P were considered as independent predictors of LUAD prognosis. In lung cancer tissues, HGF and PTX3 expression was downregulated and S100P expression was upregulated. Kaplan-Meier, COX regression analysis showed that HGF, PTX3, and S100P were prognostic independent predictors of LUAD, and high expressions of all the three were all significantly associated with immune cell infiltration. The present study provided potential prognostic predictive biological markers for LUAD patients, and confirmed EMT as a key mechanism in LUAD progression.

Genomic and molecular features distinguish young adult cancer from later-onset cancer.

Young adult cancer has increased in incidence worldwide, but its molecular etiologies remain unclear. We systematically characterize genomic profiles of young adult tumors with ages of onset ≤50 years and compare them to later-onset tumors using over 6,000 cases across 14 cancer types. While young adult tumors generally show lower mutation burdens and comparable copy-number variation rates compared to later-onset cases, they are enriched for multiple driver mutations and copy-number alterations in subtype-specific contexts. Characterization of tumor immune microenvironments reveals pan-cancer patterns of elevated TGF-ß response/dendritic cells and lower IFN-γ response/macrophages relative to later-onset tumors, corresponding to age-related responses to immunotherapy in several cancer types. Finally, we identify prevalent clinically actionable events that disproportionally affect young adult or later-onset cases. The resulting catalog of age-related molecular drivers can guide precision diagnostics and treatments for young adult cancer.

Comprehensive Bioinformatics Analysis to Identify the Gene HMMR Associated With Lung Adenocarcinoma Prognosis and Its Mechanism of Action in Multiple Cancers.

BACKGROUND: Lung cancer is the third most frequently diagnosed cancer in the world, with lung adenocarcinoma (LUAD) as the most common pathological type. But studies on the predictive effect of a single gene on LUAD are limited. We aimed to discover new predictive markers for LUAD. METHODS: Differentially high-expressed genes at each stage were obtained from the TCGA and GTEx databases. The functions of these genes were investigated through GO enrichment and KEGG pathway analyses. Then, the key genes were selected by applying whole gene overall survival time. The expression of the key gene was studied in LUAD, and survival analysis was performed using Kaplan-Meier mapper, followed by univariate and multifactorial COX analysis. Finally, the gene expression and its prognostic significance in the pan-cancer were examined. RESULTS: A total of 10,106 DEGs were obtained from the two datasets. The top 266 differentially upregulated genes intersected with the top 1,497 overall survival-related genes, and 87 key genes were identified. High-expressed HMMR was associated with a poor prognosis of LUAD. Univariate and multifactorial Cox analysis showed that HMMR was an independent prognostic factor for LUAD patients. A high HMMR expression was strongly associated with the overall survival (OS) and disease-specific survival (DSS) in 11 cancer types and with poorer OS, DSS, and PFI in 10 cancer types. CONCLUSION: HMMR may be an independent prognostic indicator and an important biomarker in diagnosing and predicting the survival of LUAD patients. Also, HMMR may be a key predictor of a variety of cancers.

Non-cancer-related pathogenic germline variants and expression consequences in ten-thousand cancer genomes.

BACKGROUND: DNA sequencing is increasingly incorporated into the routine care of cancer patients, many of whom also carry inherited, moderate/high-penetrance variants associated with other diseases. Yet, the prevalence and consequence of such variants remain unclear. METHODS: We analyzed the germline genomes of 10,389 adult cancer cases in the TCGA cohort, identifying pathogenic/likely pathogenic variants in autosomal-dominant genes, autosomal-recessive genes, and 59 medically actionable genes curated by the American College of Molecular Genetics (i.e., the ACMG 59 genes). We also analyzed variant- and gene-level expression consequences in carriers. RESULTS: The affected genes exhibited varying pan-ancestry and population-specific patterns, and overall, the European population showed the highest frequency of pathogenic/likely pathogenic variants. We further identified genes showing expression consequence supporting variant functionality, including altered gene expression, allelic specific expression, and mis-splicing determined by a massively parallel splicing assay. CONCLUSIONS: Our results demonstrate that expression-altering variants are found in a substantial fraction of cases and illustrate the yield of genomic risk assessments for a wide range of diseases across diverse populations.

Partial depletion and repopulation of microglia have different effects in the acute MPTP mouse model of Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive and selective degeneration of dopaminergic neurons. Microglial activation and neuroinflammation are associated with the pathogenesis of PD. However, the relationship between microglial activation and PD pathology remains to be explored. MATERIALS AND METHODS: An acute regimen of MPTP was administered to adult C57BL/6J mice with normal, much reduced or repopulated microglial population. Damages of the dopaminergic system were comprehensively assessed. Inflammation-related factors were assessed by quantitative PCR and Multiplex immunoassay. Behavioural tests were carried out to evaluate the motor deficits in MPTP-challenged mice. RESULTS: The receptor for colony-stimulating factor 1 inhibitor PLX3397 could effectively deplete microglia in the nigrostriatal pathway of mice via feeding a PLX3397-formulated diet for 21 days. Microglial depletion downregulated both pro-inflammatory and anti-inflammatory molecule expression at baseline and after MPTP administration. At 1d post-MPTP injection, dopaminergic neurons showed a significant reduction in PLX3397-fed mice, but not in control diet (CD)-fed mice. However, partial microglial depletion in mice exerted little effect on MPTP-induced dopaminergic injuries compared with CD mice at later time points. Interestingly, microglial repopulation brought about apparent resistance to MPTP intoxication. CONCLUSIONS: Microglia can inhibit PD development at a very early stage; partial microglial depletion has little effect in terms of the whole process of the disease; and microglial replenishment elicits neuroprotection in PD mice.

