Publications by authors named "Wenjie Luo"

40 Publications

Using artificial neural network in predicting the key fruit quality of loquat.

Food Sci Nutr 2021 Mar 29;9(3):1780-1791. Epub 2021 Jan 29.

College of Horticulture Nanjing Agricultural University Nanjing China.

The formation and regulation of loquat fruit quality have always been an important research field to improve fruit quality, commodities, and market value. Fruit size, soluble solids content, and titratable acid content represent the most important quality factors in loquat. Mineral nutrients in abundance or deficiency are among the most important key factor that affect fruit quality. In the present study, we use artificial neural network (ANN) to explore the effects of mineral nutrients in soil and leaves on the key fruit quality of loquat. The results show that the ANN model with the structure of 12-12-1 can predict the single fruit weight with the highest accuracy ( = .91), the ANN model with the structure of 10-11-1 can predict the soluble solid content with the highest accuracy ( = .91), and the ANN model with the structure of 9-10-1 can predict the titratable acid content with the highest accuracy ( = .95). Meanwhile, we also conduct sensitivity analysis to analyze the relative contribution of mineral nutrients in soils and leaves to determine of the key fruit quality. In terms of relative contribution, Ca, Fe, and Mg content in soils and Zn, K, and Ca content in leaves contribute relatively largely to a single fruit weight, Mn, Fe, and Mg content in soils and the N content in leaves contribute relatively largely to the soluble solid content, and the P, Ca, N, Mg, and Fe in leaves contribute relatively largely to the titratable acid content of loquat. The established artificial neural network prediction models can improve the quality of loquat fruit by optimizing the content of mineral elements in soils and leaves.
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http://dx.doi.org/10.1002/fsn3.2166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958548PMC
March 2021

A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain.

Nat Commun 2021 01 19;12(1):463. Epub 2021 Jan 19.

Brain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.

Splicing varies across brain regions, but the single-cell resolution of regional variation is unclear. We present a single-cell investigation of differential isoform expression (DIE) between brain regions using single-cell long-read sequencing in mouse hippocampus and prefrontal cortex in 45 cell types at postnatal day 7 ( www.isoformAtlas.com ). Isoform tests for DIE show better performance than exon tests. We detect hundreds of DIE events traceable to cell types, often corresponding to functionally distinct protein isoforms. Mostly, one cell type is responsible for brain-region specific DIE. However, for fewer genes, multiple cell types influence DIE. Thus, regional identity can, although rarely, override cell-type specificity. Cell types indigenous to one anatomic structure display distinctive DIE, e.g. the choroid plexus epithelium manifests distinct transcription-start-site usage. Spatial transcriptomics and long-read sequencing yield a spatially resolved splicing map. Our methods quantify isoform expression with cell-type and spatial resolution and it contributes to further our understanding of how the brain integrates molecular and cellular complexity.
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http://dx.doi.org/10.1038/s41467-020-20343-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815907PMC
January 2021

A Pentacyclic Triterpene from Targets γ-Secretase.

ACS Chem Neurosci 2020 09 3;11(18):2827-2835. Epub 2020 Sep 3.

Division of Life Science, State Key Laboratory of Molecular Neuroscience, and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay Road, Kowloon, Hong Kong, China.

Amyloid-beta peptides generated by β-secretase- and γ-secretase-mediated successive cleavage of amyloid precursor protein are believed to play a causative role in Alzheimer's disease. Thus, reducing amyloid-beta generation by modulating γ-secretase remains a promising approach for Alzheimer's disease therapeutic development. Here, we screened fruit extracts of Ait. (Oleaceae) and identified active fractions that increase the C-terminal fragment of amyloid precursor protein and reduce amyloid-beta production in a neuronal cell line. These fractions contain a mixture of two isomeric pentacyclic triterpene natural products, 3--- or 3----coumaroyl maslinic acid (OCMA), in different ratios. We further demonstrated that -OCMA specifically inhibits γ-secretase and decreases amyloid-beta levels without influencing cleavage of Notch. By using photoactivatable probes targeting the subsites residing in the γ-secretase active site, we demonstrated that -OCMA selectively affects the S1 subsite of the active site in this protease. Treatment of Alzheimer's disease transgenic model mice with -OCMA or an analogous carbamate derivative of a related pentacyclic triterpene natural product, oleanolic acid, rescued the impairment of synaptic plasticity. This work indicates that the naturally occurring compound -OCMA and its analogues could become a promising class of small molecules for Alzheimer's disease treatment.
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http://dx.doi.org/10.1021/acschemneuro.0c00389DOI Listing
September 2020

25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner.

J Neuroinflammation 2020 Jun 17;17(1):192. Epub 2020 Jun 17.

Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.

Background: Genome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Cholesterol 25-hydroxylase (CH25H), the enzyme responsible for 25-HC production, has also been found to be one of the disease-associated microglial (DAM) genes that are upregulated in the brain of AD and AD transgenic mouse models.

Methods: We used real-time PCR and immunoblotting to examine CH25H expression in human AD brain tissue and in transgenic mouse brain tissue-bearing amyloid-β plaques or tau pathology. The innate immune response of primary mouse microglia under different treatment conditions or bearing different genetic backgrounds was analyzed using ELISA, western blotting, or immunocytochemistry.

