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1.
Pharmacol Res ; 169: 105682, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34019980

RESUMO

The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAAR), and the down-regulation of its biosynthesis have been attributed to the development of mood disorders, such as depression, anxiety and post-traumatic stress disorder (PTSD). ALLO mediated depression/anxiety involves GABAergic mechanisms and appears to be related to brain-derived neurotrophic factor (BDNF), dopamine receptor, glutamate neurotransmission, and Ca2+ channel. In the clinical, brexanolone, as a newly developed intravenous ALLO preparation, has been approved for the treatment of postpartum depression (PPD). In addition, traditional antidepressants such as selective serotonin reuptake inhibitor (SSRI) could reverse ALLO decline. Recently, the translocation protein (TSPO, 18 kDa), which involves in the speed-limiting step of ALLO synthesis, and ALLO derivatization have been identified as new directions for antidepressant therapy. This review provides an overview of ALLO researches in animal model and patients, discusses its role in the development and treatment of depression/anxiety, and directs its therapeutic potential in future.

2.
Shock ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33900712

RESUMO

BACKGROUND: Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that plays an important role in endothelial injury and the inflammatory response. Experimental models have implicated ANGPTL4 in acute respiratory distress syndrome (ARDS), but its impact on the progression of ARDS is unclear. METHODS: Paired bronchoalveolar lavage fluid (BALF) and serum samples were obtained from patients with ARDS (n = 56) within 24 h of diagnosis and from control subjects (n = 32). ANGPTL4, angiopoietin-2, interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were measured by magnetic Luminex assay. BALF albumin (BA) and serum albumin (SA) were evaluated by enzyme-linked immunosorbent assay. RESULTS: BALF and serum ANGPTL4 concentrations were higher in patients with ARDS than in controls and were even higher in survivors than in non-survivors. The serum ANGPTL4 level was higher in indirect (extrapulmonary) ARDS than in direct (pulmonary) ARDS. Furthermore, BALF and serum ANGPTL4 levels correlated well with angiopoietin-2, IL-6, and TNF-α levels in BALF and serum. BALF ANGPTL4 was positively correlated with the BA/SA ratio (an indicator of pulmonary vascular permeability), and serum ANGPTL4 was associated with the severity of multiple organ dysfunction syndrome based on SOFA and APACHE II scores. Moreover, serum ANGPTL4 was better able to predict 28-day ARDS-related mortality (AUC 0.746, p < 0.01) than the APACHE II score or PaO2/FiO2 ratio. Serum ANGPTL4 was identified as an independent risk factor for mortality in a univariate Cox regression model (p < 0.001). CONCLUSION: ANGPTL4 levels were elevated in patients with ARDS and significantly correlated with disease severity and mortality. ANGPTL4 may be a novel prognostic biomarker in ARDS.

3.
Int Immunopharmacol ; 95: 107570, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33773208

RESUMO

Cell-cell junctions are critical for the maintenance of cellular as well as tissue polarity and integrity. Dysfunction of airway epithelial barrier has been shown to be involved in the pathogenesis of acute lung injury (ALI). Yet the role of phosphatidylinositol 3-kinase delta (PI3Kδ) in dysregulation of airway epithelial barrier integrity in ALI has not been addressed. Mice were subjected to intratracheal instillation of lipopolysaccharide (LPS) to generate a ALI model. Two pharmacological inhibitors of PI3Kδ, IC87114 and AMG319, were respectively given to the mice. Expression of p110δ and its downstream substrate phospho-AKT (Ser473) was increased in LPS-exposed lungs. These increases were inhibited by IC87114 or AMG319. LPS led to pronounced lung injury that was accompanied by significant airway neutrophil recruitment and bronchial epithelial morphological alterations 72 h after exposure. We also found compromised expression of adherens junction protein E-cadherin and tight junction protein claudin-2 in the airway epithelial cells. Treatment with either IC87114 or AMG319 not only attenuated LPS-induced edema, lung injury and neutrophilc inflammation, reduced total protein concentration and IL-6, TNF-α secretion in BALF, but also restored epithelial E-cadherin and claudin-2 expression. In summary, our results showed that LPS can induce a delayed effect on airway epithelial barrier integrity that is mediated by PI3Kδ in a mouse model of ALI.


