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1.
Neurosci Bull ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052547

RESUMO

The ventral part of the anteromedial thalamic nucleus (AMv) is in a position to convey information to the cortico-hippocampal-amygdalar circuit involved in the processing of fear memory. Corticotropin-releasing-factor (CRF) neurons are closely associated with the regulation of stress and fear. However, few studies have focused on the role of thalamic CRF neurons in fear memory. In the present study, using a conditioned fear paradigm in CRF transgenic mice, we found that the c-Fos protein in the AMv CRF neurons was significantly increased after cued fear expression. Chemogenetic activation of AMv CRF neurons enhanced cued fear expression, whereas inhibition had the opposite effect on the cued fear response. Moreover, chemogenetic manipulation of AMv CRF neurons did not affect fear acquisition or contextual fear expression. In addition, anterograde tracing of projections revealed that AMv CRF neurons project to wide areas of the cerebral cortex and the limbic system. These results uncover a critical role of AMv CRF neurons in the regulation of conditioned fear memory.

2.
Sensors (Basel) ; 20(20)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053827

RESUMO

This work presents a fall detection system that is worn on the head, where the acceleration and posture are stable such that everyday movement can be identified without disturbing the wearer. Falling movements are recognized by comparing the acceleration and orientation of a wearer's head using prespecified thresholds. The proposed system consists of a triaxial accelerometer, gyroscope, and magnetometer; as such, a Madgwick's filter is adopted to improve the accuracy of the estimation of orientation. Moreover, with its integrated Wi-Fi module, the proposed system can notify an emergency contact in a timely manner to provide help for the falling person. Based on experimental results concerning falling movements and activities of daily living, the proposed system achieved a sensitivity of 96.67% in fall detection, with a specificity of 98.27%, and, therefore, is suitable for detecting falling movements in daily life.

3.
Biol Pharm Bull ; 43(10): 1481-1489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999158

RESUMO

Stroke is a common cerebrovascular disease. Inflammation-induced neuronal death is one of the key factors in stroke pathology. Propofol has been shown to ameliorate neuroinflammatory injury, but the exact mechanism of its neuroprotective role remains to be fully elucidated. In the present study, we found that inflammation was activated in ischemic cortical neurons, and the expression of nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 1 (NLRP1), NLRP3 inflammasome and effectors in primary cortical neurons increased. However, we found that propofol could inhibit the increased expression of NLRP1 and NLRP3 inflammasome induced by oxygen-glucose deprivation (OGD). Furthermore, the effector molecule caspase-1 (casp1) was revealed to be the downstream target of NLRP1 and propofol repressed the activation of caspase-1 via inhibiting NLRP1 in cortical neurons. Moreover, propofol inhibits caspase-6 activation in neurons through the NLRP1-caspase-1 pathway. Once the expression of caspase6 increases, propofol reduced its neuroprotective effect in OGD-treated cortical neurons. In the stroke middle cerebral artery occlusion (MCAO) model, infusion of caspase-6 inhibitors enhanced the protective effect of propofol on infarct size and neurological function. In conclusion, our results suggest that propofol plays a neuroprotective role in stroke by inhibiting the inflammatory pathway of NLRP1-caspase-1-caspase-6. Overall, these data suggest that propofol plays a key role in the inflammatory-dependent pathway after stroke, providing an important evidence for propofol as an effective strategy for neuroprotection in stroke.