Results: We found that CH25H expression is upregulated in human AD brain tissue and in transgenic mouse brain tissue-bearing amyloid-β plaques or tau pathology. Treatment with the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) markedly upregulates CH25H expression in the mouse brain and stimulates CH25H expression and 25-HC secretion in mouse primary microglia. We found that LPS-induced microglial production of the pro-inflammatory cytokine IL-1β is markedly potentiated by 25-HC and attenuated by the deletion of CH25H. Microglia expressing apolipoprotein E4 (apoE4), a genetic risk factor for AD, produce greater amounts of 25-HC than apoE3-expressing microglia following treatment with LPS. Remarkably, 25-HC treatment results in a greater level of IL-1β secretion in LPS-activated apoE4-expressing microglia than in apoE2- or apoE3-expressing microglia. Blocking potassium efflux or inhibiting caspase-1 prevents 25-HC-potentiated IL-1β release in apoE4-expressing microglia, indicating the involvement of caspase-1 inflammasome activity.

Conclusion: 25-HC may function as a microglial-secreted inflammatory mediator in the brain, promoting IL-1β-mediated neuroinflammation in an apoE isoform-dependent manner (E4>E2/E3) and thus may be an important mediator of neuroinflammation in AD.
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http://dx.doi.org/10.1186/s12974-020-01869-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298825PMC
June 2020

Injectable Therapeutic Organoids Using Sacrificial Hydrogels.

iScience 2020 May 12;23(5):101052. Epub 2020 Apr 12.

Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA. Electronic address:

Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method-by making use of the dynamic nature of hydrogels-could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.
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http://dx.doi.org/10.1016/j.isci.2020.101052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191221PMC
May 2020

Fish c-Jun N-Terminal Kinase (JNK) Pathway Is Involved in Bacterial MDP-Induced Intestinal Inflammation.

Front Immunol 2020 30;11:459. Epub 2020 Mar 30.

Hunan Provincial Key Laboratory of Nutrition and Quality Control of Aquatic Animals, Department of Biological and Environmental Engineering, Changsha University, Changsha, China.

The c-Jun NH-terminal kinases (JNKs) are an evolutionarily conserved family of serine/threonine protein kinases that play critical roles in the pathological process in species ranging from insects to mammals. However, the function of JNKs in bacteria-induced intestinal inflammation is still poorly understood. In this study, a fish JNK (JNK) pathway was identified, and its potential roles in bacterial muramyl dipeptide (MDP)-induced intestinal inflammation were investigated in . The present JNK was found to possess a conserved dual phosphorylation motif (TPY) in a serine/threonine protein kinase (S_TKc) domain and to contain several potential immune-related transcription factor binding sites, including nuclear factor kappa B (NF-κB), activating protein 1 (AP-1), and signal transducer and activator of downstream transcription 3 (STAT3), in its 5' flanking regions. Quantitative real-time PCR results revealed that the mRNA levels of the JNK pathway genes in the intestine were significantly upregulated after challenge with a bacterial pathogen () and MDP in a time-dependent manner. Additionally, the JNK pathway was found to be involved in regulating the MDP-induced expression levels of inflammatory cytokines (IL-6, IL-8, and TNF-α) in the intestine of grass carp. Moreover, the nutritional dipeptide carnosine and Ala-Gln could effectively alleviate MDP-induced intestinal inflammation by regulating the intestinal expression of JNK pathway genes and inflammatory cytokines in grass carp. Finally, fluorescence microscopy and dual-reporter assays indicated that JNK could associate with MKK4 and MKK7 involved in the regulation of the AP-1 signaling pathway. Overall, these results provide the first experimental demonstration that the JNK signaling pathway is involved in the intestinal immune response to MDP challenge in , which may provide new insight into the pathogenesis of inflammatory bowel disease.
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http://dx.doi.org/10.3389/fimmu.2020.00459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134542PMC
March 2021

MicroRNA-4317 predicts the prognosis of breast cancer and inhibits tumor cell proliferation, migration, and invasion.

Clin Exp Med 2020 Aug 11;20(3):417-425. Epub 2020 Apr 11.

Department of Thyroid and Breast Surgery, Shanghai First People's Hospital Baoshan Branch, No. 101, North Tongtai Road, Shanghai, 200940, China.

Previous researches have indicated that miR-4317 was aberrantly expressed in several tumors. However, the potential role of miR-4317 in breast cancer is still unclear. The aim of this study was to investigate the potential role of miR-4317 in breast cancer. The relative expression levels of miR-4317 were detected in breast cancer tissues and cell lines using qRT-PCR analysis. The Kaplan-Meier survival curve and multivariate Cox regression analyses were used to investigate the prognostic significance of miR-4317 in breast cancer. CCK-8 and Transwell assays were performed to evaluate the effects of miR-4317 on cell proliferation, migration, and invasion. The results showed that miR-4317 expression was decreased in breast cancer tissues and cell lines. Downregulation of miR-4317 was significantly associated with lymph node metastasis, TNM stage, and poor prognosis. Overexpression of miR-4317 inhibited proliferation, migration, and invasion of breast cancer cells, while downregulation of miR-4317 exhibited the opposite effects. MYD88 may be a direct target of miR-4317. The results suggest miR-4317 may play a tumor suppressor role in breast cancer and inhibit proliferation, migration, and invasion of breast cancer cells by targeting MYD88. The findings provide novel evidence of miR-4317 as a potential prognostic biomarker and therapeutic target for breast cancer.
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http://dx.doi.org/10.1007/s10238-020-00625-4DOI Listing
August 2020

RuP nanoparticles on ordered macroporous hollow nitrogen-doped carbon spheres for efficient hydrogen evolution reaction.