Assuntos
Lesão Pulmonar Aguda/imunologia , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Lesão Pulmonar Aguda/induzido quimicamente , Adenina/análogos & derivados , Adenina/farmacologia , Adenosina/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Caderinas/imunologia , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Claudinas/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Quinazolinas/farmacologia , Quinolinas/farmacologia
4.
Am J Med Sci ; 361(3): 319-326, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33541709

RESUMO

BACKGROUND: We aimed to explore the biomarkers associated with atrial fibrillation (AF) with mitral regurgitation (MR). METHODS: The gene expression profile data GSE115574 were downloaded from Gene Expression Omnibus database, which were obtained from patients with degenerative MR with AF and sinus rhythm (SR). The differentially expressed genes (DEGs) in samples of AF with MR compared with those of SR with MR were selected, followed by functional enrichment analysis, protein-protein interaction (PPI) network analysis, transcription factor (TF) prediction, and drug-gene interaction prediction. RESULTS: By comparing the genes' expression profiles between AF with MR and SR with MR, 379 DEGs were obtained. The upregulated genes, such as NMNAT2, LDHB, and hexosaminidase subunit beta (HEXB), were significantly enriched in metabolic pathways. Hub genes, such as amyloid beta precursor protein (APP), CDH2, SPP1, and STC2, were significantly associated with functions related to extracellular matrix organization and vitamin D response. Additionally, two TFs, PRDM3 and LSM6, were predicted for the key module genes. APP predicted the most drug molecules, that is, 22 molecules, and SPP1 predicted 10 drug molecules. CONCLUSIONS: Dysregulation of the metabolic pathway may play a critical role in AF with MR. Changes in functions related to the extracellular matrix and vitamin D response may also be associated with AF progression in patients with MR. Furthermore, APP, STC2, and SPP1 may serve as potential therapeutic targets of AF.


Assuntos
Fibrilação Atrial/genética , Biomarcadores/análise , Insuficiência da Valva Mitral/genética , Transcriptoma , Fibrilação Atrial/metabolismo , Regulação da Expressão Gênica , Redes e Vias Metabólicas/genética , Insuficiência da Valva Mitral/metabolismo
5.
Neuroimage Clin ; 30: 102572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33548865

RESUMO

Episodic memory (EM) deficit is the core cognitive dysfunction of amnestic mild cognitive impairment (aMCI). However, the episodic retrieval pattern detected by functional MRI (fMRI) appears preserved in aMCI subjects. To address this discrepancy, simultaneous electroencephalography (EEG)-fMRI recording was employed to determine whether temporal dynamics of brain episodic retrieval activity were disturbed in patients with aMCI. Twenty-six aMCI and 29 healthy control (HC) subjects completed a word-list memory retrieval task during simultaneous EEG-fMRI. The retrieval success activation pattern was detected with fMRI analysis, and the familiarity- and recollection-related components of episodic retrieval activity were identified using event-related potential (ERP) analysis. The fMRI-constrained ERP analysis explored the temporal dynamics of brain activity in the retrieval success pattern, and the ERP-informed fMRI analysis detected fMRI correlates of the ERP components related to familiarity and recollection processes. The two groups exhibited similar retrieval success patterns in the bilateral posteromedial parietal cortex, the left inferior parietal lobule (IPL), and the left lateral prefrontal cortex (LPFC). The fMRI-constrained ERP analysis showed that the aMCI group did not exhibit old/new effects in the IPL and LPFC that were observed in the HC group. In addition, the aMCI group showed disturbed fMRI correlate of ERP recollection component that was associated with inferior EM performance. Therefore, in this study, we identified disturbed temporal dynamics in episodic retrieval activity with a preserved spatial activity pattern in aMCI. Taken together, the simultaneous EEG-fMRI technique demonstrated the potential to identify individuals with a high risk of cognitive deterioration.

