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1.
J Affect Disord ; 260: 91-96, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493645

RESUMO

BACKGROUND: Major depressive disorder (MDD) patients with comorbid anxiety symptoms showed obvious cognitive deficits. However, it remains unclear whether comorbid anxiety symptoms will make a specific contribution to cognitive deficits in MDD. METHODS: Executive function, processing speed, attention and memory were assessed in 162 MDD patients, and 142 healthy controls (HCs) by a comprehensive neuropsychological battery. 14-item Hamilton Anxiety Rating Scale (HAM-A) was used for anxiety symptoms and MDD patients with HAM-A total score >14 were classified into MDD with comorbid anxiety (MDDA) group. A multivariate analysis of covariance and regression models was conducted to evaluate the effects of anxiety symptoms on cognitive deficits. RESULTS: There were no significantly differences in all 4 cognitive domains between MDD alone and MDDA patients (all p < 0.05). In MDDA subgroup, HAM-A total score contributed to executive function and memory (both p < 0.05), while HAM-A psychic symptoms contributed to all 4 domains (all p < 0.05). Moreover, after controlling for the severity of depression, either anxiety symptoms shown as HAMA total score or psychic anxiety symptoms only contributed significantly to the executive function performance. LIMITATIONS: The cross-sectional design made it hard to acquire a cognitive performance trajectory accompanied by the fluctuations in anxiety symptoms. CONCLUSION: Our findings suggest that there is no significant difference in cognitive performance between MDD alone and MDDA patients. However, comorbid anxiety, especially psychic anxiety may contribute to extensive cognitive deficits in MDDA patients. Notably, anxiety symptoms only independently triggered executive dysfunction when eliminating effect of the severity of depression.

2.
Mol Med Rep ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31638202

RESUMO

Microglia serve important roles in chronic pain signal transduction pathways. Glia cells, especially microglia, seem to share mechanisms that lead to chronic pain and morphine­induced tolerance. Evidence has suggested that downregulating cytoskeleton activity in microglia provides pain relief in chronic pain and morphine tolerance. The purpose of the present study was to evaluate the effect of ethanol extracts of Hericium erinaceus (EHE) mycelium on morphine­induced BV2 microglial cell activation. BV2 cells were starved for 4 h in DMEM before being incubated with 100 ng/ml EHE for 30 min, followed by 1 µM morphine for 2 h. Subsequently, the cells were harvested and used for migration experiments and western blotting. The results showed that 1 µM morphine enhanced BV2 cell activation and chemotactic reaction, and it increased histone deacetylase 6 (HDAC6) expression and heat shock protein 90 (HSP90) deacetylation as well as HSP90 cleavage. Pretreatment with 100 ng/ml EHE significantly inhibited the morphine­stimulated effects on BV2 cells. The present study demonstrated that EHE inhibited morphine­induced BV2 activations by regulating the HDAC6/HSP90 deacetylation signal transduction pathway.

3.
ChemSusChem ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638336

RESUMO

The reliable and accurate quantification of ammonia in electrochemical and photochemical experiments has been a technical challenge owing to the extremely low concentration of generated ammonia, interference from trace amounts of cations and organic compounds, and ammonia contamination from various sources. As a result, overestimation and significant errors may happen in many research works. Herein, accuracy and precision of ion chromatography (IC) are evaluated at different pH; excellent performance with a low detection limit (<2 µg L-1 ) under acidic and neutral conditions is found, whereas the linearity is unsatisfactory in the low NH4 + concentration range (0-100 µg L-1 ) under alkaline conditions. High concentrations of Li+ and Na+ are difficult to separate from NH4 + in conventional IC, but this can be solved by employing a high-exchange-capacity column or gradient elution. The interference effects of 14 common transition metal cations and 6 common organic compounds on the quantification of ammonium with low-level concentration (500 µg L-1 ) using IC are systematically investigated, and the results demonstrate good robustness. The overestimation caused by ammonia contamination from reagent water, surroundings, and even the analytical grade of inorganic and organic reagents are confirmed and the results indicate the necessity to prepare and test fresh electrolyte solutions before each experiment, owing to the high sensitivity of acidic and neutral solutions to ammonia contamination from the surroundings. The ammonization of a Nafion membrane during experiments and the underestimation in quantification are also discussed. Finally, a reliable level of synthesized ammonia is identified and some recommendations are presented to improve the reliability and accuracy of ammonia quantification.