4.
Med Sci Monit ; 26: e926755, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33024069

RESUMO

BACKGROUND Protein kinase membrane-associated tyrosine/threonine (PKMYT1) has been found in many tumors, but its association with clear cell renal cell carcinoma (ccRCC) remains unclear. MATERIAL AND METHODS PKMYT1 expression in ccRCC was examined in the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Tumor Immune Estimation Resource databases. The correlation between PKMYT1 expression and clinicopathological parameters was explored via the chi-square test. Receiver operating characteristic curves were used to estimate the diagnostic performance of PKMYT1. Kaplan-Meier curves, a Cox model, nomogram, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA) were used to evaluate the prognostic value and clinical utility of PKMYT1. Genes coexpressed with PKMYT1 in ccRCC were identified based on TCGA, the gene expression profiling interactive, and cBioPortal. Gene Set Enrichment Analysis revealed biological pathways associated with PKMYT1 in ccRCC. RESULTS Weighted gene coexpression network analysis identified PKMYT1 as one of the genes most significantly correlated with progression of histological grade. PKMYT1 was significantly upregulated in ccRCC compared with normal tissue (P<0.001), with a trend toward differentiating between individuals with ccRCC and those who were healthy (area under the curve=0.942). High PKMYT1 expression was correlated with unsatisfactory survival (hazard ratio=1.67, P=0.001), indicating that it is a risk factor for ccRCC. A nomogram incorporating PKMYT1 level was created and showed a clinical net benefit. PKMYT1 was strongly positively correlated with the anti-silencing function of 1B histone chaperone (ASF1B) gene in ccRCC. CONCLUSIONS PKMYT1 is upregulated in ccRCC and its presence indicates poor prognosis, making it a potential therapeutic target for ccRCC.

5.
Cell Mol Neurobiol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025417

RESUMO

The insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-ß signal pathways are both recognized as important in regulating cancer prognosis, such as the epithelial-to-mesenchymal transition (EMT) and cell invasion. However, cross-talk between these two signal pathways in glioblastoma multiforme (GBM) is still unclear. In the present study, by analyzing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE) 4412, GBM patients with higher IGF-1 levels exhibited poorer survival. Genes positively correlated with IGF-1 were enriched in EMT and TGF-ß signal pathways. IGF-1 treatment enhanced mesenchymal marker expressions and GBM cell invasion. A significant positive correlation was observed for IGF-1 with TGF-ß1 (TGFB1) or TGF-ß receptor 2 (TGFBR2), both of which participate in TGF-ß signaling and are risk genes in the GBM process. IGF-1 stimulation promoted both TGFB1 and TGFBR2 expressions. LY2157299, a TGF-ß signaling inhibitor, attenuated IGF-1-enhanced GBM cell invasion and mesenchymal transition. By analyzing IGF-1-regulated microRNA (miR) profiles, miR-4286 was found to be significantly downregulated in IGF-1-treated cells and could be targeted to both TGFB1 and TGFBR2. Overexpression of miR-4286 significantly attenuated expressions of the IGF-1-mediated mesenchymal markers, TGFB1 and TGFBR2. Using kinase inhibitors, only U0126 treatment showed an inhibitory effect on IGF-1-reduced miR-4286 and IGF-1-induced TGFB1/TGFBR2 expressions, suggesting that MEK/ERK signaling is involved in the IGF-1/miR-4286/TGF-ß signaling axis. Finally, our results suggested that miR-4286 might act as a tumor suppressive microRNA in inhibiting IGF-1-enhanced GBM cell invasion. In conclusion, IGF-1 is connected to TGF-ß signaling in regulating the mesenchymal transition and cell invasion of GBM through inhibition of miR-4286. Our findings provide new directions and mechanisms for exploring GBM progression.

6.
Nat Mater ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046858

RESUMO

The Dzyaloshinskii-Moriya interaction (DMI) between two magnetic moments mi and mj is of the form [Formula: see text]. It originates from spin-orbit coupling, and is at the heart of fascinating phenomena involving non-collinear magnetism, such as magnetic topological defects (for example, skyrmions) as well as spin-orbit torques and magnetically driven ferroelectricity, that are of significant fundamental and technological interest. In sharp contrast, its electric counterpart, which is an electric DMI characterized by its [Formula: see text] strength and describing an interaction between two polar displacements ui and uj, has rarely been considered, despite the striking possibility that it could also generate new features associated with non-collinear patterns of electric dipoles. Here we report first-principles simulations combined with group theoretical symmetry analysis which not only demonstrate that electric DMI does exist and has a one-to-one correspondence with its magnetic analogue, but also reveals a physical source for it. These findings can be used to explain and/or design phenomena of possible technological importance in ferroelectrics and multiferroics.