Nanotechnology 2020 May 23;31(29):295401. Epub 2020 Mar 23.

Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.

The design of highly active, Earth-abundant and stable electrocatalysts is important for efficient water splitting. In this work, we report the fabrication of RuP and RuP nanoparticles supported on ordered macroporous N-doped carbon hollow spheres (RuP/H-NC and RuP/H-NC) through a facile and scalable space-confined pyrolysis process. The RuP/H-NC catalyst exhibits Pt-like activity in alkaline electrolyte, by means of the macroporous structure with a larger specific area and more exposed active sites, as well as the synergistic effect between the RuP nanoparticles and N-doped carbon. Specifically, the RuP/H-NC catalyst yields superior hydrogen evolution reaction activity in terms of low overpotential of 19 mV in 1 M KOH to achieve a current density of 10 mA cm and excellent durability, outperforming RuP/H-NC and most of the reported non-Pt catalysts. Further density function theory calculation reveals that RuP is more intrinsically active with favorable hydrogen adsorption Gibbs free energy than that of RuP.
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http://dx.doi.org/10.1088/1361-6528/ab824bDOI Listing
May 2020

Association between blooming time and climatic adaptation in .

Ecol Evol 2020 Jan 20;10(1):292-306. Epub 2019 Dec 20.

Nanjing Agricultural University Nanjing China.

Sieb. et Zucc. is an important fruit crop of the subtropical region, originating in China. It blooms earlier than other deciduous fruit trees, but different regions have different blooming periods. The time of anthesis is related to the dormancy period, and a certain amount of chilling promotes bud break and blooming. To identify the relationship between blooming time and the climatic adaptation of cultivars in China, the nuclear and chloroplast genomes of 19 cultivars from the main cultivation areas of in China were resequenced. The average depth of coverage was 34X-76X, and a total of 388,134 single nucleotide polymorphisms were located within the coding regions of the gene (CDs). Additionally, the 19 cultivar accessions were divided into three groups based on their blooming time: early, mid, and late. Associated with the blooming time groups, 21 selective sweep regions were identified, which could provide evidence supporting the possible model of domestication originating due to natural selection. Furthermore, we identified a flowering gene, (), seems to affect the blooming time and the climatic adaptation of cultivars. This study is a major step toward understanding the climatic adaptation of cultivars in China.
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http://dx.doi.org/10.1002/ece3.5894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972806PMC
January 2020

The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction.

Nat Commun 2020 01 16;11(1):319. Epub 2020 Jan 16.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.
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http://dx.doi.org/10.1038/s41467-019-14082-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965647PMC
January 2020

HLMethy: a machine learning-based model to identify the hidden labels of mA candidates.

Plant Mol Biol 2019 Dec 13;101(6):575-584. Epub 2019 Nov 13.

College of Water Resources and Architectural Engineering, Northwest A & F University, Yangling, 712100, Shaanxi, China.

Key Message: We developed a machine learning-based model to identify the hidden labels of mA candidates from noisy m6A-seq data. Peak-calling approaches, such as MeRIP-seq or mA-seq, are commonly used to map mA modifications. However, these technologies can only map mA sites with 100-200 nt resolution and cannot reveal the precise location or the number of modified residues in a transcript. To address this challenge, we developed a novel machine learning-based approach, named HLMethy, to assign labels to mA candidates from noisy mA-seq data. The multiple instance learning framework was adopted and two different training strategies were used to generate the classification model. To test the performance of our model, the mA sites with single-base resolution were used and our model achieved comparable performance against existing instance-level predictors, which suggest that our model has the potential to improve the data quality of mA-seq at reduced costs. What's more, our generic framework can be extended to other newly found modifications that are found by peak-calling approaches. The source code of HLMethy is available at https://github.com/liuze-nwafu/HLMethy.
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http://dx.doi.org/10.1007/s11103-019-00930-xDOI Listing
December 2019

Comparative analysis of the complete chloroplast genome among , . , and . .

Hortic Res 2019 21;6:89. Epub 2019 Jul 21.

1College of Horticulture, Nanjing Agricultural University, 210095 Nanjing, China.

