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1.
Neurotherapeutics ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33447904

RESUMO

During intracranial aneurysm embolization with the Pipeline embolization device (PED), ischemic and hemorrhagic complications have been observed in cases among Western populations. The postmarket multicenter registry study on the embolization of intracranial aneurysms with the PED in China, i.e., the PLUS study, was performed to assess real-world predictors of complications and functional outcomes in patients treated with the PED in a Chinese population. All patients with intracranial aneurysms who underwent embolization using the PED between November 2014 and October 2019 across 14 centers in China were included. The study endpoints included preoperative and early postoperative (< 30 days) functional outcomes (modified Rankin scale [mRS] scores) and complications related to PED treatment at early postoperative and follow-up time points (3-36 months). Multivariate analysis was performed to identify risk factors for complications. A total of 1171 consecutive patients (mean age, 53.9 ± 11.4; female, 69.6% [813/1171]) with 1322 aneurysms were included in the study. Hypertension, basilar artery aneurysms, and successful deployment after adjustment or unsuccessful device deployment were found to be independent predictors of ischemic stroke, while the use of the Flex PED and incomplete occlusion immediately after treatment were protective factors. An aneurysm size > 10 mm, distal anterior circulation aneurysms, and adjunctive coiling were found to be independent predictors of delayed aneurysm rupture, distal intraparenchymal hemorrhage, and neurological compression symptoms, respectively. The rate of PED-related complications in the PLUS study was similar to that in Western populations. The PLUS study identified successful deployment after adjustment or unsuccessful device deployment and the degree of immediate postoperative occlusion as novel independent predictors of PED-related ischemic stroke in a Chinese population. ClinicalTrial.gov Identifier: NCT03831672.

2.
Med Sci Monit ; 27: e928108, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33446627

RESUMO

Most reported neurological symptoms that happen after exposure to microgravity could be originated from alterations in cerebral hemodynamics. The complicated mechanisms involved in the process of hemodynamics and the disparate experimental protocols designed to study the process may have contributed to the discrepancies in results between studies and the lack of consensus among researchers. This literature review examines spaceflight and ground-based studies of cerebral hemodynamics and aims to summarize the underlying physiological mechanisms that are altered in cerebral hemodynamics during microgravity. We reviewed studies that were published before July 2020 and sought to provide a comprehensive summary of the physiological or pathological theories of hemodynamics and to arrive at firm conclusions from incongruous results that were reported in those related articles. We give plausible explanations of inconsistent results on factors including intracranial pressure, cerebral blood flow, and cerebrovascular autoregulation. Although there are no definitive data to confirm how cerebral hemodynamics changes during microgravity, every discrepancy in results was interpreted by existing theories, which were derived from physiological and pathological processes. We conclude that microgravity-induced alterations of hemodynamics at the brain level are multifaceted. Factors including duration, partial pressures of carbon dioxide, and individual adaptability contribute to this process and are unpredictable. With a growing understanding of this hemodynamics model, additional factors will likely be considered. Aiming for a full understanding of the physiological and/or pathological changes of hemodynamics will enable researchers to investigate its cellular and molecular mechanisms in future studies, which are desperately needed.

3.
J Hazard Mater ; 402: 123445, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33254733

RESUMO

In this work, we decorated gold nanoparticles (Au NPs) in the porous, three-dimensional sugarcane membrane for the flow catalytical and antibacterial application. Due to the uniformly distributed Au NPs in sugarcane channels and the porous structure of sugarcane, the interaction between contaminant and catalysis was enhanced as water flowing through the Au NPs/sugarcane membrane. The Au NPs/sugarcane membrane exhibited superior catalytical efficiency for removing methylene blue (MB) with a turn over frequency of 0.27 molMB·molAu-1·min-1 and the water treatment rate reached up to 1.15×105 L/m2 h with >98.3 % MB removal efficiency. The Au NPs/sugarcane membrane also exhibited superior bacterial removal efficiency as E. coli suspension flowing through it, due to the superimposition effects of physical barrier in sugarcane and the antibacterial property of Au NPs. The tremendous catalytical and antibacterial performance of Au NPs/sugarcane membrane provides a promising potential for the rational design of flow catalytical membrane reactor to purify the microbial contaminated water.

