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1.
EBioMedicine ; 52: 102660, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32062357

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have been reported to be involved in central nervous system (CNS) diseases and to have a close connection with neuronal development. However, the role of circRNAs in neural stem cell (NSC) differentiation and the treatment of ischaemic stroke remains unknown. METHODS: Ischaemic stroke was induced in mice using transient middle cerebral artery occlusion (tMCAO). NSCs were transducted with circHIPK2 siRNA (si-circHIPK2-NSCs) or vehicle control (si-circCon-NSCs) and microinjected into lateral ventricle of brain at 7 d post-tMCAO. Magnetic resonance imaging (MRI) was used to detect brain damage, and functional deficits were evaluated with sensorimotor behavioural tests. The distribution of the transplanted NSCs was investigated by near-infrared fluorescence imaging (NIF) and immunofluorescence. The neural plasticity of si-circHIPK2-NSCs was verified by western blot and immunofluorescence in vivo and in vitro. FINDINGS: We investigated the role of circHIPK2 in NCS differentiation. In vitro, silencing of circHIPK2 facilitated NSCs directionally differentiated to neurons but had no effect on the differentiation to astrocytes. In vivo, microinjected NSCs could migrate to the ischaemic hemisphere after stroke induction. Si-circHIPK2-NSCs increased neuronal plasticity in the ischaemic brain, conferred long-lasting neuroprotection, and significantly reduced functional deficits. INTERPRETATIONS: Si-circHIPK2 regulates NSC differentiation, and microinjection of si-circHIPK2-NSCs exhibits a promising therapeutic strategy to neuroprotection and functional recovery after stroke. FUNDING: The National Key Research and Development Program of China; the International Cooperation and Exchange of the National Natural Science Foundation of China; the National Natural Science Foundation of China; the Jiangsu Innovation & Entrepreneurship Team Program.

2.
PLoS One ; 15(1): e0225481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910436

RESUMO

Microvesicles are small lipid, bilayer structures (20-400 nm in diameter) secreted by bacteria, fungi, archaea and parasites involved in inter-bacterial communication and host-pathogen interactions. Lactobacillus reuteri DSM-17938 (DSM) has been shown to have clinical efficacy in the treatment of infantile colic, diarrhea and constipation. We have shown previously that luminal administration to the mouse gut promotes reduction of jejunal motility but increases that in the colon. The production of microvesicles by DSM has been characterized, but the effect of these microvesicles on gastrointestinal motility has yet to be evaluated. To investigate a potential mechanism for the effects of DSM on the intestine, the bacteria and its products have here been tested for changes in velocity, frequency, and amplitude of contractions in intact segments of jejunum and colon excised from mice. The effect of the parent bacteria (DSM) was compared to the conditioned media in which it was grown, and the microvesicles it produced. The media used to culture the bacteria (broth) was tested as a negative control and the conditioned medium was tested after the microvesicles had been removed. DSM, conditioned medium, and the microvesicles all produced comparable effects in both the jejunum and the colon. The treatments individually decreased the velocity and frequency of propagating contractile cluster contractions in the jejunum and increased them in the colon to a similar degree. The broth control had little effect in both tissues. Removal of the microvesicles from the conditioned medium almost completely eradicated their effect on motility in both tissues. These results show that the microvesicles from DSM alone can completely reproduce the effects of the whole bacteria on gut motility. Furthermore, they suggest a new approach to the formulation of orally active bacterial therapeutics and offer a novel way to begin to identify the active bacterial components.