7.
Insects ; 11(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066376

RESUMO

Ecdysteroid titer determines the state of the cell cycle in silkworm (Bombyxmori) metamorphosis. However, the mechanism of this process is unclear. In this study, we demonstrated that the BmFoxO gene participates in the regulation of the cell cycle induced by 20-Hydroxyecdysone (20E) in BmN-SWU1 cells. The 20E blocks the cell cycle in the G2/M phase through the ecdysone receptor (EcR) and inhibits DNA replication. The 20E can promote BmFoxO gene expression. Immunofluorescence and Western blot results indicated that 20E can induce BmFoxO nuclear translocation in BmN-SWU1 cells. Overexpression of the BmFoxO gene affects cell cycle progression, which results in cell cycle arrest in the G0/G1 phase as well as inhibition of DNA replication. Knockdown of the BmFoxO gene led to cell accumulation at the G2/M phase. The effect of 20E was attenuated after BmFoxO gene knockdown. These findings increase our understanding of the function of 20E in the regulation of the cell cycle in B. mori.

8.
Polymers (Basel) ; 12(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066612

RESUMO

Carboxyl-type boronic acid copolymers (CBACs) were synthesized by a radical polymerization method and used for the preparation of polyvinyl alcohol (PVA)-based composite membranes via a solution mixture method. The as-prepared composite membranes exhibited a water uptake (WR) of 122.6-150.0%, an ion exchange capacity (IEC) of 0.0147-0.0518 mmol g-1, and excellent mechanical (elongation at break (Eb) of 103.8-148.4%, tensile strength (TS) of 38.7-58.6 MPa) and thermal stability. The alkali resistances of the as-prepared membranes were tested by immersing the samples into 2 mol L-1 NaOH solutions at 25 °C for 60 h, and the results were encouraging: the mass loss and swelling degree of the as-prepared membranes were in the ranges of 1.9-5.9% and 222.6-241.9%, respectively. The separation performances of the as-prepared membranes were evaluated by the diffusion dialysis (DD) process with an NaOH/Na2WO4 mixture at room temperature. The results demonstrated that the dialysis coefficients of hydroxide (UOH) were in the range of 0.0147-0.0347 m h-1, and the separation factors (S) were in the range of 29.5-62.6. The introduced carboxyl groups from CBACs and the -OH groups from PVA were both deemed to play significant roles in the promotion of ion transport: the -COO- groups formed negatively charged transport channels for Na+ by electrostatic attraction, and the -OH groups promoted the transport of OH- via hydrogen bonding.

9.
Theranostics ; 10(25): 11673-11689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052240

RESUMO

Hair regenerative medicine, a promising strategy for the treatment of hair loss, will likely involve the transplantation of autologous hair follicular stem cells (HFSCs) and dermal papilla cells (DPCs) into regions of hair loss. Cyclic hair regeneration results from the periodic partial activation of HFSCs. However, previous studies have not successfully achieved large-scale HFSC expansion in vitro without the use of feeder cells, with a lack of research focused on regulating HFSC fate for hair follicular (HF) regeneration. Hence, an emerging focus in regenerative medicine is the reconstruction of natural extracellular matrix (ECM) regulatory characteristics using biomaterials to generate cellular microenvironments for expanding stem cells and directing their fate for tissue regeneration. Methods: HFSCs were coated with gelatin and alginate using layer-by-layer (LbL) self-assembly technology to construct biomimetic ECM for HFSCs; after which transforming growth factor (TGF)-ß2 was loaded into the coating layer, which served as a sustained-release signal molecule to regulate the fate of HFSCs both in vitro and in vivo. In vitro experiments (cell culture and siRNA) were employed to investigate the molecular mechanisms involved and in vivo implantation was carried out to evaluate hair induction efficiency. Results: Nanoscale biomimetic ECM was constructed for individual HFSCs, which allowed for the stable amplification of HFSCs and maintenance of their stem cell properties. TGF-ß2 loading into the coating layer induced transformation of CD34+ stem cells into highly proliferating Lgr5+ stem cells, similar to the partial activation of HFSCs in HF regeneration. Thus, LbL coating and TGF-ß2 loading partially reconstructed the quiescent and activated states, respectively, of stem cells during HF regeneration, thereby mimicking the microenvironment that regulates stem cell fate for tissue regeneration during HF cycling. Improved HF regeneration was achieved when the two HFSC states were co-transplanted with neonatal mouse dermal cells into nude mice. Conclusion: This study provides novel methods for the construction of stem cell microenvironments and experimental models of HF regeneration for the treatment of hair loss.