Sieb. et Zucc., . L., and . L. are economically important fruit trees in temperate regions. These species are taxonomically perplexing because of shared interspecific morphological traits and variation, which are mainly attributed to hybridization. The chloroplast is cytoplasmically inherited and often used for evolutionary studies. We sequenced the complete chloroplast genomes of , and using Illumina sequencing followed by de novo assembly. The three chloroplast genomes exhibit a typical quadripartite structure with conserved genome arrangement, structure, and moderate divergence. The lengths of the genomes are 157,815, 157,797, and 157,916 bp, respectively. The length of the large single-copy region (LSC) region is 86,113, 86,283, and 86,122 bp, and the length of the SSC region is 18,916, 18,734, and 19,028 bp; the IR region is 26,393, 26,390, and 26,383 bp, respectively. Each of the three chloroplast genomes encodes 133 genes, including 94 protein-coding, 31 tRNA, and eight rRNA genes. Differential gene analysis for the three species revealed that is a unique gene in ; in contrast, the gene is only present in and , though the position of the gene in these chloroplast genomes differs. Further comparative analysis of the complete chloroplast genome sequences revealed that the ORF genes and the sequences of linked regions and , and , and , and , and and are significantly different and may be used as molecular markers in taxonomic studies. Phylogenetic evolution analysis of the three species suggests that has a closer genetic relationship to than to .
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http://dx.doi.org/10.1038/s41438-019-0171-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804877PMC
July 2019

HIV incidence and cohort retention among men who have sex with men in Hangzhou, China: A prospective cohort study.

Medicine (Baltimore) 2019 Oct;98(40):e17419

Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut.

Prospective cohort studies have been conducted to estimate HIV incidence among men who have sex with men (MSM) in first-line megacities cities (>10 million residents) in China, but few in the second-line large- or middle-size cities. This study was to investigate HIV incidence and cohort retention among MSM in a second-line city Hangzhou in eastern China.A total of 523 HIV-seronegative MSM were recruited during September 2014 to September 2015, and were followed up prospectively at 3, 6, 9, and 12 months. Questionnaire interviews were conducted, and laboratory tests were performed to evaluate baseline syphilis infection and HIV seroconversions. Chi-square test and logistic regression model were used to identify factors associated with cohort retention rate and syphilis prevalence.Of 523 participants, 137 (26.2%) completed 6-month follow-up, and use of Internet for recruiting study participants (vs other recruitments: adjusted odds ratio [AOR] = 0.5; 95% confidence interval [CI]: 0.3-0.8) and being homosexual (vs heterosexual or bisexual: AOR = 0.6; 95% CI: 0.4-0.9) were associated with lower cohort retention. The overall HIV incidence during 12 months of follow-up was 6.6 per 100 person-years (95% CI: 3.4-9.8/100 PY). The prevalence of syphilis at baseline was 6.5% (95% CI: 4.4%-8.6%), and disclosing sexual orientation (AOR = 0.4, 95% CI: 0.2-0.9) was associated with lower risk of syphilis infection.HIV is spreading rapidly among MSM in the second-line Chinese city. Effective interventions are needed to target this population in both first-line megacities and second-line large and middle-size cities.
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http://dx.doi.org/10.1097/MD.0000000000017419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783165PMC
October 2019

High-throughput sequencing analysis of microbial community diversity in response to indica and japonica bar-transgenic rice paddy soils.

PLoS One 2019 9;14(9):e0222191. Epub 2019 Sep 9.

Hainan Key Laboratory for Sustainable Utilization of Tropical Bio-resources, Institute of Tropical Agriculture and Forestry, Hainan University, Haikou, China.

Potential environmental risks of genetically modified (GM) crops have raised concerns. To better understand the effect of transgenic rice on the bacterial community in paddy soil, a field experiment was carried out using pairs of rice varieties from two subspecies (indica and japonica) containing bar transgene with herbicide resistance and their parental conventional rice. The 16S rRNA gene of soil genomic DNA from different soil layers at the maturity stage was sequenced using high-throughput sequencing on the Illumina MiSeq platform to explore the microbial community diversity among different rice soils. There were no significant differences in diversity indices between transgenic japonica rice and its sister conventional rice (japonica pair) among different soil layers, but, significant differences was observed between transgenic indica rice and its conventional rice (indica pair) in the topsoil layer around concentrated rice roots according to the ace diversity index. Though the japonica rice soil and indica rice soil were shared several key genera, including Rivibacter, Anaeromyxobacter, Roseomonas, Geobacter, Thiobacillus, Clostridium, and Desulfobulbus, the primary bacterial genera in indica rice soil were different from those in japonica rice. Synechococcus and Dechloromonas were present in japonica rice samples, while Chloronema, Flexibacter, and Blastocatella were observed in indica rice soil. Moreover, the abundance of genera between GM and non-GM varieties in japonica rice was significantly different from indica rice, and several bacterial communities influenced these differences. Anaerovorax was more abundant in transgenic japonica rice soil than conventional rice soil, while it was deficient in transgenic indica rice soil compared to conventional rice soil, and opposite responses to Deferrisoma were in that of indica rice. Thus, we concluded that transgenic indica and japonica rice had different effects on soil bacteria compared with their corresponding sister conventional rice. However, these composition and abundance difference only occurred for a few genera but had no effect on the primary genera and soil characteristics were mainly contributed to these differences. Thus, differences in bacterial community structure can be ignored when evaluating the impacts of transgenic rice in the complex soil microenvironment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733487PMC
March 2020

Facile Synthesis of Monodispersed SiO@FeO Core-Shell Colloids for Printing and Three-Dimensional Coating with Noniridescent Structural Colors.

ACS Omega 2019 Jan 8;4(1):528-534. Epub 2019 Jan 8.

School of Materials and Energy, Guangdong University of Technology, Guangzhou 510006, P. R. China.