3.
BMC Ophthalmol ; 20(1): 10, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906917

RESUMO

BACKGROUND: Developing objective and repeatable indicators to evaluate the efficacy of PVRL treatment is important. The quantification of vitreous cells is a traditional criterion; however slight changes are difficult to ascertain. Spectral domain optical coherence tomography (SD-OCT) is objective, repeatable, and easily explained. The purpose of this study is to provide a longitudinal observation of OCT in PVRL treated with intravitreal injections of methotrexate (MTX) and to evaluate the utility of OCT in monitoring responsiveness of PVRL to treatment. METHODS: The medical records of patients with biopsy-positive PVRL attending our hospital between January 2016 and September 2017 who received intravitreal injections of MTX were included in this study. Pre- and post-treatment OCT images were reviewed independently by two researchers. RESULTS: Of the 24 cases reviewed, 10 patients (18 eyes) were included. SD-OCT abnormalities at the initial visit included vitreous cells (18/18), OR (outer retina) fuzzy borders (12/18), PED (pigment epithelium detachments) (9/18), subretinal hyperreflective infiltration (3/18), intraretinal infiltration (8/18), and SRF (subretinal fluid) (4/18). Post induction treatment, SRF in cases with RD (retinal detachment) was absorbed, and subretinal fibrosis appeared. Other lesions were significantly reduced. Post consolidation treatment, OR fuzzy borders, PED and SRF disappeared in 2 eyes, intraretinal infiltration disappeared in 1 eye, and other abnormalities further improved. Additionally, retinal fibrosis was observed in 3 eyes. One month post maintenance treatment, all abnormalities observed at the first visit vanished. At the last visit, OCT showed subretinal fibrosis and in 3 eyes (16.7%), the disruption of outer retina in 9 eyes (50%) and thinning of the whole layer in 4 eyes (22.2%). CONCLUSIONS: Our observations reveal that characteristic OCT features in PVRL patients can reduce gradually and finally vanish with therapy. We propose that SD-OCT may be employed to monitor the responsiveness of PVRL to treatment, which may influence decision making in the management of this disease.

4.
Anesthesiology ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31996550

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Patients with depression are more likely to develop chronic pain and vice versa.Neuroimaging studies reveal that many brain regions implicated in depression also contribute to central pain processing.The mechanisms through which depressive states influence pain processing are poorly understood. WHAT THIS ARTICLE TELLS US THAT IS NEW: Chemogenetic experiments in a mouse model of depression reveal the involvement of a neural circuitry between the central amygdala and the periaqueductal gray in nociception.In this mouse model, pathologically increased activity of inhibitory γ-aminobutyric acid-mediated neurons in the central amygdala will result in the inhibition of inhibitory γ-aminobutyric acid-mediated neurons in the periaqueductal gray. This, in turn, will lead to the activation of glutamatergic cells involved in periaqueductal gray-mediated nociception.These findings provide a framework for how the central amygdala-periaqueductal gray circuitry may play a role in coping with nociception in depressive states. BACKGROUND: The mechanisms underlying depression-associated pain remain poorly understood. Using a mouse model of depression, the authors hypothesized that the central amygdala-periaqueductal gray circuitry is involved in pathologic nociception associated with depressive states. METHODS: The authors used chronic restraint stress to create a mouse model of nociception with depressive-like behaviors. They then used retrograde tracing strategies to dissect the pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal gray. The authors performed optogenetic and chemogenetic experiments to manipulate the activity of this pathway to explore its roles for nociception. RESULTS: The authors found that γ-aminobutyric acid-mediated (GABAergic) neurons from the central amygdala project onto GABAergic neurons of the ventrolateral periaqueductal gray, which, in turn, locally innervate their adjacent glutamatergic neurons. After chronic restraint stress, male mice displayed reliable nociception (control, mean ± SD: 0.34 ± 0.11 g, n = 7 mice; chronic restraint stress, 0.18 ± 0.11 g, n = 9 mice, P = 0.011). Comparable nociception phenotypes were observed in female mice. After chronic restraint stress, increased circuit activity was generated by disinhibition of glutamatergic neurons of the ventrolateral periaqueductal gray by local GABAergic interneurons via receiving enhanced central amygdala GABAergic inputs. Inhibition of this circuit increased nociception in chronic restraint stress mice (median [25th, 75th percentiles]: 0.16 [0.16, 0.16] g to 0.07 [0.04, 0.16] g, n = 7 mice per group, P < 0.001). In contrast, activation of this pathway reduced nociception (mean ± SD: 0.16 ± 0.08 g to 0.34 ± 0.13 g, n = 7 mice per group, P < 0.001). CONCLUSIONS: These findings indicate that the central amygdala-ventrolateral periaqueductal gray pathway may mediate some aspects of pain symptoms under depression conditions.