10.
PLoS One ; 15(10): e0240077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052950

RESUMO

This paper uses resilience as a lens through which to analyse disasters and other major threats to patterns of criminal behaviour. A set of indicators and mathematical models are introduced that aim to quantitatively describe changes in crime levels in comparison to what could otherwise be expected, and what might be expected by way of adaptation and subsequent resumption of those patterns. The validity of the proposed resilience assessment tool is demonstrated using commercial theft data from the COVID-19 pandemic period. A 64 per cent reduction in crime was found in the studied city (China) during an 83-day period, before daily crime levels bounced back to higher than expected values. The proposed resilience indicators are recommended as benchmarking instruments for evaluating and comparing the global impact of COVID-19 policies on crime and public safety.

11.
Clin Neurol Neurosurg ; 199: 106282, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33045626

RESUMO

BACKGROUND: Treatment of ependymoma (EPN) is guided by associated tumor features, such as grade and location. However, the relationship between these features with treatments and overall survival in EPN patients remains uncharacterized. Here, we describe the change over time in treatment strategies and identify tumor characteristics that influence treatment and survival in EPN. METHODS AND MATERIALS: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 Registries (1973-2016) database, we identified patients with EPN microscopically confirmed to be grade II (EPN-GII) or III (EPN-GIII) tumors between 2004-2016. Overall survival (OS) was analyzed using Kaplan-Meier survival estimates and multivariable Cox proportional hazard models. A sub-analysis was performed by tumor location (supratentorial, posterior fossa, and spine). Change over time in rates of gross total resection (GTR), radiotherapy (RT), and chemotherapy (CS) were analyzed using linear regression, and predictors of treatment were identified using multivariable logistic regression models. RESULTS: Between 2004-2016, 1,671 patients were diagnosed with EPN, of which 1,234 (74 %) were EPN-GII and 437 (26 %) EPN-GIII. Over the study period, EPN-GII patients underwent a less aggressive treatment (48 % vs 27 %, GTR; 60 % vs 30 %, RT; 22 % vs 2%, CS; 2004 vs 2016; p < 0.01 for all). Age, tumor size, location, and grade were positive predictors of undergoing treatment. Univariate analysis revealed that tumor grade and location were significantly associated with OS (p < 0.0001 for both). In multivariable Cox regression, tumor grade was an independent predictor of OS among patients in the cohort (grade III, HR 3.89 [2.84-5.33]; p < 0.0001), with this finding remaining significant across all tumor locations. CONCLUSIONS: In EPN, tumor grade and location are predictors of treatment and overall survival. These findings support the importance of histologic WHO grade and location in the decision-making for treatment and their role in individualizing treatment for different patient populations.