4.
Cancer Med ; 8(14): 6315-6325, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31486298

RESUMO

Endoscopic resection (ER) has been increasingly performed in the treatment of early gastric cancer (GC). However, lymph node metastasis (LNM) can cause treatment failure with ER, especially in T1b patients. Here, we attempted to develop a miRNA-based classifier to detect LNM in T1b patients. Based on high-throughput data from The Cancer Genome Atlas, we identified 20 miRNAs whose expression significantly changed in T1-2 GC with LNM vs T1-2 GC without LNM. We then developed a miRNA signature to predict LNM of T1b GC using the LASSO model and backward step wise elimination approach in a training cohort. Furthermore, the predictive accuracy of this classifier was validated in both an internal testing group of 63 patients and an external independent group of 114 patients. This systematic and comprehensive in silico study identified a 7-miRNA signature with an area under the receiver operating characteristic curve (AUROC) value of 0.843 in T1-2 GC and 0.911 in T1 EGC. The backward elimination was further used to develop a 4-miRNA (miR-153-3p, miR-708, miR-940 and miR-375) risk-stratification model in the training cohort with an AUROC value of 0.898 in cohort 2. When pathologic results were used as a reference, the risk model yielded AUROC values of 0.829 and 0.792 in two cohorts of endoscopic biopsy specimens. This novel miRNA-LNM classifier works better than the currently used pathologic criteria of ER in T1b EGC. This classifier could individualize the management of T1b patients and facilitate treatment decisions.

5.
EBioMedicine ; 47: 543-552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31420302

RESUMO

BACKGROUND: Current fMRI-based classification approaches mostly use functional connectivity or spatial maps as input, instead of exploring the dynamic time courses directly, which does not leverage the full temporal information. METHODS: Motivated by the ability of recurrent neural networks (RNN) in capturing dynamic information of time sequences, we propose a multi-scale RNN model, which enables classification between 558 schizophrenia and 542 healthy controls by using time courses of fMRI independent components (ICs) directly. To increase interpretability, we also propose a leave-one-IC-out looping strategy for estimating the top contributing ICs. FINDINGS: Accuracies of 83·2% and 80·2% were obtained respectively for the multi-site pooling and leave-one-site-out transfer classification. Subsequently, dorsal striatum and cerebellum components contribute the top two group-discriminative time courses, which is true even when adopting different brain atlases to extract time series. INTERPRETATION: This is the first attempt to apply a multi-scale RNN model directly on fMRI time courses for classification of mental disorders, and shows the potential for multi-scale RNN-based neuroimaging classifications. FUND: Natural Science Foundation of China, the Strategic Priority Research Program of the Chinese Academy of Sciences, National Institutes of Health Grants, National Science Foundation.

6.
Br J Psychiatry ; : 1-8, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31169117

RESUMO

BACKGROUND: Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.AimsTo investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia. METHOD: Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant. RESULTS: The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus-medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia. CONCLUSIONS: These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.Declaration of interestNone.

7.
Genome Biol ; 20(1): 104, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126314

RESUMO

A recent study on human structural variation indicates insufficiencies and errors in the human reference genome, GRCh38, and argues for the construction of a human pan-genome.


Assuntos
Genoma Humano , Variação Estrutural do Genoma , Genômica/normas , Humanos , Padrões de Referência
8.
Stem Cells Dev ; 28(16): 1116-1127, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31140357

RESUMO

Interkinetic nuclear migration (INM) is a process by which nuclei oscillate between the basal and apical surfaces of epithelial cells in coordination with the cell cycle. The cytoskeletal machinery including microtubules and actin has been reported to drive apical INM; however, the role of nuclear proteins in this process has yet to be fully elucidated. Here, we investigated the function of a SUN-domain protein, Sun1, in zebrafish. We found that zebrafish sun1 is highly expressed in the ventricular zone of the brain. Knocking down sun1 with antisense morpholino oligonucleotides reduced the abundance of nestin- and gfap-expressing neural stem cells and progenitor cells. The live-cell imaging results showed that sun1 morphant cells migrated toward the basal side during the S phase but failed to migrate apically during the G2 phase. On the contrary, the passive stochastic movement during the G2 phase was unaffected. Furthermore, down regulation of sun1 was shown to reduce the expression of genes associated with the Notch pathway, whereas the expression of genes in the Wnt pathway was less perturbed. Findings from this research suggest that the Sun1-mediated nucleo-cytoskeletal interaction contributes to apical nuclear migration, and may thus affect exposure to Notch signal, thereby altering the composition of the progenitor pool in the embryonic neurogenesis of zebrafish.