5.
ACS Appl Mater Interfaces ; 12(5): 6268-6275, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31933362

RESUMO

Mercury ion (Hg2+), a bioaccumulating and toxic heavy metal, can cause severe damages to the environment and human health. Therefore, development of high-performance Hg2+ sensors is highly desirable. Herein, we construct a uniform dodecahedral shaped N-doped carbon decorated by single Fe site enzyme (Fe-N-C SAE), which exhibits good performance for Hg2+ detection. The N atom on Fe-N-C SAE can specifically recognize Hg2+ through chelation between Hg2+ and N atom, while the catalytic site on the single-atom enzyme acts as a signal amplifier. The Fe-N-C SAE-functionalized solution-gated graphene transistor exhibits a dramatic improvement in the selectivity and sensitivity of the devices. The sensor can rapidly detect Hg2+ down to 1 nM within 2 s. Besides, a relatively good repeatability and reproducibility for the detection of Hg2+ have also been found in our sensor platform. Our findings expand the application of single-atom catalysts in the field of food safety and environmental monitoring.

6.
Nat Commun ; 11(1): 570, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996679

RESUMO

Localization of the N-methyl-D-aspartate type glutamate receptor (NMDAR) to dendritic spines is essential for excitatory synaptic transmission and plasticity. Rather than remaining trapped at synaptic sites, NMDA receptors undergo constant cycling into and out of the postsynaptic density. Receptor movement is constrained by protein-protein interactions with both the intracellular and extracellular domains of the NMDAR. The role of extracellular interactions on the mobility of the NMDAR is poorly understood. Here we demonstrate that the positive surface charge of the hinge region of the N-terminal domain in the GluN1 subunit of the NMDAR is required to maintain NMDARs at dendritic spine synapses and mediates the direct extracellular interaction with a negatively charged phospho-tyrosine on the receptor tyrosine kinase EphB2. Loss of the EphB-NMDAR interaction by either mutating GluN1 or knocking down endogenous EphB2 increases NMDAR mobility. These findings begin to define a mechanism for extracellular interactions mediated by charged domains.

7.
Pain ; 161(2): 416-428, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31651582

RESUMO

Chronic pain and anxiety symptoms are frequently encountered clinically, but the neural circuit mechanisms underlying the comorbid anxiety symptoms in pain (CASP) in context of chronic pain remain unclear. Using viral neuronal tracing in mice, we identified a previously unknown pathway whereby glutamatergic neurons from layer 5 of the hindlimb primary somatosensory cortex (S1) (Glu), a well-known brain region involved in pain processing, project to GABAergic neurons in the caudal dorsolateral striatum (GABA). In a persistent inflammatory pain model induced by complete Freund's adjuvant injection, enhanced excitation of the Glu→GABA pathway was found in mice exhibiting CASP. Reversing this pathway using chemogenetic or optogenetic approaches alleviated CASP. In addition, the optical activation of Glu terminals in the cDLS produced anxiety-like behaviors in naive mice. Overall, the current study demonstrates the putative importance of a novel Glu→GABA pathway in controlling at least some aspects of CASP.

