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1.
Adv Mater ; : e2000208, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32147886

RESUMO

Effective reversal of tumor immunosuppression is of critical importance in cancer therapy. A multifunctional delivery vector that can effectively deliver CRISPR-Cas9 plasmid for ß-catenin knockout to reverse tumor immunosuppression is constructed. The multi-functionalized delivery vector is decorated with aptamer-conjugated hyaluronic acid and peptide-conjugated hyaluronic acid to combine the tumor cell/nuclear targeting function of AS1411 with the cell penetrating/nuclear translocation function of TAT-NLS. Due to the significantly enhanced plasmid enrichment in malignant cell nuclei, the genome editing system can induce effective ß-catenin knockout and suppress Wnt/ß-catenin pathway, resulting in notably downregulated proteins involved in tumor progression and immunosuppression. Programmed death-ligand 1 (PD-L1) downregulation in edited tumor cells not only releases the PD-1/PD-L1 brake to improve the cancer killing capability of CD8+ T cells, but also enhances antitumor immune responses of immune cells. This provides a facile strategy to reverse tumor immunosuppression and to restore immunosurveillance and activate anti-tumor immunity.

2.
J Fish Biol ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162333

RESUMO

Myeloid differentiation factor 88 (Myd88) plays an important role in both innate and adaptive immune response. In this study, the full-length complementary DNA (cDNA) of myd88 from Misgurnus anguillicaudatus was characterized. The myd88 cDNA is 1333 bp in length and contains an 855 bp open reading frame encoding a predicted protein of 284 amino acids. The predicted protein possesses typical Myd88 domain structural features including a death domain in the N-terminus, and box 1, 2, and 3 motifs of the Toll/IL-1 receptor domain in the C-terminus. Quantitative real-time PCR (qRT-PCR) revealed that myd88 messenger RNA (mRNA) was ubiquitously expressed in all examined tissues, especially highly in brain, kidney, blood, intestines and liver. qRT-PCR and western blotting were used to determine the mRNA and protein levels of Myd88 after Aeromonas veronii challenge, respectively. The Myd88 was remarkably upregulated in response to infection of A. veronii. These results suggested that Myd88 may play a vital role during the immune response of M. anguillicaudatus against bacterial infection.

3.
Chemistry ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32162421

RESUMO

The metal-organic frameworks (MOFs) with long persistent luminescence (LPL) have caused widespread attention due to potential applications in displaying, anti-counterfeiting, and so on. However, MOF materials are often with large pore size, which restricts the formation of efficient inter- and intramolecular interactions to realize LPL. Herein, we report a new approach to achieve LPL in MOFs by multi-fold interpenetration of discrete frameworks. By the comparison between 3-fold and 2-fold interpenetrating MOFs, we found that the former with higher multiplicity and denser frameworks can be endowed with enhanced inter- and intramolecular interactions, and thus prolonged long persistent luminescence is obtained. Meanwhile, metal cluster and heavy halogen effect could also arouse variations in LPL durations and colours.

4.
Drug Des Devel Ther ; 14: 731-744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158192

RESUMO

Objective: This study was to investigate the mechanism of inflammatory pathology modification induced by ox-LDL in endothelial cells. Methodology: In this study, we firstly investigated the efflux of cholesterol of endothelial cells under the treatment of ox-LDL, and cell proliferation, ROS production, cell apoptosis was measured. Further, proteins of ASK1, NLRP3 inflammasomes and endoplasmic reticulum stress response were detected. Afterwards, ASK1 inhibitor (GS-4997) or endoplasmic reticulum stress (ERS) inhibitor (4-PBA) was used to measure the performance of endothelial cells. Results: In this study, endothelial cells were treated with ox-LDLs alone or in combination with a GS-4997 or 4-PBA. Results showed that ox-LDLs attenuated the efflux of cholesterol from endothelial cells in a dose-dependent manner. Ox-LDLs inhibited the proliferation of endothelial cells, and induced their apoptosis and production of reactive oxygen species (ROS). Additionally, ox-LDLs upregulated the levels of phosphorylated ASK1, ERS-related proteins (chop, p-PERK, GRP78, and p-IRE-1), and inflammation-associated proteins (NLRP3, IL-1ß, and caspase 1) in endothelial cells. Moreover, we proved that GS-4997 could partly reverse ox-LDL-mediated cell proliferation, apoptosis, ROS production, and inflammation in endothelial cells, and increase cholesterol efflux. We also found that 4-PBA could attenuate the effects of ox-LDLs on endothelial cell cholesterol efflux, proliferation, apoptosis, ROS production, and inflammation. Conclusion: Our results suggest that cholesterol efflux from endothelial cells is reduced by ox-LDLs, and these reductions in cholesterol efflux are accompanied by increased NLRP3 inflammasome signaling, ASK1 and higher levels of endoplasmic reticulum stress. Our results suggest this axis as potential targets for treating atherosclerosis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32132346