9.
PLoS One ; 14(5): e0217226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31100095

RESUMO

Erinacine A-enriched Hericium erinaceus mycelia is a well-established potential therapeutic agent for neurodegenerative disorders. However, the effect of erinacine A-enriched H. erinaceus mycelia on promoting longevity remains unclear. This is the first study to investigate the effect of erinacine A-enriched H. erinaceus mycelia on lifespan-prolonging activity in Drosophila melanogaster and senescence-accelerated P8 (SAMP8) mice. Two hundred D. melanogaster and 80 SAMP8 mice of both sexes were randomly divided into four groups and were administered with either the standard, low-dose, mid-dose, or high-dose erinacine A-enriched H. erinaceus mycelia. After treatment, the lifespan was measured in D. melanogaster, and the lifespan, food intake and oxidative damage were evaluated in SAMP8 mice. Results showed that supplementation with erinacine A-enriched H. erinaceus mycelia extended the lifespan in both D. melanogaster and SAMP8 by a maximum of 32% and 23%, respectively, compared to the untreated controls. Moreover, erinacine A-enriched H. erinaceus mycelia decreased TBARS levels and induced the anti-oxidative enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. Together, these findings suggest that erinacine A-enriched H. erinaceus mycelia supplement could promote longevity, mediated partly through the induction of endogenous antioxidants enzymes.

10.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022946

RESUMO

Erinacine S, so far known to have been produced only in Hericium erinaceus mycelia, has just recently been discovered and is able to reduce amyloid plaque growth and improve neurogenesis in aged brain of rats. However, few investigations have been conducted on the absorption, distribution, and excretion study of Erinacine S. This study aimed to investigate the absolute bioavailability, tissue distribution, and excretion of Erinacine S in H. Erinaceus mycelia in eight-week old Sprague-Dawley rats. After oral administration and intravenous administration of 2.395 g/kg body weight of the H. erinaceus mycelia extract (equivalent to 50 mg/kg body weight Erinacine S) and 5 mg/kg of Erinacine S, respectively, the absolute bioavailability was estimated as 15.13%. In addition, Erinacine S was extensively distributed in organs such as brain, heart, lung, liver, kidney, stomach, small intestine, and large intestine. The maximum concentration of Erinacine S was observed in the stomach, 2 h after the oral administration of H. erinaceus mycelia extract, whereas the maximum amount of Erinacine S found in other tissues were seen after 8 h. Total amount of unconverted Erinacine S eliminated in feces and urine in 24 h was 0.1% of the oral dosage administrated. This study is the first to show that Erinacine S can penetrate the blood-brain barrier of rats and thus support the development of H. erinaceus mycelia, for the treatment of neurological diseases.


Assuntos
Basidiomycota/química , Encéfalo/efeitos dos fármacos , Placa Amiloide/tratamento farmacológico , Sesterterpenos/administração & dosagem , Animais , Disponibilidade Biológica , Encéfalo/metabolismo , Modelos Animais de Doenças , Humanos , Micélio/química , Neurogênese/efeitos dos fármacos , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Ratos , Sesterterpenos/química , Sesterterpenos/metabolismo , Distribuição Tecidual/efeitos dos fármacos
11.
ACS Synth Biol ; 8(4): 621-632, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30955321

RESUMO

The mitochondria DNA (mtDNA) editing tool, zinc finger nucleases (ZFNs), transcription activator-like effector nuclease (TALENs), and clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system, is a promising approach for the treatment of mtDNA diseases by eliminating mutant mitochondrial genomes. However, there have been no reports of repairing the mutant mtDNA with homologous recombination strategy to date. Here, we show a mito-CRISPR/Cas9 system that mito-Cas9 protein can specifically target mtDNA and reduce mtDNA copy number in both human cells and zebrafish. An exogenous single-stranded DNA with short homologous arm was knocked into the targeting loci accurately, and this mutagenesis could be steadily transmitted to F1 generation of zebrafish. Moreover, we found some major factors involved in nuclear DNA repair were upregulated significantly by the mito-CRISPR/Cas9 system. Taken together, our data suggested that the mito-CRISPR/Cas9 system could be a useful method to edit mtDNA by knock-in strategy, providing a potential therapy for the treatment of inherited mitochondrial diseases.