8.
Eur J Drug Metab Pharmacokinet ; 45(1): 15-26, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31494843

RESUMO

BACKGROUND: SPH3127 is a novel direct renin inhibitor designed as an oral drug for the regulation of blood pressure and body fluid homeostasis via the renin-angiotensin-aldosterone system (RAAS). This candidate is now being evaluated in a phase I clinical trial in China. OBJECTIVES: The purpose of this study is to investigate detailed nonclinical pharmacokinetic data, and to predict human pharmacokinetic parameters. METHODS: In vivo pharmacokinetic studies of SPH3127 were performed to investigate the exposure, absorption, clearance, distribution and metabolism after intravenous and oral administration in rats, beagle dogs and cynomolgus monkeys. The cynomolgus monkey pharmacokinetics/pharmacodynamics study was conducted to investigate the effect-concentration relationship of SPH3127. Its human pharmacokinetic properties were predicted employing an allometric scaling approach based on non-clinical species data. In vitro studies were also employed in a cytochrome P450 (CYP) enzyme phenotyping study, an inhibition and induction study, and a Caco-2 cell permeation and metabolites profile analysis. RESULTS: After a single intravenous administration of SPH3127 in rats and monkeys, high clearance and volume of distribution and a short terminal elimination half-life were seen for both species. The oral bioavailability of SPH3127 to rats and monkeys was about 11.5-24.5% and 3.3-11.3%, respectively, with the short peak time, Tmax, ranging from 0.25 to 1.3 h. SPH3127 shows low permeability across Caco-2 cell membranes, and as the substrate of p-gp with apparent efflux characteristics. SPH3127 is mainly distributed in the gastrointestine, liver, kidney, pancreas and lung after oral dose in rats, and which decreased quickly to a 1% peak concentration during 12 h. The plasma protein binding ratio of SPH3127 is low as 11.7-14.8% for all species. Excretion studies in rats suggested that fecal, urine and bile excretion represented about 15% of the intake dose, indicating that SPH3127 undergoes extensive metabolism after oral dosing. Phenotyping data revealed that CYP3A4 was the most active enzyme catalyzing the metabolism of SPH3127. The key metabolites were likely N-hydroxylation (M8-7), mono-oxidation-dehydrogenation (M7-4) and mono-oxidation (M8-1, M8-2), both for in vitro liver microsome incubation of all species and in vivo results in rats. The in vitro CYP inhibition study only found very weak action for CYP3A4 (midazolam 1'-hydroxylation) and CYP3A4 (midazolam 6ß-hydroxylation) with IC50 of 56.8 µM and 41.1 µM, respectively. Monkey pharmacokinetic/pharmacodynamic data showed favorable safety margins when compared with the exposure of the effect dose and that of the monkey NOAEL level. Simple four-species allometric scaling led to predicted human plasma clearance and volume of distribution, and then simulated the oral human plasma concentration-time profile, which are both in good consistency with phase I clinical trial pharmacokinetic data. CONCLUSIONS: SPH 3127 has appropriate pharmacokinetic properties for further clinical exploration.

9.
Int J Biol Macromol ; 144: 76-84, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31837366

RESUMO

This study was to investigate the potential prebiotic function of exopolysaccharide (EPS) from a medicinal fungus and the relationship to the molecular properties by in vitro human fecal fermentation. The EPS from Cordyceps sinensis Cs-HK1 mycelial fermentation was processed into three fractions with different monosaccharide contents, a higher molecular weight (MW) and a lower MW attained by two-step ethanol precipitation, and an intermediate MW by ultrasound-degradation of EPS. All the EPS fractions were well utilized during 24-48 h of fecal fermentation, leading to significant increases in the short chain fatty acid (SCFA) production. The consumption rate and production level of SCFAs varied slightly with the different EPS fractions. The EPS also influenced the composition and diversity of the fecal microflora, increasing the relative abundance of Firmicutes but suppressing that of Proteobacteria, which may be a beneficial effect for human health. Overall the results have shown that the Cs-HK1 EPS has significant prebiotic activity which is dependent on its molecular properties.

10.
J Nanosci Nanotechnol ; 20(3): 1670-1677, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492329

RESUMO

A series of Ag-Co-MCM-41 with different metal loadings have been synthesized through the hydrothermal method. All the prepared catalysts were characterized by N2 adsorption-desorption, X-ray diffraction analysis, transmission electron microscopy. The results revealed that the structure of MCM-41 was well preserved and Ag and Co have been introduced successfully into the mesoporous channels of MCM-41. The liquid-phase catalytic oxidation of styrene on these catalysts was investigated using H2O2 as an oxidizing agent and acetone as a solvent in thermostatic water bath. The influence of metal loading, the catalyst dose, temperature, time and styrene/oxidant molar ratio on the conversion of styrene and yield and selectivity of benzaldehyde was investigated. Also, the reusability of the catalysts was evaluated.

11.
Onco Targets Ther ; 12: 9077-9084, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31806992

RESUMO

Purpose: We aimed to establish a prediction model based on preoperative clinicopathologic features and intraoperative frozen section examination for precise prediction of metastatic involvement of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) in patients with papillary thyroid carcinoma (PTC). Methods: Clinicopathologic data pertaining to patients with PTC who underwent initial thyroid surgery between July 2015 and December 2017 were collected from electronic medical records. Multivariate logistic regression analysis was performed to identify independent predictors of LN-prRLN metastasis for incorporation in the nomogram. The performance of the model was assessed using discriminative ability, calibration, and clinical application. Results: A total of 592 patients were enrolled in this study. The LN-prRLN metastatic positivity was 19% (95% confidence interval [CI], 15.61-21.89%). On multivariate analysis, ultrasonography-reported LN status, extrathyroid extension, Delphian lymph node metastasis, and number of metastatic pretracheal and paratracheal lymph nodes were independent predictors of LN-prRLN metastasis. The nomogram showed good discriminative ability (C-index: 0.87; [95% CI, 0.84-0.91]; bias-corrected C-index: 0.86 [through bootstrapping validation]) and was well calibrated. The decision curve analysis indicated potential clinical usefulness of the nomogram. Conclusion: This study demonstrates that the risk of LN-prRLN metastasis in individual patients can be robustly predicted by a nomogram that integrates readily available preoperative clinicopathologic features and intraoperative frozen section examination. The nomogram may facilitate intraoperative decision-making for patients with PTC.