Amorphous photonic structures (APSs) with short-range ordered arrangement have attracted great interest because of their wide view angles. However, the presented methods for the APSs color printing and 3D coating on different substrates and curvatures are lack of control. Here, APSs with angle-independent structural colors were fabricated by the self-assembly of SiO@FeO core-shell nanostructures, which were prepared by the hydrolysis of Fe(acac) on the silica surfaces. The size of SiO@FeO core-shell colloids can be controlled well through the tuning of SiO particle size, whereas the coverage of FeO on silica surfaces can be precisely tailored through altering the mass ratio between FeO precursor and SiO. APSs with only short-range ordered structures, uniform noniridescent structural colors, and high color visibility can be obtained through the self-assembly of SiO@FeO colloids of different particle sizes in a few minutes. They are mainly attributed to the weak electrostatic repulsion interactions between SiO@FeO colloids because of the partial coverage of FeO on silica surfaces and absorption of the incoherent multiple scattering of visible light from FeO. Moreover, SiO@FeO colloids show good adhesion to various substrates, such as paper, glass, plastics, resins, ceramics, and wood, which facilitates the formation of uniform APSs on different substrates. Multicolor prints and 3D coating of APSs on substrates with different curves and roughness can be realized on the basis of the fast assembly of SiO@FeO colloids.
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http://dx.doi.org/10.1021/acsomega.8b02987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648414PMC
January 2019

Molecular characterization and taurine regulation of two novel CDOs (CDO1 and CDO2) from Carassius auratus.

Comp Biochem Physiol B Biochem Mol Biol 2019 Sep 6;235:54-61. Epub 2019 Jun 6.

State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Normal University, Changsha 410081, China; Hunan Provincial Key Laboratory of Nutrition and Quality Control of Aquatic Animals, Department of Biological and Environmental Engineering, Changsha University, Changsha 410022, China. Electronic address:

Cysteine oxygenase (CDO) is a mononuclear nonhemoglobin enzyme that catalyzes the production of taurine through the cysteine (Cys) pathway and plays a key role in the biosynthesis of taurine in mammals. However, the function of CDOs in bony fish remains poorly understood. In this study, we cloned CDO genes (CaCDO1 and CaCDO2) from Carassius auratus. The cDNA sequences of both CaCDO1 and CaCDO2 encoded putative proteins with 201 amino acids, which included structural features typical of the CDO protein family. Multiple sequence alignment and phylogenetic analysis showed that CaCDO1 and CaCDO2 shared high sequence identities and similarities with C. carpio homologs. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that CaCDO1 and CaCDO2 were both broadly expressed in all selected tissues and developmental stages in C. auratus but had differing mRNA levels. In addition, compared to those of the taurine-free group, the in vivo mRNA expression levels of both CaCDO1 and CaCDO2 significantly decreased with increasing dietary taurine levels from 1.0 to 9.0 g/kg. Furthermore, in vitro taurine treatments showed similar inhibitory effects on the expression of CaCDO1 and CaCDO2 in the intestines of C. auratus. Our results also showed that the mRNA expression of CaCDO2 in the intestines was higher than that of CaCDO1 in response to in vivo and in vitro taurine supplementation. Overall, these data may provide new insights into the regulation of fish CDO expression and provide valuable knowledge for improving dietary formulas in aquaculture.
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http://dx.doi.org/10.1016/j.cbpb.2019.06.001DOI Listing
September 2019

The complexity of tau in Alzheimer's disease.

Neurosci Lett 2019 07 25;705:183-194. Epub 2019 Apr 25.

Helen and Robert Appel Alzheimer's Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, USA. Electronic address:

Alzheimer's disease (AD) is characterized by two major pathological lesions in the brain, amyloid plaques and neurofibrillary tangles (NFTs) composed mainly of amyloid-β (Aβ) peptides and hyperphosphorylated tau, respectively. Although accumulation of toxic Aβ species in the brain has been proposed as one of the important early events in AD, continued lack of success of clinical trials based on Aβ-targeting drugs has triggered the field to seek out alternative disease mechanisms and related therapeutic strategies. One of the new approaches is to uncover novel roles of pathological tau during disease progression. This review will primarily focus on recent advances in understanding the contributions of tau to AD.
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http://dx.doi.org/10.1016/j.neulet.2019.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060758PMC
July 2019

Mitogen-activated protein kinase kinase 6 is involved in the immune response to bacterial di-/tripeptide challenge in grass carp Ctenopharyngodon idella.

Fish Shellfish Immunol 2019 Jan 28;84:795-801. Epub 2018 Oct 28.