12.
Nat Commun ; 10(1): 1784, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992455

RESUMO

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.


Assuntos
Genoma Humano/genética , Variação Estrutural do Genoma , Genômica/métodos , Haplótipos/genética , Algoritmos , Mapeamento Cromossômico/métodos , Bases de Dados Genéticas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação INDEL , Sequenciamento Completo do Genoma/métodos
13.
Int J Med Mushrooms ; 21(4): 401-411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002635

RESUMO

Recently, erinacine A-enriched Hericium erinaceus (EAHE) mycelia have demonstrated therapeutic efficacy in animal models of neurodegenerative disease, including Alzheimer and Parkinson disease. Despite promising results from animal models, there have been no reports on its toxicity after long-term consumption. Hence, the present study was designed to evaluate the safety of EAHE mycelia through a 13-week subchronic rodent feeding study. Following 13 weeks of EAHE mycelia feeding at dosages of 0, 875, 1750, and 2625 mg/kg body weight in both male and female Sprague-Dawley rats, findings revealed neither any mortalities nor noticeable toxicological effects in all the rats during the investigation period. Physiological parameters including body weight and feed consumption patterns were unaffected by EAHE mycelia administration. The hematological and biochemical parameters as well as histopathological studies revealed no significant differences between the treatment and control groups. Conclusively, the obtained results suggested that EAHE mycelia could be relatively unharmful when used over an extended period, supporting its safe use in food preparation.


Assuntos
Basidiomycota/química , Diterpenos/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Micélio/química , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade
14.
Ann Otol Rhinol Laryngol ; 128(7): 654-661, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30895824

RESUMO

OBJECTIVES: Liuzijue Qigong (LQG), a kind of traditional Chinese health exercise (TCHE), is not only widely used to strengthen physical fitness and maintain psychological well-being in the elderly but has also been utilized to help improve respiratory function. As respiratory support is an important driving force for speech production, it is logical to postulate that the LQG training method with 6 monosyllabic speech sounds, xu, he, hu, si, chui, and xi, can help individuals (1) experience a relaxing and natural state of speech production, (2) eliminate voice symptoms, and (3) improve their overall body function and mood. In the current study, we hypothesized that the LQG method with these 6 sounds can be effective in improving vocal function in subjects with unilateral vocal fold paralysis (UVFP) in comparison with a conventional voice therapy method. METHODS: A total of 48 patients with UVFP who met the inclusion criteria were randomly divided into 2 groups. Twenty-four subjects in the experimental group were trained with LQG, and those in the control group received conventional voice training (abdominal breathing and yawn-sign exercises) for a total of 4 sessions, twice a week. Patients in both groups were assessed with acoustic tests, the GRBAS scale, the Voice Handicap Index (VHI-10), and the Hospital Anxiety and Depression Scale (HADS) pre- and posttreatment. Statistical analysis was conducted using nonparametric tests and t tests. RESULTS: There existed significant changes in maximum phonation time (MPT), jitter, shimmer, normalized noise energy (NNE), GRBAS scores, VHI-10 scores, and grade of A in HADS scores pre- and posttreatment in both the experimental group and the control group ( P < .004). However, no significant changes were seen posttreatment between the 2 groups ( P > .05). CONCLUSIONS: LQG could help improve vocal function in UVFP patients as our preliminary data showed no significant differences between LQG and conventional voice therapy methods.


Assuntos
Medicina Tradicional Chinesa/métodos , Paralisia das Pregas Vocais/reabilitação , Treinamento da Voz , Adulto , Ansiedade/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Paralisia das Pregas Vocais/psicologia , Qualidade da Voz
15.
Pathol Res Pract ; 215(5): 963-976, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30904360