12.
Cell Rep ; 29(12): 3847-3858.e5, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31851918

RESUMO

While comorbid pain in depression (CP) occurs at a high rate worldwide, the neural connections underlying the core symptoms of CP have yet to be elucidated. Here, we define a pathway whereby GABAergic neurons from the central nucleus of the amygdala (GABACeA) project to glutamatergic neurons in the parafascicular nucleus (GluPF). These GluPF neurons relay directly to neurons in the second somatosensory cortex (S2), a well-known area involved in pain signal processing. Enhanced inhibition of the GABACeA→GluPF→S2 pathway is found in mice exhibiting CP symptoms. Reversing this pathway using chemogenetic or optogenetic approaches alleviates CP symptoms. Together, the current study demonstrates the putative importance of the GABACeA→GluPF→S2 pathway in controlling at least some aspects of CP.

13.
J Burn Care Res ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31872859

RESUMO

An overall assessment of the diagnostic value of laser Doppler imaging (LDI) to assess burn depth in patients is presented based on relevant studies. Both eligible research and relevant articles were identified through specific index searches of Embase, Cochrane and PubMed databases. The latest study included was published in March 2019 and all eligible publications reported on cohort or cross-sectional research. All articles were tested for heterogeneity by using a suitable effect model to calculate amalgamative values of sensitivity, specificity and the diagnostic odds ratio (DOR). Analyses of summary receiver operating characteristic (SROC) are given for burn depth values. After rigorous screening, 14 studies with a total cohort of 1,818 patients were chosen for the meta-analysis to explore the validity of LDI diagnosis to assess the depth of burns. The burn depth overall sensitivity for LDI was 91% (95% CI: 86-95%) and global specificity was 96% (95% CI: 92-98%). The overall positive likelihood ratio of LDI was 20.35 (95% CI: 10.71-38.69) and the overall negative likelihood ratio was 0.09 (95% CI: 0.05-0.15). The overall DOR was 152.93 (95% CI: 69.44-336.81) of LDI. The acreage under the SROC was not low for LDI (AUC = 0.98; 95% CI: 0.96-0.99). In conclusion, the present analysis reviewed the literature and meta-analysis of studies to validate LDI for the diagnosis of burn depth. The results indicated that LDI has a high accuracy for this diagnostic function.

14.
Mol Oncol ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782885

RESUMO

Identification of new genetic pathways or molecular targets that sensitize cancer cells to chemotherapeutic drugs may improve the efficacy of current chemotherapy. Here, we report that downmodulation of UHRF1 (ubiquitin-like with PHD and RING finger domains 1) in retinoblastoma (RB) cells increases the sensitivity to histone deacetylase (HDAC) inhibitors, augmenting apoptotic cell death. We found that UHRF1 depletion downregulates two redox-responsive genes GSTA4 (glutathione S-transferase α4) and TXN2 (thioredoxin-2) in RB cells, and increases the basal level of intracellular oxidative stress. Antioxidant treatment significantly reduced both basal and HDAC inhibitor-induced DNA damage and apoptosis in UHRF1-depleted cells. Knockdown of GSTA4 or TXN2 sensitized RB cells to HDAC inhibitors, demonstrating that GSTA4 and TXN2 play key roles in redox homeostasis in RB cells and the susceptibility to HDAC inhibitor treatment upon UHRF1 depletion. In human primary RB, GSTA4 and TXN2 proteins were found to be mostly elevated along with high UHRF1 expression. In addition to augmentation of apoptosis in UHRF1-depleted RB cells, we also show that UHRF1 downmodulation derepresses the expression of photoreceptor-specific genes in RB cells in cooperation with a HDAC inhibitor MS-275 and promotes neuron-like differentiation. However, further investigation revealed that the enhanced growth-inhibitory effects of MS-275 in UHRF1-depleted cells were still mainly due to robust apoptosis induction rather than differentiation-mediated growth arrest. Consistent with our findings, UHRF1 depletion in RB cells increased the therapeutic efficacy of MS-275 in murine orthotopic xenografts. These results provide a novel basis for potential benefits of UHRF1 targeting for RB treatment.