12.
Biol Direct ; 15(1): 20, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076954

RESUMO

BACKGROUND: The nematode worm, Caenorhabditis elegans, is a saprophytic species that has been emerging as a standard model organism since the early 1960s. This species is useful in numerous fields, including developmental biology, neurobiology, and ageing. A high-quality comprehensive molecular interaction network is needed to facilitate molecular mechanism studies in C. elegans. RESULTS: We present the predicted functional interactome of Caenorhabditis elegans (FIC), which integrates functional association data from 10 public databases to infer functional gene interactions on diverse functional perspectives. In this work, FIC includes 108,550 putative functional associations with balanced sensitivity and specificity, which are expected to cover 21.42% of all C. elegans protein interactions, and 29.25% of these associations may represent protein interactions. Based on FIC, we developed a gene set linkage analysis (GSLA) web tool to interpret potential functional impacts from a set of differentially expressed genes observed in transcriptome analyses. CONCLUSION: We present the predicted C. elegans interactome database FIC, which is a high-quality database of predicted functional interactions among genes. The functional interactions in FIC serve as a good reference interactome for GSLA to annotate differentially expressed genes for their potential functional impacts. In a case study, the FIC/GSLA system shows more comprehensive and concise annotations compared to other widely used gene set annotation tools, including PANTHER and DAVID. FIC and its associated GSLA are available at the website http://worm.biomedtzc.cn .

13.
Eur J Med Chem ; 208: 112847, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33022479

RESUMO

Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 µM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.

14.
JAMA Netw Open ; 3(10): e2019440, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026449

RESUMO

Importance: Palliative radiotherapy (RT) is generally recommended for older patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis. A new combination treatment is therefore needed. Objective: To assess the efficacy and toxicity of RT plus icotinib vs RT alone in older patients with ESCC. Design, Setting, and Participants: This randomized, multicenter, open-label, phase II clinical trial was conducted in China, with enrollment between January 1, 2015, and October 31, 2016. Patients aged 70 years or older with clinical stage T2 to T4, N0/1, M0/1a unresectable (because of comorbidities, T4 disease, unresectable lymph node, or refused surgery) ESCC were randomized 1:1 to receive RT plus icotinib or RT alone. Radiation was prescribed at 60 Gy in 30 fractions in both groups, and icotinib was administered at a dosage of 125 mg 3 times a day in the RT plus icotinib group. The last follow-up was completed on June 30, 2019, and data were analyzed from July 1 to September 30, 2019. Interventions: Patients were randomized to either RT plus icotinib or RT alone. Main Outcomes and Measures: The primary end point was overall survival (OS). Treatment-related toxic effects were evaluated. Immunohistochemistry was performed to analyze epidermal growth factor receptor (EGFR) expression if available. Results: A total of 127 patients (median age, 76 years [range, 70-91 years]; 76 men [59.8%]) were enrolled and were eligible for survival analysis. Median OS was 24.0 (95% CI, 22.2-25.8) months in the RT plus icotinib group vs 16.3 (95% CI, 13.8-18.8) months in the RT group (hazard ratio, 0.53; 95% CI, 0.33-0.87; P = .008). No difference was observed in grades 3 or 4 adverse events. Patients with EGFR overexpression had a significantly better median overall survival (not reached vs 16.3 months [range, 2.6-45.1 months]; P = .03) in the RT plus icotinib group. Conclusions and Relevance: In this randomized clinical trial, icotinib plus RT was well tolerated and improved OS in older patients with ESCC relative to RT alone. Patients with EGFR overexpression benefitted more from icotinib with RT. Trial Registration: ClinicalTrials.gov Identifier: NCT02375581.