RESUMO

BACKGROUND: The role of miR-99a-3p in Head and neck squamous cell carcinoma (HNSCC) has not been reported. Therefore, in this study, we examined the expression level and its molecular mechanisms of miR-99a-3p in HNSCC. MATERIALS AND METHODS: MiR-99a-3p-related miRNA-chip and miRNA-sequencing data were collected. We then carried out meta-analyses to pool the standard mean difference (SMD) value and generate a summarized receiver operating characteristic (sROC) curve. MiR-99a-3p mimic was transfected into FaDu cells and those genes influenced by miR-99a-3p were gathered. The target genes were also predicted from 12 tools through miRwalk2.0, and combined with differentially expressed genes in HNSCC from the The Cancer Genome Atlas and Genotype-Tissue Expression sequencing databases. FunRich and DAVID were used for the pathway signaling analyses for the potential targets of miR-99a-3p in HNSCC. RESULTS: The SMD was -0.30 (95% CI: -0.51, -0.08) in the fixed-effect model and -0.28 (95% CI: -0.67, 0.10) in the random-effect model (I2 = 60%), indicating a reduced expression level of miR-99a-3p in HNSCC tissues based on 1167 cases. In the sROC curve, the area under the curve (AUC) was 0.77 (95% CI: 0.73, 0.81). The 251 potential targets of miR-99a-3p were enriched in several pathways related to cancer, with the "Pathways in cancer" standing at the top. vascular endothelial growth factor A was selected as an example with up-regulated trend in HNSCC tissues. CONCLUSION: MiR-99a-3p exhibits a significant lower expression status in HNSCC, and this reduced or deletion status promotes the malignant progression of HNSCC. However, its molecular mechanism is still unclear and requires further investigation.


Assuntos
MicroRNAs/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
16.
Biomaterials ; 206: 61-72, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30925289

RESUMO

Graphene quantum dots (GQDs) are well-known for its potential applications for bioimaging, biosensor, and drug carrier in biomedicine. GQDs are well characteristic of intrinsic peroxidase-like catalytic activity, which is proven effective in scavenging the free radicals, such assuperoxide anion, hydrogen peroxide, and hydroxyl radical. GQDs are also well praised for its low in vivo and in vitro toxicity. Here, we found that nitrogen-doped GQDs (N-GQDs) can strongly disturb redox-sensitive system via the selective inhibition of endogenous antioxidant enzyme activities in zebrafish. The enzyme activities or transcription levels of a battery of hemoproteins including catalase (CAT), superoxide dismutase (SOD), respiratory chain complex I, complex Ⅲ, hemoglobin (Hb), and myeloperoxidase (MPO), were significantly suppressed by N-GQDs. We also found that N-GQDs activated the cytochrome P450 monooxygenase (e.g. cyp1a) and the associated aryl-hydrocarbon receptor repressors (ahrr1 and ahrr2) in zebrafish embryos. Compared to the ultrasmall graphene oxide (USGO), N-GQDs exhibited stronger fluorescent permeability and tissue-specific bio-accumulative effects. Taken together, our findings highlighted that exposure to N-GQDs can disrupt endogenous antioxidant enzyme activities, possibly via the competitive inhibition of electron transfer process. Our results in this study provided solid data for biosafety evaluations of various types of GQDs, and created an alert for the future biomedical applications of N-GQDs.

17.
Adv Mater ; 31(12): e1807789, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30702774

RESUMO

In response to the call for safer high-energy-density storage systems, high-voltage solid-state Li metal batteries have attracted extensive attention. Therefore, solid electrolytes are required to be stable against both Li anode and high-voltage cathodes; nevertheless, the requirements still cannot be completely satisfied. Herein, a heterogeneous multilayered solid electrolyte (HMSE) is proposed to broaden electrochemical window of solid electrolytes to 0-5 V, through different electrode/electrolyte interfaces to overcome the interfacial instability problems. Oxidation-resistance poly(acrylonitrile) (PAN) is in contact with the cathode, while reduction tolerant polyethylene glycol diacrylate contacts with Li metal anode. A Janus and flexible PAN@Li1.4 Al0.4 Ge1.6 (PO4 )3 (80 wt%) composite electrolyte is designed as intermediate layer to inhibit dendrite penetration and ensure compact interface. Paired with LiNi0.6 Co0.2 Mn0.2 O2 and LiNi0.8 Co0.1 Mn0.1 O2 cathodes, which are rarely used in solid-state batteries, the solid-state Li metal batteries with HMSE exhibit excellent electrochemical performance including high capacity and long cycle life. Besides, the Li||Li symmetric batteries maintain a stable polarization less than 40 mV for more than 1000 h under 2 mA cm-2 and effective inhibition of dendrite formation. This study offers a promising approach to extend the applications of solid electrolytes for high-voltage solid-state Li metal batteries.