Hunan Provincial Key Laboratory of Nutrition and Quality Control of Aquatic Animals, Department of Biological and Environmental Engineering, Changsha University, Changsha, 410022, China; State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Normal University, Changsha, 410081, China. Electronic address:

Mitogen-activated protein kinase kinase 6 (MKK6) is an essential component of the p38MAPK signaling pathway, which is involved in the modulation of inflammation, cell apoptosis and survival responses in mammals. However, the function of MKK6s in teleosts is still unclear. In this study, a fish MKK6 homolog (CiMKK6) was first identified from the grass carp (Ctenopharyngodon idella), a freshwater fish. CiMKK6 cDNA encodes a putative protein of 357 amino acids that contains conserved structural characteristics of the MKK6 family, including the S_TKc domain, SVAKT motif and DVD site. The deduced CiMKK6 protein exhibits high sequence homology with other reported fish MKK6s and shares the closest relationship with MKK6 from Danio rerio. Quantitative real-time PCR (qRT-PCR) analysis revealed that CiMKK6 mRNA was widely expressed in all tested tissues and stages of embryonic development. Additionally, the transcript levels of CiMKK6 in the intestine were significantly upregulated in response to bacterial muramyl dipeptide (MDP) and L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP) stimulation. Moreover, subcellular localization analysis indicated that CiMKK6 was distributed in both the cytoplasm and the nucleus of HEK293T cells. Finally, overexpression of CiMKK6 significantly enhanced the transcriptional activity of the AP-1 reporter gene in HEK293T cells. Overall, these findings may help better clarify the immune function of teleost MKK6s and provide new insight into the immune defense mechanisms of grass carp.
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http://dx.doi.org/10.1016/j.fsi.2018.10.073DOI Listing
January 2019

Single-cell isoform RNA sequencing characterizes isoforms in thousands of cerebellar cells.

Nat Biotechnol 2018 Oct 15. Epub 2018 Oct 15.

Brain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, New York, USA.

Full-length RNA sequencing (RNA-Seq) has been applied to bulk tissue, cell lines and sorted cells to characterize transcriptomes, but applying this technology to single cells has proven to be difficult, with less than ten single-cell transcriptomes having been analyzed thus far. Although single splicing events have been described for ≤200 single cells with statistical confidence, full-length mRNA analyses for hundreds of cells have not been reported. Single-cell short-read 3' sequencing enables the identification of cellular subtypes, but full-length mRNA isoforms for these cell types cannot be profiled. We developed a method that starts with bulk tissue and identifies single-cell types and their full-length RNA isoforms without fluorescence-activated cell sorting. Using single-cell isoform RNA-Seq (ScISOr-Seq), we identified RNA isoforms in neurons, astrocytes, microglia, and cell subtypes such as Purkinje and Granule cells, and cell-type-specific combination patterns of distant splice sites. We used ScISOr-Seq to improve genome annotation in mouse Gencode version 10 by determining the cell-type-specific expression of 18,173 known and 16,872 novel isoforms.
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http://dx.doi.org/10.1038/nbt.4259DOI Listing
October 2018

A guanidine-appended scyllo-inositol derivative AAD-66 enhances brain delivery and ameliorates Alzheimer's phenotypes.

Sci Rep 2017 10 26;7(1):14125. Epub 2017 Oct 26.

Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.

Alzheimer's disease (AD) is a degenerative brain disease that destroys memory and other important mental functions but lacks efficient therapeutic agents. Blocking toxic amyloid β (Aβ) could be beneficial for AD and represents a promising therapeutic strategy for AD treatment. scyllo-Inositol (SI) is a potential therapeutic for AD by directly interacting with the Aβ peptide to inhibit Aβ42 fiber formation. Clinical studies of SI showed promising benefits on mild to moderate AD, however, with limitations on dosage regime. A new strategy to enhance the brain delivery of SI is needed to achieve the efficacy with minimum adverse effects. Herein, we report that a novel guanidine-appended SI derivative AAD-66 resulted in more effective reductions of brain Aβ and plaque deposits, gliosis, and behavioral memory deficits in the disease-established 5xFAD mice. Overall, our present study reveals the potential of AAD-66 as a promising therapeutic agent for AD.
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http://dx.doi.org/10.1038/s41598-017-14559-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658413PMC
October 2017

ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy.

Nature 2017 09 20;549(7673):523-527. Epub 2017 Sep 20.

Memory and Aging Center, Department of Neurology, University of California, San Francisco, California 94143 USA.

APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-α (TNF-α) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-α. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an ε4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-β pathology with symptomatic Alzheimer disease who usually have tau pathology, ε4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau pathogenesis, neuroinflammation, and tau-mediated neurodegeneration independently of amyloid-β pathology. ApoE4 exerts a 'toxic' gain of function whereas the absence of ApoE is protective.
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http://dx.doi.org/10.1038/nature24016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641217PMC
September 2017

ApoE4-associated phospholipid dysregulation contributes to development of Tau hyper-phosphorylation after traumatic brain injury.

Sci Rep 2017 09 12;7(1):11372. Epub 2017 Sep 12.

James J. Peters VA Medical Center, Neurology Service, Bronx, NY, 10468, USA.

The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP levels in ApoE4 mice did not increase after blast TBI. Following blast TBI, phospho-Tau (pTau) levels were unchanged in ApoE3 mice, whereas in ApoE4 mice, levels of pTau were significantly increased. To determine the causal relationship between changes in pTau and PIP/synj1 levels after TBI, we tested if down-regulation of synj1 prevented blast-induced Tau hyper-phosphorylation. Knockdown of synj1 decreased pTau levels in vitro, and abolished blast-induced elevation of pTau in vivo. Blast TBI increased glycogen synthase kinase (GSK)-3β activities in ApoE4 mice, and synj1 knockdown inhibited GSK3β phosphorylation of Tau. Together, these data suggest that ApoE proteins regulate brain phospholipid homeostasis in response to TBI and that the ApoE4 isoform is dysfunctional in this process. Down-regulation of synj1 rescues blast-induced phospholipid dysregulation and prevents development of Tau hyper-phosphorylation in ApoE4 carriers.
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http://dx.doi.org/10.1038/s41598-017-11654-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595858PMC
September 2017

Molecular cloning and characterization of antimicrobial peptides from skin of Hylarana guentheri.