6.
Inflamm Res ; 70(4): 445-457, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33609142

RESUMO

OBJECTIVE AND DESIGN: Diabetic retinopathy (DR) is one of the most serious microvascular complications of diabetes mellitus (DM). MicroRNAs (miRNAs) have been discovered to play a crucial role in DR, but the mechanisms underlying the effects of miR-301a-3p on DR are poorly understood. This paper was designed to explore the possible role of miR-301a-3p in DR. METHODS: The diabetic rat model was established by a single intraperitoneal injection of streptozotocin (STZ). The effects of miR-301a-3p on the biological functions of HRECs were determined through a series of experiments in vitro/vivo. RESULTS: The results revealed that interference with miR-301a-3p could decrease the expressions of inflammatory factors and apoptosis in the retinal tissue of DR. Furthermore, it can alleviate the oxidative stress in DR serum, reduce VEGF expression, increase endothelial cell marker expression, and inhibit (High Glucose) HG-induced apoptosis of HRECs. Six-transmembrane epithelial antigen of prostate 4 (STEAP4) was the target of miR-301a-3p. All the effects of miR-301a-3p in DR model were reversed by STEAP4 inhibitor. CONCLUSION: miR-301a-3p promotes diabetic retinopathy via regulation of STEAP4. The findings in this study may provide a vital reference for the drug research and development in DR treatment.

7.
Front Cell Infect Microbiol ; 10: 587269, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324574

RESUMO

The pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing great threats to the world in many aspects. Effective therapeutic and preventive approaches including drugs and vaccines are still unavailable although they are in development. Comprehensive understandings on the life logic of SARS-CoV-2 and the interaction of the virus with hosts are fundamentally important in the fight against SARS-CoV-2. In this review, we briefly summarized the current advances in SARS-CoV-2 research, including the epidemic situation and epidemiological characteristics of the caused disease COVID-19. We further discussed the biology of SARS-CoV-2, including the origin, evolution, and receptor recognition mechanism of SARS-CoV-2. And particularly, we introduced the protein structures of SARS-CoV-2 and structure-based therapeutics development including antibodies, antiviral compounds, and vaccines, and indicated the limitations and perspectives of SARS-CoV-2 research. We wish the information provided by this review may be helpful to the global battle against SARS-CoV-2 infection.


Assuntos
COVID-19/virologia , SARS-CoV-2/fisiologia , Animais , Anticorpos Monoclonais/química , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Interações Hospedeiro-Patógeno , Humanos , Pandemias/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas de DNA/imunologia , Vacinas Virais/imunologia
8.
Phytother Res ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33111362

RESUMO

Ligustilide is a phenolic compound isolated from Asian plants of Umbelliferae family. This study was aimed at exploring the neuroprotective effects of Ligustilide from the perspective of endoplasmic reticulum stress (ERS) and autophagy. The Alzheimer's disease (AD) cell models were constructed by SH-SY5Y cell line, which was exposed to 20 µM Aß25-35 . CCK-8 was used to evaluate the cell viability of Ligustilide on AD cell model. Hoechst staining and LysoTracker Red were used to test the cell apoptosis and Lysosome function, respectively. ERS in living cells were detected by Thioflavin T. The expression of autophagy-related proteins (LC3B-II/I, P62/SQSTM1, Beclin1, and Atg5), ERS marker proteins (PERK, GRP78, and CHOH), and apoptosis proteins (Bax, Bcl-2, and Caspase-12) were analyzed by Western blot analyses. Aß25-35 could induce ERS and autophagy in a time-dependent manner in SH-SY5Y cells. We demonstrated that Ligustilide significantly decreased the rate of apoptosis, and improved the viability of cells. Simultaneously, Ligustilide effectively modulated ERS via inhibiting the over-activation of GRP78/PERK/CHOP signaling pathway. In addition, Ligustilide alleviated the accumulation of autophagy vacuoles, reduced the ratio of LC3B-II/I and the level of P62/SQSTM1. Ligustilide significantly up-regulated lysosomal acidity and the expression of Cathepsin D (CTSD). Ligustilide could rescue lysosomal function to promote autophagy flux and inhibit the over-activation of ERS. This finding may contribute to the development of new therapeutic strategies for AD.