18.
Nat Genet ; 51(2): 354-362, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30643257

RESUMO

The human reference genome serves as the foundation for genomics by providing a scaffold for alignment of sequencing reads, but currently only reflects a single consensus haplotype, thus impairing analysis accuracy. Here we present a graph reference genome implementation that enables read alignment across 2,800 diploid genomes encompassing 12.6 million SNPs and 4.0 million insertions and deletions (indels). The pipeline processes one whole-genome sequencing sample in 6.5 h using a system with 36 CPU cores. We show that using a graph genome reference improves read mapping sensitivity and produces a 0.5% increase in variant calling recall, with unaffected specificity. Structural variations incorporated into a graph genome can be genotyped accurately under a unified framework. Finally, we show that iterative augmentation of graph genomes yields incremental gains in variant calling accuracy. Our implementation is an important advance toward fulfilling the promise of graph genomes to radically enhance the scalability and accuracy of genomic analyses.


Assuntos
Genoma Humano/genética , Genômica/métodos , Humanos , Polimorfismo de Nucleotídeo Único/genética , Alinhamento de Sequência/métodos , Análise de Sequência de DNA/métodos , Deleção de Sequência/genética , Sequenciamento Completo do Genoma/métodos
19.
Artigo em Inglês | MEDLINE | ID: mdl-30550872

RESUMO

Acid sphingomyelinase (ASM) is a membrane lipid hydrolase, acting to generate ceramide and regulate cell functions and inflammatory responses.The roles of ASM in mediating T cell functions are postulated whereas its function in regulation of macrophages remains uncertain. The study was performed to explore ASM activity in control of macrophage functions. RAW 264.7 cells were pretreated with desipramine, an ASM inhibitor, prior to LPS challenge in vitro. LPS initiated ASM activity in RAW 264.7 cells. Conversely, inhibition of ASM activity by desipramine diminished LPS induced ASM activities and TNF production of RAW 264.7 cells. The DSS colitis in mice was induced, and desipramine was administered to the mice two days post induction of colitis. Murine colitis was characterized by elevation of ASM activities in colon tissues. Desipramine administration overrode ASM activities in colon, and ameliorated DSS-induced colitis evidenced with the reduced disease activities and the decreased cytokine levels. Together, our data show a crucial role of ASM activity in regulation of macrophage functions and responses, and suggest that ASM represents a novel therapeutic approach for the management of immune diseases.


Assuntos
Colite/induzido quimicamente , Colite/enzimologia , Sulfato de Dextrana/farmacologia , Inibidores Enzimáticos/farmacologia , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Animais , Colite/tratamento farmacológico , Colite/imunologia , Colo/efeitos dos fármacos , Colo/imunologia , Citocinas/metabolismo , Inibidores Enzimáticos/uso terapêutico , Feminino , Imunidade Inata/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7
20.
Int J Mol Sci ; 19(12)2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30518074

RESUMO

In contrast to -1 programmed ribosomal frameshifting (PRF) stimulation by an RNA pseudoknot downstream of frameshifting sites, a refolding upstream RNA hairpin juxtaposing the frameshifting sites attenuates -1 PRF in human cells and stimulates +1 frameshifting in yeast. This eukaryotic functional mimicry of the internal Shine-Dalgarno (SD) sequence-mediated duplex was confirmed directly in the 70S translation system, indicating that both frameshifting regulation activities of upstream hairpin are conserved between 70S and 80S ribosomes. Unexpectedly, a downstream pseudoknot also possessed two opposing hungry codon-mediated frameshifting regulation activities: attenuation of +1 frameshifting and stimulation of a non-canonical -1 frameshifting within the +1 frameshift-prone CUUUGA frameshifting site in the absence of release factor 2 (RF2) in vitro. However, the -1 frameshifting activity of the downstream pseudoknot is not coupled with its +1 frameshifting attenuation ability. Similarly, the +1 frameshifting activity of the upstream hairpin is not required for its -1 frameshifting attenuation function Thus, each of the mRNA duplexes flanking the two ends of a ribosomal mRNA-binding channel possesses two functions in bi-directional ribosomal frameshifting regulation: frameshifting stimulation and counteracting the frameshifting activity of each other.

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