4.
Ecotoxicol Environ Saf ; 207: 111306, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949934

RESUMO

Although studies have demonstrated that fine particulate matter (PM2.5) induces ocular surface damage, PM2.5 exposure causes cornea toxicity is not entirely clear. The aim of this study is to investigate the role of the nod-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis in PM2.5-related corneal toxicity. Human corneal epithelial cells (HCECs) were exposed to different concentrations of PM2.5, and the cell viability, expressions of NLRP3 inflammasome mediated pyroptosis axis molecules and intracellular reactive oxygen species (ROS) formation were measured in HCECs. Animal experiments were undertaken to topically apply PM2.5 suspension to mouse eyes for three months and the pyroptosis related molecules in the mouse corneas were measured. RESULTS: Our results showed a dose-dependent decrease of HCEC viability in the PM2.5-treated cells. NLRP3 inflammasome-mediated pyroptosis axis (NLRP3, ASC, GSDMD, caspase-1, IL-1ß, and IL-18) were activated in the PM2.5-treated HCECs, accompanied by increased ROS formation. Further in vivo study confirmed the activation of this pathway in the mouse corneas exposed to PM2.5. In conclusion, this study provids novel evidence that PM2.5 induces corneal toxicity by triggering cell pyroptosis.


Assuntos
Córnea/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Material Particulado/toxicidade , Piroptose/efeitos dos fármacos , Animais , Caspase 1/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Córnea/patologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Inflamação , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo
5.
Forensic Sci Int ; 318: 110637, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33309992

RESUMO

Sudden cardiac death (SCD) has become a global problem due to its high mortality in the general population. Identification of genetic factors predisposed to SCD is significant since it enables genetic testing that would contribute to molecular diagnosis and risk stratification of SCD. It has been reported that HSPA1B gene mutations might be related with SCD. In this study, based on candidate-gene-based approach and systematic screening strategy, a 5-base pair insertion/deletion (Indel) polymorphism (rs3036297) in the 3'UTR of HSPA1B gene was selected to perform a case-control study aiming to investigate its association with SCD susceptibility in Chinese populations. Logistic regression analysis showed that the insertion allele of rs3036297 was correlated with a comparatively lower risk for SCD [OR=0.58, 95%CI=0.43-0.77, P=1.28×10-4] compared with the deletion allele. Luciferase activity assay indicated that HSPA1B expression could be regulated by rs3036297 through interfering binding with miR-134-5p. Furthermore, analysis of database from Haploreg and GTEx revealed that the rs3036297 variant was involved in potential cis-regulatory element with the promoter of HLA-DRB5 through a long-range interaction and the deletion allele of rs3036297 increased HLA-DRB5 expression. In conclusion, the rs3036297 variant may regulate HSPA1B expression via a mechanism of miRNA binding and HLA-DRB5 expression via a long-range promoter interaction through which contributed to SCD susceptibility. Therefore, rs3036297 would be a potential marker for molecular diagnosis and genetic counseling of SCD.

6.
Cell Biosci ; 10(1): 135, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33292473

RESUMO

BACKGROUND: Epilepsy is characterized by the typical symptom of seizure, and anti-seizure medications are the main therapeutic method in clinical, but the effects of these therapy have not been satisfactory. To find a better treatment, it makes sense to further explore the regulatory mechanisms of seizures at genetic level. Lrp4 regionally expresses in mice hippocampus where is key to limbic epileptogenesis. It is well known that neurons release a high level of glutamate during seizures, and it has been reported that Lrp4 in astrocytes down-regulates glutamate released from neurons. However, it is still unclear whether there is a relationship between Lrp4 expression level and seizures, and whether Lrp4 plays a role in seizures. RESULTS: We found that seizures induced by pilocarpine decreased Lrp4 expression level and increased miR-351-5p expression level in mice hippocampus. Glutamate reduced Lrp4 expression and enhanced miR-351-5p expression in cultured hippocampal astrocytes, and these effects can be partially attenuated by AP5. Furthermore, miR-351-5p inhibitor lessened the reduction of Lrp4 expression in glutamate treated hippocampal astrocytes. Local reduction of Lrp4 in hippocampus by sh Lrp4 lentivirus injection in hippocampus increased the threshold of seizures in pilocarpine or pentylenetetrazol (PTZ) injected mice. CONCLUSIONS: These results indicated that high released glutamate induced by seizures down-regulated astrocytic Lrp4 through increasing miR-351-5p in hippocampal astrocytes via activating astrocytic NMDA receptor, and locally reduction of Lrp4 in hippocampus increased the threshold of seizures. Lrp4 in hippocampal astrocytes appears to serve as a negative feedback factor in seizures. This provides a new potential therapeutic target for seizures regulation.