9.
Mol Ecol Resour ; 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040437

RESUMO

Elephant grass (2n = 4x = 28; Cenchrus purpureus Schumach.), also known as Napier grass, is an important forage grass and potential energy crop in tropical and subtropical regions of Asia, Africa and America. However, no study has yet reported a genome assembly for elephant grass at the chromosome scale. Here, we report a high-quality chromosome-scale genome of elephant grass with a total size of 1.97 Gb and a 1.5% heterozygosity rate, obtained using short-read sequencing, single-molecule long-read sequencing and Hi-C chromosome conformation capture. Evolutionary analysis showed that subgenome A' of elephant grass and pearl millet may have originated from a common ancestor more than 3.22 million years ago (MYA). Further, allotetraploid formation occurred at approximately 6.61 MYA. Syntenic analyses within elephant grass and with other grass species indicated that elephant grass has experienced chromosomal rearrangements. We found that some key enzyme-encoding gene families related to the biosynthesis of anthocyanidins and flavonoids were expanded and highly expressed in leaves, which probably drives the production of these major anthocyanidin compounds and explains why this elephant grass cultivar has a high anthocyanidin content. In addition, we found a high copy number and transcript levels of genes involved in C4 photosynthesis and hormone signal transduction pathways that may contribute to the fast growth of elephant grass. The availability of elephant grass genome data advances our knowledge of the genetic evolution of elephant grass and will contribute to further biological research and breeding as well as for other polyploid plants in the genus Cenchrus.

10.
Exp Ther Med ; 20(5): 70, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32963600

RESUMO

Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(9): 958-961, 2020 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-32820507

RESUMO

OBJECTIVE: To determine the carrier rate of deafness-related genetic variants among 53 873 newborns from Zhengzhou. METHODS: Heel blood samples of the newborns were collected with informed consent from the parents, and 15 loci of 4 genes related to congenital deafness were detected by microarray. RESULTS: In total 2770 newborns were found to carry deafness-related variants, with a carrier rate of 5.142%. 1325 newborns (2.459%) were found to carry heterozygous variants of the GJB2 gene, 1071 (1.988%) were found with SLC26A4 gene variants, 205 were found with GJB3 gene variants (0.381%), and 120 were found with 12S rRNA variants (0.223%). Five newborns have carried homozygous GJB2 variants, two have carried homozygous SLC26A4 variants, five have carried compound heterozygous GJB2 variants, and four have carried compound heterozygous SLC26A4 variants. 33 neonates have carried heterozygous variants of two genes at the same time. CONCLUSION: The carrier rate of deafness-related variants in Zhengzhou, in a declining order, is for GJB2, SLC26A4, GJB3 and 12S rRNA. The common variants included GJB2 235delC and SLC26A4 IVS7-2A>G, which are similar to other regions in China. To carry out genetic screening of neonatal deafness can help to identify congenital, delayed and drug-induced deafness, and initiate treatment and follow-up as early as possible.


Assuntos
Coloboma/genética , Conexinas , Heterozigoto , Diagnóstico Pré-Natal , Insuficiência Renal/genética , Refluxo Vesicoureteral/genética , China , Coloboma/diagnóstico , Conexinas/genética , Análise Mutacional de DNA , Surdez/genética , Feminino , Feto , Homozigoto , Humanos , Recém-Nascido , Mutação , Fenótipo , Gravidez , Insuficiência Renal/diagnóstico , Transportadores de Sulfato/genética , Refluxo Vesicoureteral/diagnóstico
12.
J Med Virol ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32644223

RESUMO

To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). A retrospective cohort of COVID-19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8-14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5-18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5-27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19-2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID-19 patients.

13.
Dermatol Ther ; : e13993, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648291

RESUMO

In-depth analysis on the rambling genes of psoriasis may help to identify the pathologic mechanism of this disease. However, this has seldom been performed. Using bioinformatic approaches, we analyzed four gene expression profiles in gene expression omnibus (GEO) database, identified the differentially expressed genes (DEGs), and found out the overlapping DEGs (common DEGs, CDEGs) in the above 4 profiles. The CDEGs were further subjected to Gene Ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network analysis, and hub genes were ranked. We identified 139 CDEGs associated with a variety of GO processes including keratinization, immune and inflammatory responses, and type 1 interferon signaling pathway. These CDEGs were enriched in a variety of KEGG processes, including cytokine-cytokine receptor interaction and chemokine signaling. PPI analysis showed that seven genes (HERC6, ISG15, MX1, RSAD2, OAS2, OASL, OAS3) were likely the novel hub genes of psoriasis. RT-qPCR identified that five (ISG15, MX1, OAS2, OASL, and OAS3) of the seven predicted hub genes were overexpressed in TNF-α stimulated HaCaT cell lines, a result quite consistent with the predictions. The study provides new information in exploring the mechanisms and therapeutic targets of psoriasis. This article is protected by copyright. All rights reserved.