Mapping QTL for seedling morphological and physiological traits under normal and salt treatments in a RIL wheat population.

KEY MESSAGE: The genetic basis of 27 seedling traits under normal and salt treatments was fully analyzed in a RIL wheat population, and seven QTL intervals were validated in two other genetic populations. Soil salinity seriously constrains wheat (Triticum aestivum L.) production globally by influencing its growth and development. To explore the genetic basis of salt tolerance in wheat, a recombinant inbred line (RIL) population derived from a cross between high-yield wheat cultivar Zhongmai 175 (ZM175) and salt-tolerant cultivar Xiaoyan 60 (XY60) was used to map QTL for seedling traits under normal and salt treatments based on a high-density genetic linkage map. A total of 158 stable additive QTL for 27 morphological and physiological traits were identified and distributed on all wheat chromosomes except 3A and 4D. They explained 2.35-46.43% of the phenotypic variation with a LOD score range of 2.61-40.38. The alleles from XY60 increased corresponding traits for 100 QTL, while the alleles from ZM175 had positive effects for the other 58 QTL. Nearly half of the QTL (78/158) were mapped in nine QTL clusters on chromosomes 2A, 2B, 2D, 4B, 5A, 5B, 5D, and 7D (2), respectively. To prove the reliability and potentiality in molecular marker-assisted selection (MAS), seven QTL intervals were validated in two other genetic populations. Besides additive QTL, 94 pairs of loci were detected with significant epistatic effect and 20 QTL were found to interact with treatment. This study provides a full elucidation of the genetic basis of seedling traits (especially root system-related traits) associated with salt tolerance in wheat, and the developed kompetitive allele-specific PCR markers closely linked to stable QTL would supply strong supports to MAS in salt-tolerant wheat breeding.

[Inhibition of Microcystis aeruginosa by Bacillus subtilis fmb60 non-ribosome peptide metabolites].

Microcystis aeruginosa, a type of algal bloom microalgae, is widely distributed in water, causing serious deteriorated effects on humans and the ecological environment. As a biocontrol microorganism, Bacillus subtilis can synthesize various bioactive substances through non-ribosomal peptide synthetase, to inhibit the growth of M. aeruginosa. Thus, it is imperative to investigate the non-ribosomal peptide (NRP) metabolites of B. subtilis fmb60. Three NRP metabolites from B. subtilis fmb60 including bacillibactin, surfactin and fengycin were extracted and identified by genome mining technology. The growth inhibition of M. aeruginosa was studied by adding various concentrations of NRP metabolites. The half-effect concentration value (EC50.4 d) of M. aeruginosa was 26.5 mg/L after incubation for 4 days. With the increasing concentration, the inhibitory effects of NRP metabolites of B. subtilis fmb60 on M. aeruginosa was enhanced significantly. Compared with the control group, with the addition of 50 mg/L NRP metabolites to the M. aeruginosa, the content of Fv/Fm, Fv/Fo and Yield parameter after cultured for 4 days were decreased by 2.8%, 1.7% and 2.0%, respectively. Those findings indicate that the NRP metabolites of B. subtilis fmb60 can significantly inhibit the photosynthesis and metabolism of M. aeruginosa, which provides a theoretical foundation for the development of biological algae inhibitor of B. subtilis.

Are effect sizes in self-efficacy field changing over time? A meta-meta analysis.

Theories relating to self-efficacy have developed rapidly since Bandura first proposed the concept in 1977. In the past two decades, psychologists have carried out numerous studies to research the cultural and psychological changes in social development. The research topic of this study is whether self-efficacy changes over time. This study uses a meta-meta analysis and includes 13 meta-analyses, including 536 effect sizes, with a total sample size of 421,880. We find that individual self-efficacy increases over time, which may be related to social development trends. However, the effects of interventions on self-efficacy remain similar (Qmodel  = 1.807, df = 1, p > .05), and a possible explanation is that time effects of self-efficacy confuse the effects of intervention, because both in the intervention group and control group, the average of self-efficacy increases over time. And we find that a general decline in the predictive effects of self-efficacy (Qmodel  = 5.117, df = 1, p = .024), especially the ability to predict relatively objective variables (e.g. job performance, teaching effectiveness, and transfer of training). A possible explanation is that as social development people tend to overestimate their self-efficacy. Another possible explanation is that the effect sizes in the original studies being overrated, may due to intentional selective reporting or unintentional statistical errors.