15.
Membranes (Basel) ; 9(12)2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771228

RESUMO

ZnO was deposited on macroporous α-alumina membranes via atomic layer deposition (ALD) to improve water flux by increasing their hydrophilicity and reducing mass transfer resistance through membrane pore channels. The deposition of ZnO was systemically performed for 4-128 cycles of ALD at 170 °C. Analysis of membrane surface by contact angles (CA) measurements revealed that the hydrophilicity of the ZnO ALD membrane was enhanced with increasing the number of ALD cycles. It was observed that a vacuum-assisted 'flow-through' evaporation method had significantly higher efficacy in comparison to conventional desalination methods. By using the vacuum-assisted 'flow-through' technique, the water flux of the ZnO ALD membrane (~170 L m-2 h-1) was obtained, which is higher than uncoated pristine membranes (92 L m-2 h-1). It was also found that ZnO ALD membranes substantially improved water flux while keeping excellent salt rejection rate (>99.9%). Ultrasonic membrane cleaning had considerable effect on reducing the membrane fouling.

16.
Invest Ophthalmol Vis Sci ; 60(14): 4858-4864, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747686

RESUMO

Purpose: We investigate temporal synchrony within one eye and between both eyes in adults with amblyopia. Methods: Eight adult amblyopes (range, 19.88-27.81 years old; median, 22.86 years old) and 12 age-matched adults with normal vision (range, 21.2-50.30 years old; median, 23.78 years old) participated in the experiment. We showed two pairs of Gaussian blobs flickering at 1 Hz as visual stimuli, one pair with the same temporal phase modulation (i.e., the reference) and another pair with a distinct temporal phase (i.e., the signal). We employed the constant stimuli method to measure the minimum degree of temporal phase (temporal synchrony threshold), at which participants were able to discriminate the signal pair under binocular, monocular, and dichoptic viewing configurations. Results: The temporal synchrony threshold was different across the six configurations (P = 0.001). There was also an interaction between the configuration and the group (P = 0.004). The synchrony threshold was significantly higher in amblyopes than in controls under the configurations where two pairs of blobs were presented to the amblyopic eye (136.52 ± 50.19 vs. 97.08 ± 22.02 ms, P = 0.027) and where the paired blobs were presented to different eyes (163.15 ± 80.85 vs. 111.61 ± 22.46 ms, P = 0.049). The visual deficits in these two configurations were significantly correlated (r = 0.824, P = 0.012). Conclusions: The threshold for detecting temporal asynchrony increased when the stimuli were presented only to the amblyopic eye and when they were dichoptically presented to the amblyopic and fellow eyes.


Assuntos
Ambliopia/fisiopatologia , Transtornos da Percepção/fisiopatologia , Limiar Sensorial/fisiologia , Visão Binocular/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/fisiologia , Percepção Espacial/fisiologia , Análise Espaço-Temporal , Visão Monocular/fisiologia , Acuidade Visual/fisiologia , Adulto Jovem
17.
Biomed Res Int ; 2019: 8270187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687400

RESUMO

Purpose: To detect the responsiveness and predictive ability of the Chinese version Action Research Arm Test (C-ARAT) in participants within the first 3 months after cerebral infarction. Methods: Ninety-seven individuals (75 men, mean age 59.87 ± 10.94 years) with a first cerebral infarction were enrolled in this study. The participants were evaluated by two outcome measures: C-ARAT and the Barthel Activities of Daily Living Index (BI) at five time points: 0D, 3W, 3M, 6M and 1Y after enrolment. The standardised response mean (SRM) and the Wilcoxon signed rank test were used to analyse responsiveness. Predictive validity was determined by using Spearman's rank correlation coefficients. The predicted performance of C-ARAT on activities of daily living (ADLs) was measured by linear regression model. Floor and ceiling effects were estimated by counting the proportion of subjects falling outside the 5% lower or upper boundary, respectively. Results: The C-ARAT showed moderate to large responsiveness in detecting changes over time (SRM = 0.58-0.84). The C-ARAT subscales showed small to large responsiveness (SRM = 0.44-0.90). The C-ARAT at 0D showed moderate to good correlation with the BI scores at 3W, 3M and 6M (ρ = 0.561-0.624, p < 0.001), and exhibited fair correlation with the BI score 1Y after enrolment (ρ = 0.384, p < 0.05). C-ARAT was a good predictor (adjusted R 2 = 0.185-0.249) of BI within 3M follow-up. The C-ARAT total score showed a notable floor effect at 0D and 3W and a notable ceiling effect at 3M, 6M and 1Y. Conclusion: The results of this study support the use of the C-ARAT as a measurement of upper extremity function in individuals with a first cerebral infarction.