14.
Drug Des Devel Ther ; 14: 1705-1716, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440096

RESUMO

Purpose: Chlorogenic acid (CGA), a phenolic acid isolated from fruits and vegetables, has been established to have neuroprotective properties in relation to Alzheimer's disease (AD). However, the precise mechanism by which CGA prevents cognitive deficits in AD has not been well studied. This study aimed to explore the potential molecular mechanism of CGA action using an Aß25-35-induced SH-SY5Y neuron injury and cogxnitive deficits model in APP/PS1 mice. Methods: Three-month-old male APP/PS1 double transgenic mice and a human neuroblastoma cell line (SH-SY5Y) were used to assess the effects of CGA on AD in vivo and in vitro, respectively. Cognitive function in mice was measured using a Morris water maze (MWM) test. Hematoxylin and eosin, monodansylcadaverine fluorescence, LysoTracker Red (LTR), and immunofluorescence staining were used to evaluate the morphological changes in vivo and in vitro. The protein expressions of autophagy markers (LC3B-II/LC3B-I, p62/SQSTM, beclin1 and Atg5) and lysosomal-function-related markers (cathepsin D, mTOR, p-mTOR P70S6K, p-p70s6k and TFEB) were analyzed with Western blot analyses. Results: CGA treatment significantly improved spatial memory, relieved neuron damage, and inhibited autophagy in APP/PS1 mice (P<0.05). Moreover, CGA notably suppressed autophagosome production and enhanced autophagy flux in SH-SY5Y cells induced by Aß25-35 (P<0.05). Further analysis showed that CGA markedly promoted lysosomal activity, and this was accompanied by upregulated cathepsin D protein expression, which was induced by the mTOR/TFEB signaling pathway in APP/PS1 mice and Aß25-35-exposed SH-SY5Y cells (P<0.05). Conclusion: CGA treatment restored autophagic flux in the brain and alleviated cognitive impairments in APP/PS1 mice via enhanced activation of the mTOR/TFEB signaling pathway.

15.
Sci Total Environ ; 729: 138753, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32375068

RESUMO

Per- and polyfluoroalkyl substances (PFASs) are emerging global environmental contaminants. Exploring the occurrence and environmental behavior of PFASs in the aquatic environment is a key step in solving global fluorine chemical pollution problems. In this study, surface water, pore water, and sediment were collected from the main tributary and the middle and lower reaches of the Daling River, adjacent to the Fuxin fluorochemical manufacturing facilities in Liaoning Province in China, to elucidate the occurrence and partition behavior of PFASs. The total concentrations of PFASs ranged from 48.4 to 4578 ng/L in the overlying water, from 173 to 9952 ng/L in the pore water, and from 2.16 to 40.3 ng/g dw in the sediment fraction. Generally, perfluorobutanoic acid (PFBA) and perfluorobutane sulfonate (PFBS) were the predominant congeners in the samples, with the mean relative content fractions being almost consistently >40% in the dissolved phase and >25% in the sediment. Hexafluoropropylene oxide dimer acid (HFPO-DA) and chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) were detected, albeit at low levels. In addition, the detection frequency and the contribution of legacy long-chain PFASs in sediment were higher than those in the overlying water and pore water. Except for perfluorohexane sulfonate (PFHxS), the concentrations of the alternative PFASs in the pore water were higher than in the overlying water. The organic carbon fraction was a more important controlling factor for PFAS sediment levels than cations content. As with legacy long-chain PFASs, HFPO-DA and 6:2 Cl-PFESA tended to partition into the solid phase, whereas short-chain PFASs were readily distributed in the aqueous phase. Such research results will be helpful in modeling the transport and fate of PFASs released by point sources into coastal waters through rivers and in developing effective risk assessment and management strategies for the control of PFAS pollution.