7.
Environ Res ; : 110596, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33307083

RESUMO

With the global lockdown, meteorological factors are highly discussed for COVID-19 transmission. In this study, national-specific and region-specific data sets from Germany, Italy, Spain and the United Kingdom were used to explore the effect of temperature, absolute humidity and diurnal temperature range (DTR) on COVID-19 transmission. From February 1st to November 1st, a 7-day COVID-19 case doubling time (Td), meteorological factors with cumulative 14-day-lagged, government response index and other factors were fitted in the distributed lag nonlinear models. The overall relative risk (RR) of the 10th and the 25th percentiles temperature compared to the median were 0.0074 (95% CI: 0.0023, 0.0237) and 0.1220 (95% CI: 0.0667, 0.2232), respectively. The pooled RR of lower (10th, 25th) and extremely high (90th) absolute humidity were 0.3266 (95% CI: 0.1379, 0.7734), 0.6018 (95% CI: 0.4693, 0.7718) and 0.3438 (95% CI: 0.2254, 0.5242), respectively. While the DTR did not have a significant effect on Td. The total cumulative effect of temperature (10th) and absolute humidity (10th, 90th) on Td increased with the change of lag days. Similarly, a decline in temperature and absolute humidity at cumulative 14-day-lagged corresponded to the lower RR on Td in pooled region-specific effects. In summary, the government responses are important factors in alleviating the spread of COVID-19. After controlling that, our results indicate that both the cold and the dry environment also likely facilitate the COVID-19 transmission.

9.
Curr Mol Med ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272176

RESUMO

Male fertility is closely related to the normal function of the hypothalamic-pituitary-testicular axis. The testis is an important male reproductive organ that secretes androgen and produces sperm through spermatogenesis. Spermatogenesis refers to the process by which spermatogonial stem cells (SSCs) produce highly differentiated spermatozoa and is divided into three stages: mitosis, meiosis and spermiogenesis. Spermatogenesis requires SSCs to strike a proper balance between self-renewal and differentiation and the commitment of spermatocytes to meiosis, which involves many molecules and signalling pathways. Abnormal gene expression or signal transduction in the hypothalamus and pituitary, but particularly in the testis, may lead to spermatogenic disorders and male infertility. The phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in many stages of male reproduction, including the regulation of the hypothalamus-pituitary-gonad (HPG) axis during spermatogenesis, the proliferation and differentiation of spermatogonia and somatic cells, and the regulation of sperm autophagy and testicular endocrine function in the presence of environmental pollutants, particularly endocrine-disrupting chemicals (EDCs). In the PI3K/AKT/mTOR signalling pathway, mTOR is considered the central integrator of several signals, regulating metabolism, cell growth and proliferation. In particular, mTOR plays an important role in the maintenance and differentiation of SSCs, as well as in regulating the redox balance and metabolic activity of Sertoli cells, which play an important role in nutritional support during spermatogenesis.

11.
Ther Adv Neurol Disord ; 13: 1756286420967828, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224273

RESUMO

Background and Purpose: The Pipeline Embolization Device (PED, Covidien/Medtronic) is widely used to treat intracranial aneurysms. This PED in China post-market multi-center registry study (PLUS) investigated safety and effectiveness of the PED for intracranial aneurysms in the Chinese population. Methods: This was a panoramic, consecutive, real-world cohort registry study. Patients treated with PED with or without coils between November 2014 and October 2019 at 14 centers in China were included, and those treated by parent vessel occlusion or other stents were excluded. Study outcomes included angiographic evaluation of aneurysm occlusion, complications, in-stent stenosis, and predictors of aneurysm occlusion. A central committee reviewed all imaging and endpoint events. Results: In total, 1171 patients with 1322 intracranial aneurysms were included. The total occlusion rate was 81.4% (787/967) at mean follow-up of 8.96 ± 7.50 months, with 77.1% (380/493) occlusion in the PED alone and 85.9% (407/474) in the PED plus coiling group. On multi-variate analysis, female sex, hyperlipidemia, vertebral aneurysms, PED plus coiling, and blood flow detained to venous phase were significant predictors of aneurysm occlusion. In posterior circulation cohort, there was no variable associated with aneurysm occlusion. In-stent stenosis predictors included current smoking and cerebral sclerosis/stenosis. Conclusion: In the largest series on PED of multi-center date of China, data suggest that treatment with the flow-diverting PED in intracranial aneurysms was efficacious. The treatment of PED combined coiling and blood flow detained to venous phase after PED implant were associated with aneurysmal occlusion. The occlusion rate of vertebral aneurysms was higher than other location aneurysms. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03831672.