18.
Dalton Trans ; 48(46): 17169-17173, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31720614

RESUMO

A magnetic internal heating single-precursor approach was exploited to fabricate higher quality Prussian blue nanoparticles (PBNPs) with excellent crystallinity, dispersibility and uniformity. Furthermore, the magnetic properties and MRI contrast effect were improved. Subsequently, significantly increased nanoenzyme activity has been demonstrated.

19.
FEBS J ; 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31736227

RESUMO

Endoplasmic reticulum (ER) stress and autophagy dysfunction contribute to the establishment and progression of diverse pathologies. Proteolytic activation of the transcription factor nSREBP1 is induced under ER stress; however, little is known about how SREBP1 and its nuclear active form nSREBP1 influence autophagy and unfolded protein response (UPR) activation in osteosarcoma cells. Our research focused on the effect of SREBP1/nSREBP1 upon apoptosis and autophagy during ER stress and the molecular mechanisms involved. Here, we showed that nSREBP1 binds to the promoter of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and then regulates ER stress, cell growth, cell apoptosis, and autophagy through the PERK signaling pathway. nSREBP1 increased PERK gene expression and phosphorylation. nSREBP1 was further demonstrated to activate ER stress response through stimulatory effects on PERK signaling. Overexpression of SREBP1 increased its cleavage and release of nSREBP1; therefore, the effect of SREBP1 is achieved through the enhancement of the expression of nSREBP1. Overexpression of SREBP1/nSREBP1 amplifies PERK-associated cell cycle stagnation with G1 phase arresting, S phase reducing, and G2-M phase delaying. LV-SREBP1/nSREBP1 can also bolster PERK's ER stress-associated pro-apoptotic effects. LV-SREBP1/nSREBP1 and LV-PERK can activate autophagy in ER stress response, along with the overexpression of SREBP1/nSREBP1 and PERK. This resulted in amplification of PERK-related changes to cell proliferation and ER stress-mediated apoptosis and autophagy, with the biological effect of nSREBP1 relying on PERK, which makes up one of the three branches of the UPR signaling pathway. This study reveals important roles for SREBP1/nSREBP1 in PERK signaling under ER stress. Furthermore, nSREBP1, the nuclear active form of SREBP1, is able to robustly augment the effects of PERK. Description of the link between PERK and SREBP1/nSREBP1 function offers an improved understanding of the ER stress response and insight into the biological function of SREBP1/nSREBP1.

20.
Commun Biol ; 2: 410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754640

RESUMO

Bacterial ClpP is a highly conserved, cylindrical, self-compartmentalizing serine protease required for maintaining cellular proteostasis. Small molecule acyldepsipeptides (ADEPs) and activators of self-compartmentalized proteases 1 (ACP1s) cause dysregulation and activation of ClpP, leading to bacterial cell death, highlighting their potential use as novel antibiotics. Structural changes in Neisseria meningitidis and Escherichia coli ClpP upon binding to novel ACP1 and ADEP analogs were probed by X-ray crystallography, methyl-TROSY NMR, and small angle X-ray scattering. ACP1 and ADEP induce distinct conformational changes in the ClpP structure. However, reorganization of electrostatic interaction networks at the ClpP entrance pores is necessary and sufficient for activation. Further activation is achieved by formation of ordered N-terminal axial loops and reduction in the structural heterogeneity of the ClpP cylinder. Activating mutations recapitulate the structural effects of small molecule activator binding. Our data, together with previous findings, provide a structural basis for a unified mechanism of compound-based ClpP activation.

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