16.
Psychol Med ; : 1-9, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32308167

RESUMO

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is characterized by delayed P300 latency and reduced grey matter (GM) volume, respectively. The relationship between the features in aMCI is unclear. This study was to investigate the relationship between the altered P300 latency and the GM volume in aMCI. METHODS: Thirty-four aMCI and 34 well-matched normal controls (NC) were studied using electroencephalogram during a visual oddball task and scanned with MRI. Both tests were finished in the same day. RESULTS: As compared with the NC group, the aMCI group exhibited delayed P300 latency in parietal cortex and reduced GM volumes in bilateral temporal pole and left hippocampus/parahippocampal gyrus. A remarkable negative correlation was found between delayed P300 latency and reduced left hippocampal volume only in the aMCI group. Interestingly, the mediating analysis found P300 latency significantly mediated the association between right supramarginal gyrus volume and information processing speed indicated by Stroop Color and Word Test A scores. CONCLUSIONS: The association between delayed P300 latency and reduced left hippocampal volume in aMCI subjects suggests that reduced left hippocampal volume may be the potential structural basis of delayed P300 latency.

17.
Appl Environ Microbiol ; 86(11)2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32245758

RESUMO

The type IX secretion system (T9SS), which is involved in pathogenicity, motility, and utilization of complex biopolymers, is a novel protein secretion system confined to the phylum Bacteroidetes Cytophaga hutchinsonii, a common cellulolytic soil bacterium belonging to the phylum Bacteroidetes, can rapidly digest crystalline cellulose using a novel strategy. In this study, the deletion mutant of chu_0174 (gldN) was obtained using PY6 medium supplemented with Stanier salts. GldN was verified to be a core component of C. hutchinsonii T9SS, and is indispensable for cellulose degradation, motility, and secretion of C-terminal domain (CTD) proteins. Notably, the ΔgldN mutant showed significant growth defects in Ca2+- and Mg2+-deficient media. These growth defects could be relieved by the addition of Ca2+ or Mg2+ The intracellular concentrations of Ca2+ and Mg2+ were markedly reduced in ΔgldN These results demonstrated that GldN is essential for the acquisition of trace amounts of Ca2+ and Mg2+, especially for Ca2+ Moreover, an outer membrane efflux protein, CHU_2807, which was decreased in abundance on the outer membrane of ΔgldN, is essential for normal growth in PY6 medium. The reduced intracellular accumulation of Ca2+ and Mg2+ in the Δ2807 mutant indicated that CHU_2807 is involved in the uptake of trace amounts of Ca2+ and Mg2+ This study provides insights into the role of T9SS in metal ion assimilation in C. hutchinsonii IMPORTANCE The widespread Gram-negative bacterium Cytophaga hutchinsonii uses a novel but poorly understood strategy to utilize crystalline cellulose. Recent studies showed that a T9SS exists in C. hutchinsonii and is involved in cellulose degradation and motility. However, the main components of the C. hutchinsonii T9SS and their functions are still unclear. Our study characterized the function of GldN, which is a core component of the T9SS. GldN was proved to play vital roles in cellulose degradation and cell motility. Notably, GldN is essential for the acquisition of Ca2+ and Mg2+ ions under Ca2+- and Mg2+-deficient conditions, revealing a link between the T9SS and the metal ion transport system. The outer membrane abundance of CHU_2807, which is essential for Ca2+ and Mg2+ uptake in PY6 medium, was affected by the deletion of GldN. This study demonstrated that the C. hutchinsonii T9SS has extensive functions, including cellulose degradation, motility, and metal ion assimilation, and contributes to further understanding of the function of the T9SS in the phylum Bacteroidetes.