12.
DNA Cell Biol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33180568

RESUMO

Identifying common genetic variations that are related to sudden cardiac death (SCD) is crucial since it can facilitate the diagnosis and risk stratification of SCD. It has been reported that COX10 mutations might be related with SCD. In this study, we performed a systematic variant screening on the COX10 to filter potential functional genetic variations. Based on the screening results, an insertion/deletion polymorphism (rs397763766) in 3'untranslated regions of COX10 was selected as the candidate variant. We conducted a case-control study to investigate the association between rs397763766 and SCD susceptibility in Chinese populations. Logistic regression analysis showed that the deletion allele of rs397763766 was associated with an increased risk for SCD (odds ratio = 1.61, 95% confidence interval = 1.25-2.07, p = 1.87 × 10-4) susceptibility than insertion allele. Further genotype-phenotype analysis using human cardiac tissue samples suggested that COX10 expression level in genotypes containing deletion allele was higher than that in ins/ins genotype. The results were further reinforced by RNA sequencing data from 1000 Genomes Project. Luciferase activity assay indicated that COX10 expression could be regulated by rs397763766 through interfering binding with miR-15b, thus conferring risk of SCD. In conclusion, the novel rs397763766 polymorphism might be a potential marker for molecular diagnosis and genetic counseling of SCD.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 247: 119083, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33137629

RESUMO

Echinococcosis is a zoonotic parasitic disease transmitted by animals and distributed all over the world. There is no standardized and widely accepted treatment method, and early and accurate diagnosis is crucial for the prevention and cure of echinococcosis. Here, we explored the feasibility of using derivative Raman in combination with autofluorescence (AF) to improve the diagnosis performance of echinococcosis. The spectra of serum samples from patients with echinococcosis, as well as healthy volunteers, were recorded at 633 nm excitation. The normalized mean Raman spectra showed that there is a decrease in the relative amounts of ß carotene and phenylalanine and an increase in the percentage of tryptophan, tyrosine, and glutamic acid contents in the serum of echinococcosis patients as compared to that of healthy subjects. Then, principal components analysis (PCA), combined with linear discriminant analysis (LDA), were adopted to distinguish echinococcosis patients from healthy volunteers. Based on the area under the ROC curve (AUC) value, the derivative Raman + AF spectral data set achieved the optimal results. The AUC value was improved by 0.08 for derivative Raman + AF (AUC = 0.98), compared to Raman alone. The results demonstrated that the fusion of derivative Raman and AF could effectively improve the performance of the diagnostic model, and this technique has great application potential in the clinical screening of echinococcosis.

14.
Artigo em Chinês | MEDLINE | ID: mdl-33254313

RESUMO

Objective:The etiology and pathophysiologic mechanism of sudden sensorineural hearing loss are undefined. We will use artificial intelligence and big data methods to explore the correlation between sudden sensorineural hearing loss and serum indices. Method:A total of 1218 patients with sudden deafness admitted to Sun Yat-sen Memorial Hospital were selected as the experimental group, 95 861 healthy subjects were randomly selected as the control group at the same period. Serum biochemical indexes in two groups were collected and analyzed by TreeNet and CART machine learning algorithms, to screen out highly correlated indicators with sudden sensorineural hearing loss and dig out a set of clinical features for people with high risk of sudden sensorineural hearing loss. Result:It was found that high prevalence rate of sudden sensorineural hearing loss is related to eosinophils, reticulocyte and fibrinogen. The areas under the receiver operator characteristic curves(ROC-AUC) were exploited to evaluate the prediction performance of TreeNet model. Overall the TreeNet model has provided high predictive ability by ROC curve, achieving AUC of 0.99, both recall and accuracy rate of 99.90%. Conclusion:There is significant difference between sudden deadness and normal people in serum biochemical indexes. Eosinophil is the first important indicator to distinguish sudden sensorineural hearing loss. Treenet model has important referenced significance for the screening and diagnosis of sudden sensorineural hearing loss.

15.
Cell Death Dis ; 11(11): 971, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184264

RESUMO

Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS' role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/ß-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/ß-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.

16.
Opt Lett ; 45(19): 5356-5359, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001911

RESUMO

When the spatial frequencies of the object are insufficiently sampled, the reconstruction of ghost imaging will suffer from repetitive visual artifacts, which cannot be effectively tackled by existing ghost imaging reconstruction techniques. In this Letter, extensions of the CLEAN algorithm applied in ghost imaging are explored to eliminate those artifacts. Combined with the point spread function estimation using the second-order coherence measurement in ghost imaging, our modified CLEAN algorithm is demonstrated to have a fast and noteworthy improvement against the spatial-frequency insufficiency, even for the extreme sparse sampling cases. A brief explanation of the algorithm and performance analysis are given.