15.
Biomed Res Int ; 2020: 9809347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908931

RESUMO

We explored the difference in expression of tubulin alpha 1b (TUBA1B) between Wilms' tumor (WT) and normal tissues (NT) from in-house patients and databases, to determine TUBA1B expression in WT and the predictive pathways of coexpressed genes. In-house RNA-sequencing data were performed with WT and NT from three patients from our institute. Other four RNA-sequencing and microarray data were also downloaded from multiple public databases. The TUBA1B expression between WT and NT was analyzed by Student's t-test and meta-analysis. The correlation between the expression of TUBA1B and other genes in each study was analyzed. Genes with p < 0.05 and r > 0.5 were considered as the coexpressing genes of TUBA1B. Overlapping the coexpressed genes of the five studies, including three in-house patients (3 WT vs. 3 NT), GTEx-TARGET (126 WT vs. 51 NT), GSE2172 (18 WT vs. 3 NT), GSE11024 (27 WT vs. 12 NT), and GSE73209 (32 WT vs. 6 NT), were performed with limma and VennDiagram packages in R software. The website of WEB-based GEne SeT AnaLysis toolkit were used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations for the overlapped genes. The results showed that the relative expression of TUBA1B in WT tissues from in-house three patients was 280.0086, 141.7589, and 303.8292 and that in NT was 16.5836, 104.8141, and 12.79 (3 WT vs. 3 NT, p = 0.0285, ROC = 100%, SMD = 2.74). Student's t-test and meta-analysis in all studies revealed that the expression of TUBA1B was upregulated in WT tissues compared to that in NT (p < 0.05, SMD = 2.89, sROC = 0.98). Finally, the research identified the expression of TUBA1B in WT tissues was significantly upregulated than that in NT. The coexpressed genes of TUBA1B were enriched in the pathway of DNA replication, mismatch repair, cell cycle, pathogenic Escherichia coli infection, and spliceosome.

16.
Taiwan J Obstet Gynecol ; 59(5): 698-705, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917321

RESUMO

OBJECTIVE: The aim of this study was to examine the antitumor activity of hinokitiol for its clinical application in the treatment of human cervical carcinoma. MATERIALS AND METHODS: Cervical carcinoma HeLa cells were treated by different concentrations of hinokitiol. Flow cytometry was used to analyze cell cycle. Senescence-associated ß-galactosidase (SA-ß-gal) assay was used to identify senescent cells. The effects of hinokitiol on EGF-induced cell migration were determined by wound healing and transwell migration assays. Western blot was used to detect proteins involved in cell cycle progression, apoptosis, autophagy, and EGF-induced signaling pathways. RESULTS: Hinokitiol suppressed cell viability in a dose-dependent manner. Flow cytometric analysis indicated that hinokitiol treatment resulted in cell cycle arrest at G1 phase, with reduced number of cells in the G2/M phase. Western blot analysis further demonstrated that hinokitiol treatment increased the levels of p53 and p21, and concomitantly reduced the expression of cell cycle regulatory proteins, including cyclin D and cyclin E. SA-ß-gal assay showed that hinokitiol treatment significantly induced ß-galactosidase activity. In addition, treatment with hinokitiol increased the accumulation of the autophagy regulators, beclin 1 and microtubule-associated protein 1 light chain 3 (LC3-II), in a dose-dependent manner; however, it did not induce caspase-3 activation and poly ADP ribose polymerase (PARP) cleavage. In addition, epidermal growth factor-induced cell migration and c-Jun N-terminal kinase (JNK) and focal adhesion kinase (FAK) phosphorylation were significantly inhibited by hinokitiol. CONCLUSION: Our findings revealed that hinokitiol might serve as a potential therapeutic agent for cervical carcinoma therapy.

17.
Mater Sci Eng C Mater Biol Appl ; 117: 111344, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919691

RESUMO

Myocardial tissue engineering has attracted increasing awareness for heart failure, and researchers are committed to developing an appropriate biological material to reconstruct myocardial tissues. Here, we applied a simple and high-throughput method to fabricate a three-dimensional (3D) partially reduced graphene oxide (PRGO) foam chip, whose structure, properties and biocompatibility confirmed that it is a suitable material for myocardial tissue engineering. The PRGO foam was produced based on a reduction reaction that occurred at the interface between the graphene oxide (GO) solution and Ni foam; as the Ni foam scaffold was dissolved in an HCl solution, the PRGO foam was harvested. After the PRGO foam was freeze-dried, its elasticity property was evaluated, and primary cardiomyocytes obtained from 2-day-old SD rats were cultured in the 3D foam. The results demonstrated good cell adherence, spreading, activity, organization and beating function in the PRGO foam during the long-term culturing process, which proved that the PRGO foam obtained by this method had application potential for myocardial tissue engineering.