Acta Biochim Biophys Sin (Shanghai) 2017 May;49(5):450-457

Key Laboratory of Tropical Biological Resources, Ministry of Education, College of Marine Science, Hainan University, Haikou 570228, China.

The cDNAs encoding antimicrobial peptides (AMPs) in the skin of Hylarana guentheri were identified, namely temporin (five peptides, termed temporin-GHa-GHd and temporin-GUa), brevinin-1 (one peptide, brevinin-1GUb), and brevinin-2 (eight peptides, brevinin-2GHd-2GHj, and brevinin-2GHb). Eleven of the 14 peptides have novel primary structures. Synthesized temporin GHa-GHd have broad-spectrum antimicrobial activities against Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Escherichia coli, Vibrio alginolyticus, and Pseudomonas aeruginosa), as well as fungus (Candida albicans). Among these tested strains, S. aureus was the most sensitive to temporin-GHa-GHd with minimum inhibitory concentration (MIC) values between 6.8 and 12.9 μM. They also exhibited antimicrobial activities against Methicillin-resistant S. aureus with the MIC ranging from 12.7 to 51.7 μM. Interestingly, secondary structure prediction shows that there is no α-helix in temporin-GHb, which illustrates that α-helix is not required for the antimicrobial activity of temporin-GHb. NaCl (at final concentrations of 0.15-2 M) decreased the antimicrobial activity of temporin-GHa-GHd slightly, while human serum and S. aureus V8 proteinase had no effect on the antimicrobial activity. Scanning electron microscopy images of E. coli and S. aureus showed that the surface of microbial cells was considerably rough and shrived after 1 h of treatment with temporin-GHa-GHd at 37°C. The stabilities of temporin-GHa-GHd in human serum or in S. aureus V8 proteinase make them to be promising candidates of novel antimicrobial agents or models for the development of novel AMPs.
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http://dx.doi.org/10.1093/abbs/gmx023DOI Listing
May 2017

TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy.

Neuron 2016 05;90(4):724-39

Department of Neurology, Yale University, New Haven, CT 06511, USA; Department of Neuroscience, Yale University, New Haven, CT 06511, USA. Electronic address:

Haplodeficiency of the microglia gene TREM2 increases risk for late-onset Alzheimer's disease (AD) but the mechanisms remain uncertain. To investigate this, we used high-resolution confocal and super-resolution (STORM) microscopy in AD-like mice and human AD tissue. We found that microglia processes, rich in TREM2, tightly surround early amyloid fibrils and plaques promoting their compaction and insulation. In Trem2- or DAP12-haplodeficient mice and in humans with R47H TREM2 mutations, microglia had a markedly reduced ability to envelop amyloid deposits. This led to an increase in less compact plaques with longer and branched amyloid fibrils resulting in greater surface exposure to adjacent neurites. This was associated with more severe neuritic tau hyperphosphorylation and axonal dystrophy around amyloid deposits. Thus, TREM2 deficiency may disrupt the formation of a neuroprotective microglia barrier that regulates amyloid compaction and insulation. Pharmacological modulation of this barrier could be a novel therapeutic strategy for AD.
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http://dx.doi.org/10.1016/j.neuron.2016.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898967PMC
May 2016

δ-COP modulates Aβ peptide formation via retrograde trafficking of APP.

Proc Natl Acad Sci U S A 2016 May 25;113(19):5412-7. Epub 2016 Apr 25.

Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065

The components involved in cellular trafficking and protein recycling machinery that have been associated with increased Alzheimer's disease (AD) risk belong to the late secretory compartments for the most part. Here, we hypothesize that these late unavoidable events might be the consequence of earlier complications occurring while amyloid precursor protein (APP) is trafficking through the early secretory pathway. We investigated the relevance to AD of coat protein complex I (COPI)-dependent trafficking, an early step in Golgi-to-endoplasmic reticulum (ER) retrograde transport and one of the very first trafficking steps. Using a complex set of imaging technologies, including inverse fluorescence recovery after photobleaching (iFRAP) and photoactivatable probes, coupled to biochemical experiments, we show that COPI subunit δ (δ-COP) affects the biology of APP, including its subcellular localization and cell surface expression, its trafficking, and its metabolism. These findings demonstrate the crucial role of δ-COP in APP metabolism and, consequently, the generation of amyloid-β (Aβ) peptide, providing previously nondescribed mechanistic explanations of the underlying events.
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http://dx.doi.org/10.1073/pnas.1604156113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868462PMC
May 2016

Tunable emission, energy transfer and charge compensation in Sr3(VO4)2:Sm(3+),P(5+),Na(+) phosphor.

Spectrochim Acta A Mol Biomol Spectrosc 2015 Nov 6;150:465-9. Epub 2015 Jun 6.