17.
Brain Sci ; 10(10)2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33020379

RESUMO

Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 µM and 10 µM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.

18.
BMC Public Health ; 20(1): 1585, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087097

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, which has caused numerous deaths and health problems worldwide. This study aims to examine the effects of airborne particulate matter (PM) pollution and population mobility on COVID-19 across China. METHODS: We obtained daily confirmed cases of COVID-19, air particulate matter (PM2.5, PM10), weather parameters such as ambient temperature (AT) and absolute humidity (AH), and population mobility scale index (MSI) in 63 cities of China on a daily basis (excluding Wuhan) from January 01 to March 02, 2020. Then, the Generalized additive models (GAM) with a quasi-Poisson distribution were fitted to estimate the effects of PM10, PM2.5 and MSI on daily confirmed COVID-19 cases. RESULTS: We found each 1 unit increase in daily MSI was significantly positively associated with daily confirmed cases of COVID-19 in all lag days and the strongest estimated RR (1.21, 95% CIs:1.14 ~ 1.28) was observed at lag 014. In PM analysis, we found each 10 µg/m3 increase in the concentration of PM10 and PM2.5 was positively associated with the confirmed cases of COVID-19, and the estimated strongest RRs (both at lag 7) were 1.05 (95% CIs: 1.04, 1.07) and 1.06 (95% CIs: 1.04, 1.07), respectively. A similar trend was also found in all cumulative lag periods (from lag 01 to lag 014). The strongest effects for both PM10 and PM2.5 were at lag 014, and the RRs of each 10 µg/m3 increase were 1.18 (95% CIs:1.14, 1.22) and 1.23 (95% CIs:1.18, 1.29), respectively. CONCLUSIONS: Population mobility and airborne particulate matter may be associated with an increased risk of COVID-19 transmission.


Assuntos
Infecções por Coronavirus/epidemiologia , Material Particulado/efeitos adversos , Pneumonia Viral/epidemiologia , Dinâmica Populacional/estatística & dados numéricos , China/epidemiologia , Cidades/epidemiologia , Humanos , Pandemias , Material Particulado/análise , Medição de Risco
19.
Proc Natl Acad Sci U S A ; 117(42): 26448-26459, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33020269

RESUMO

Wnt signaling plays a critical role in production and differentiation of neurons and undergoes a progressive reduction during cortical development. However, how Wnt signaling is regulated is not well understood. Here we provide evidence for an indispensable role of neddylation, a ubiquitylation-like protein modification, in inhibiting Wnt/ß-catenin signaling. We show that ß-catenin is neddylated; and inhibiting ß-catenin neddylation increases its nuclear accumulation and Wnt/ß-catenin signaling. To test this hypothesis in vivo, we mutated Nae1, an obligative subunit of the E1 for neddylation in cortical progenitors. The mutation leads to eventual reduction in radial glia progenitors (RGPs). Consequently, the production of intermediate progenitors (IPs) and neurons is reduced, and neuron migration is impaired, resulting in disorganization of the cerebral cortex. These phenotypes are similar to those of ß-catenin gain-of-function mice. Finally, suppressing ß-catenin expression is able to rescue deficits of Nae1 mutant mice. Together, these observations identified a mechanism to regulate Wnt/ß-catenin signaling in cortical development.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33052668

RESUMO

Silicon (Si) has been considered as one of the most promising candidates for the next-generation lithium-ion battery (LIB) anode materials owing to its huge theoretical specific capacity of 4200 mA h g-1. However, the practical application of Si anodes in commercial LIBs is facing challenges because of the lack of scalable and cost-effective methods to prepare Si-based anode materials with proper microstructure and competitive electrochemical performances. Herein, we report a facile and scalable method to produce multidimensional porous silicon embedded with a nanosilver particle (pSi/Ag) composite from commercially available low-cost metallurgical-grade silicon (MG-Si) powder. The unique hybrid structure contributes to fast electronic transport and relieves volume change of silicon during the charge-discharge process. The pSi/Ag composite exhibits a large initial discharge capacity (3095 mA h g-1 at a high current of 1 A g-1), an excellent cycling performance (1930 mA h g-1 at 1 A g-1 after 50 cycles), and outstanding rate capacities (up to 1778 mA h g-1 at a higher current of 2 A g-1). After the samples are modified by reduced graphene oxide, the capacities of the pSi/Ag@RGO composite electrode can still be maintained over 1000 mA h g-1 after 200 cycles. This study provides a simple and effective strategy for production of high-performance anode materials.

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