18.
Cell Mol Life Sci ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910224

RESUMO

It is critical to specify a signal that directly drives the transition that occurs between cell states. However, such inferences are often confounded by indirect intercellular communications or secondary transcriptomic changes due to primary transcription factors. Although FGF is known for its importance during mesoderm-to-endothelium differentiation, its specific role and signaling mechanisms are still unclear due to the confounding factors referenced above. Here, we attempted to minimize the secondary artifacts by manipulating FGF and its downstream mediators with a short incubation time before sampling and protein-synthesis blockage in a low-density angioblastic/endothelial differentiation system. In less than 8 h, FGF started the conversion of KDRlow/PDGFRAlow nascent mesoderm into KDRhigh/PDGFRAlow angioblasts, and the priming by FGF was necessary to endow endothelial formation 72 h later. Further, the angioblastic conversion was mediated by the FGFR1/BRAF/MEK/ERK pathway in mesodermal cells. Finally, two transcription factors, ETV2 and LMO2, were the early direct functional responders downstream of the FGF pathway, and ETV2 alone was enough to complement the absence of FGF. FGF's selective role in mediating the first-step, angioblastic conversion from mesoderm-to-endothelium thus allows for refined control over acquiring and manipulating angioblasts. The noise-minimized differentiation/analysis platform presented here is well-suited for studies on the signaling switches of other mesodermal-lineage fates as well.

19.
Chem Commun (Camb) ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926055

RESUMO

Amorphous Zn-rich nitrogen-doped carbon-based microstars are synthesized using an ionic liquid-assisted method and annealing process. The microstars exhibit a high reversible capacity of 756 mA h g-1 and a capacity retention of 98% after 120 cycles at 0.5 A g-1 due to their large surface area, hierarchical nanopores, and uniform distribution of zinc and nitrogen.

20.
J Neuroinflammation ; 17(1): 263, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891159

RESUMO

BACKGROUND: Spinal cord injury (SCI) causes neurological dysfunction with devastating consequences. SCI pathogenesis is accompanied by inflammasome activation and neuronal damage. But the spatial pattern and the time course of neuronal pyroptosis and apoptosis after SCI should be further elucidated. The microglial voltage-gated proton channel (Hv1) is implicated in reactive oxygen species (ROS)-induced neuronal damage following ischemic stroke. However, there is a lack of quantification on the neuronal pyroptosis and apoptosis associated with microglial Hv1 after SCI. METHODS: We analyzed spatial and temporal characteristics of neuronal pyroptosis and apoptosis following SCI and investigated the effects of Hv1 deficiency on neuronal pyroptosis and the nod-like receptor 3 (NLRP3) inflammasome pathway by using a mouse model of SCI. We tested the effects of Hv1-deficient microglia on ROS production in vivo and examined the relationship between ROS and neuronal pyroptosis in vitro. RESULTS: We observed that apoptosis was detected closer to the injury core than pyroptosis. The incidence of neuronal apoptosis peaked on day 1 after SCI and occurred before pyroptosis. Hv1 deficiency reduced neuronal apoptosis and NLRP3-inflammasome-mediated pyroptosis, improved axonal regeneration, and reduced motor deficits. SCI led to elevated ROS levels, whereas Hv1 deficiency downregulated microglial ROS generation. In vitro, ROS upregulated neuronal pyroptosis and activated the NLRP3 inflammasome pathway, both of which were reversed by addition of a ROS scavenger. Our results suggested that microglial Hv1 regulated neuronal apoptosis and NLRP3-induced neuronal pyroptosis after SCI by mediating ROS production. CONCLUSION: Following SCI, neuronal pyroptosis lasted longer and occurred farther away from the injury core compared with that of neuronal apoptosis. Microglial Hv1 deficiency downregulated microglial ROS generation and reduced apoptosis and NLRP3-induced neuronal pyroptosis. Our findings may provide novel insights into Hv1-associated mechanisms underlying neuronal damage after SCI.

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