Assuntos
Proteínas de Bactérias/genética , Celulose/metabolismo , Cytophaga/fisiologia , Íons/metabolismo , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/metabolismo
18.
Soft Matter ; 16(16): 3869-3881, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32236197

RESUMO

Diffusion is an essential and fundamental means of transport of substances on cell membranes, and the dynamics of biomembranes plays a crucial role in the regulation of numerous cellular processes. The understanding of the complex mechanisms and the nature of particle diffusion have a bearing on establishing guidelines for the design of efficient transport materials and unique therapeutic approaches. Herein, this review article highlights the most recent advances in investigating diffusion dynamics of nanoscale objects on biological membranes, focusing on the approaches of tailored computer simulations and theoretical analysis. Due to the presence of the complicated and heterogeneous environment on native cell membranes, the diffusive transport behaviors of nanoparticles exhibit unique and variable characteristics. The general aspects and basic theories of normal diffusion and anomalous diffusion have been introduced. In addition, the influence of a series of external and internal factors on the diffusion behaviors is discussed, including particle size, membrane curvature, particle-membrane interactions or particle-inclusion, and the crowding degree of membranes. Finally, we seek to identify open problems in the existing experimental, simulation, and theoretical research studies, and to propose challenges for future development.

19.
J Gerontol A Biol Sci Med Sci ; 75(4): 664-670, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-31336382

RESUMO

To identify whether platelet amyloid-ß protein precursor (AßPP) ratio, phosphorylated-tau (P-tau) 231, P-tau181, and serine 396 and 404 (Ser396/404) phosphorylated tau are potential peripheral indicators for early Alzheimer's disease (AD). Forty-three amnesic mild cognitive impairment (aMCI) patients and 45 normal controls were recruited. Peripheral venous blood was drawn and platelets were collected and evaluated for potential indicators by Western blot analysis. Subsequent meta-analysis was completed on these selected indicators. In platelets of aMCI patients, the AßPP ratio level was significantly lower and levels of P-tau231 and Ser396/404 phosphorylated tau were significantly higher. Moreover, in aMCI patients, a negative correlation was observed between platelet P-tau231 level and the Trail Making Tests A score, and it was found that higher platelet P-tau231 levels significantly associated with a worse performance of information processing speed. Furthermore, values of the area under the curve of platelet P-tau231 and Ser396/404 phosphorylated tau were 0.624 and 0.657, respectively. Finally, a meta-analysis indicated platelet AßPP ratio level was significantly lower in MCI cohorts. In conclusion, platelets of aMCI subjects showed a lower AßPP ratio and higher levels of P-tau231 and Ser396/404 phosphorylated tau when compared to normal controls, which may be critical in identifying early AD.

20.
Brain Topogr ; 33(2): 255-266, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31691911

RESUMO

Motor imagery is considered as an ideal window to observe neural processes of action representations. Behavioral evidence has indicated an alteration of motor imagery in amnestic mild cognitive impairment (aMCI). However, it still remains unclear on the altered neurophysiological processing mechanism of motor imagery and whether this mechanism links the abnormal biological basis of motor imagery with impaired cognition in aMCI. This study was to investigate the altered neurophysiological processing mechanism of motor imagery and to examine the relationships between this knowledge and the altered structural basis of motor imagery with impaired cognition in aMCI. A hand mental rotation paradigm was used to manipulate the processing of motor imagery while event-related brain potentials (ERPs) were recorded and gray matter (GM) voxel-based morphometry was performed in 20 aMCI and 29 healthy controls. Compared with controls, aMCI exhibited lower ERP amplitudes in parietal cortex and higher ERP amplitudes in frontal cortex during motor imagery. In addition, aMCI showed reduced GM volumes in cerebellum posterior lobe, insula and hippocampus/parahippocampal gyrus, and increased GM volumes in middle cingulate gyrus and superior frontal gyrus. Most importantly, increased ERP amplitude significantly mediated the association between increased GM and cognition. This study provided a novel evidence for the relationships between the electrophysiological processing mechanism and structural basis of motor imagery with impaired cognition in aMCI. It suggests that improving neural activity by stimulating the frontal lobe can potentially contribute to acquire motor imagery skills for neurological rehabilitation in aMCI subjects.


Assuntos
Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Fenômenos Eletrofisiológicos , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Imaginação/fisiologia , Movimento , Idoso , Encéfalo/fisiopatologia , Mapeamento Encefálico , Cognição , Feminino , Hipocampo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Temporal
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