College of Mechanical Manufacture and Automation, Jinggangshan University, Ji'an 343009, China.

A series of Sr3(VO4)2:Sm(3+),P(5+),Na(+) phosphors are synthesized by using solid-state reaction method in air. The strongest emission band peaking at ∼600 nm is assigned to the (4)G5/2→(6)H7/2 transition of Sm(3+) ion, and the strong excitation peak at ∼402 nm due to (6)H5/2→(4)F7/2 transition indicates that these phosphors can be excited by near ultraviolet light emitting diode chip. Energy transfer (ET) between VO4(3-) group and Sm(3+) ion can be observed. Sr3(VO4)2:Sm(3+) phosphor with excitation 320 nm exhibits a systematically varied hues from green to yellow by changing Sm(3+) ion concentration from 0 to 6 mol%. The luminous mechanism of Sr3(VO4)2:Sm(3+) phosphor is explained by using the energy level diagrams of VO4(3-) group and Sm(3+) ion. The luminescence properties of Sr3(VO4)2:Sm(3+) phosphor can be improved and tuned by codoping the P(5+) and Na(+) ions due to ET and charge compensation. Lifetimes of Sr2.925Sm0.05(VO4)2, Sr2.925Sm0.05(V0.9P0.1O4)2, and Sr2.9Na0.05Sm0.05(V0.9P0.1O4)2 phosphors are 1.208, 1.219, and 0.796 ms, respectively. The experiment results are helpful to adjust the luminescence properties of Sm(3+)-doped other phosphors.
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http://dx.doi.org/10.1016/j.saa.2015.06.001DOI Listing
November 2015

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody.

Sci Rep 2015 Jun 9;5:11161. Epub 2015 Jun 9.

Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medical College of Cornell University, 413 East 69th Street, New York, NY10021.

Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer's disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies.
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http://dx.doi.org/10.1038/srep11161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460904PMC
June 2015

Effects of dexmedetomidine on cellular immunity of perioperative period in children with brain neoplasms.

Int J Clin Exp Med 2015 15;8(2):2748-53. Epub 2015 Feb 15.

Department of Anesthesiology, Putuo District People's Hospital Shanghai 200060, China.

Objective: To study the effects of dexmedetomidine (Dex) on cellular immunity during the perioperative period in children with brain neoplasms.

Methods: Forty children with brain neoplasms scheduled for selective operation were recruited and divided randomly into two groups. The Dex group was given a loading dose of 1 μg*kg(-1) Dex 15 minutes before anesthesia induction followed by a continuous infusion of 0.5 μg × kg(-1) × h(-1) Dex. Patients in control group received a same volume of normal saline for a same time period. Venous blood was collected before anesthesia (T0), 1 h after operation started (T1), immediately after operation ended (T2), 1 day after operation (T3) and 3 days after operation (T4), respectively.

Results: CD3 (+), CD4 (+), CD4 (+)/CD8 (+), NK and B cells at T1-T3 decreased significantly (P < 0.05) in both groups compared with those at T0, while the decrease of CD3 (+), CD4 (+), CD4 (+)/CD8 (+) and NK cells at T1-T3 and B cells at T1-T2 in Dex group was significantly less than the control group (P < 0.05). All values at T4 recovered to the level before anesthesia in both groups.

Conclusion: Dex given by a continuous intravenous infusion during general anesthesia may effectively inhibit the stress responses and reduce the inhibition of cellular immunity in children with brain neoplasms during the perioperative period.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402876PMC
May 2015

Hypertension enhances Aβ-induced neurovascular dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP.

J Cereb Blood Flow Metab 2016 Jan;36(1):241-52

Hypertension (HTN) doubles the risk of Alzheimer’s disease (AD), but the mechanisms remain unclear. Amyloid-β (Aβ), a key pathogenic factor in AD, induces cerebrovascular dysfunction. We hypothesized that HTN acts in concert with Aβ to amplify its deleterious cerebrovascular effects and to increase Aβ production. Infusion of angiotensin II (ANGII; intravenously) elevated blood pressure and attenuated the cerebral blood flow (CBF) response to whisker stimulation or the endothelium-dependent vasodilator acetylcholine (ACh) (P < 0.05). Neocortical application of Aβ in mice receiving ANGII worsened the responses to ACh (P < 0.05). The cerebrovascular dysfunction observed in Tg2576 mice, in which Aβ is elevated both in blood and in brain due to expression of mutated amyloid precursor protein (APP), was not aggravated by neocortical application of ANGII or by a 2-week administration of ‘slow pressor’ of ANGII (600 ng/kg per minute; subcutaneously). In contrast, ANGII aggravated the dysfunction in TgSwDI mice, in which Aβ is increased only in brain. Slow-pressor ANGII induced microvascular amyloid deposition in Tg2576 mice and enhanced β-secretase APP cleavage. In Chinese hamster ovary (CHO) cells producing Aβ, ANGII increased β-secretase activity, Aβ1-42, and the Aβ42/40 ratio. We conclude that HTN enhances amyloidogenic APP processing, effects that may contribute to the pathogenic interaction between HTN and AD.
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http://dx.doi.org/10.1038/jcbfm.2015.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758560PMC
January 2016