RESUMO

BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel minimally invasive intervention for treating esophageal achalasia. Previous publications have proved its excellent efficacy and safety, and even shown it could improve patients' quality of life (QoL). So, we conducted this study to explore the changes of QoL following POEM. METHODS: A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane Library covering the period from January 2009 to April 2019. The statistical analysis was carried out using Review Manager 5.3. RESULTS: A total of 12 studies including 549 patients were identified, which assessed the QoL using validated questionnaires administered. After POEM, the SF-36 questionnaire score of each domain (physical function, role physical function, body pain, general health (GH), social function, vitality, emotional role function, mental health) was significantly increased (p < 0.05). Meanwhile, mental component scale (MCS) and physical component scale (PCS) scores were all improved in patients after POEM procedure (MCS: 12.11, 95% confidence interval [CI], 4.67-19.55, p = 0.001, I2 = 88%, PCS: 17.01, 95% CI, 2.91-31.11, p = 0.02, I2 = 97%). The gastroesophageal reflux disease health-related quality of life questionnaires (GERD-HRQL) also decreased significantly after POEM (13.01, 95% CI, 9.98-16.03, p < 0.00001, I2 = 30%). CONCLUSIONS: Our current evidence suggests there is significant improvement in QoL after POEM procedure.

7.
Can J Gastroenterol Hepatol ; 2020: 7920715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32211350

RESUMO

Background: The incidence of diabetic gastroparesis (DGP) is mainly blamed to abnormity of interstitial cells of Cajal (ICCs). Autophagy could degrade damaged proteins and organelles to keep intracellular homeostasis, and it could directly influence structure and number of cells. In this study, we aimed to figure out the relationship between DGP and autophagy of ICCs. Methods: Sixty Sprague-Dawley (SD) rats were randomly divided into normal control group (NC, 10) and modeling group (50). Rats in the modeling group were injected 2% streptozotocin (STZ) and fed with high-glucose and high-fat diet for 8 weeks in order to establish DGP rat model. After modeling, 30 successfully modeled rats were randomly selected and separated into diabetic gastroparesis group (DGP, 10), GDP rats with electroacupuncture group (EA, 10), and GDP rats with metoclopramide group (MP, 10). When the intervention was completed, blood glucose was measured by ONE TOUCH glucometer and gastrointestinal propulsive rate was detected through measuring optical density. Autophagosomes were observed under transmission electron microscope (TEM). The expression of LC3 protein and P62 protein was measured by Western blot. When ICCs were transfected with GFP-RFP-LC3 plasmid, autophagy flux was observed by laser scanning confocal microscope. Results: (1) After intervention, compared with blood glucose of rats in the NC group, all of the DGP, EA, and MP groups were remarkably increased (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01). (2) Compared with gastrointestinal propulsive rate of rats in the NC group, no matter gastric emptying rate or intestinal propulsive rate, the EA and MP groups were significantly reduced (P < 0.01); compared with the NC group, gastric emptying rate and intestinal propulsive rate in the EA group were obviously decreased (P < 0.05, P < 0.01); compared with the DGP group, the EA and MP groups were increased significantly (P < 0.01). (3) Compared with the NC group, intensity of RFP and GFP in the DGP group was obviously increased (P < 0.05, P < 0.01), in other words, the DGP group accompanying suppression of autophagy; compared with the DGP group, intensity of RFP and GFP in the EA group was decreased significantly (P < 0.05, P < 0.01). (4) There was no autophagosome in the NC group, and an autophagosome existed in the DGP group. Both EA and MP groups found autophagy. (5) When coming to LC3 II/LC3 I, compared with the NC group, the ratio was enhanced in the DGP and EA groups (P < 0.01, P < 0.05); compared with the DGP group, LC3 II/LC3 I was dramatically decreased in the MP and EA groups (P < 0.01). (6) As the substrate of degradation, the expression of P62 in the other three groups was significantly increased (P < 0.01) compared with the NC group; compared with the DGP group, the amount of P62 in the EA and MP groups was reduced greatly (P < 0.01). Conclusion: The impaired autophagy flux in ICCs is the pathological basis of diabetic gastroparesis, blaming to fusion dysfunction of autophagosome and lysosome and electroacupuncture (EA) could ease the suppression of autophagy to improve gastric motility.

8.
Nucleic Acids Res ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187359

RESUMO

Frameshift mutations are generally considered to be lethal because it could result in radical changes of the protein sequence behind. However, the protein of frameshift mutants of a type I toxin (ibsc) was found to be still toxic to bacteria, retaining the similar function as wild-type protein to arrest the cellular growth by impairing the membrane's integrity. Additionally, we have verified that this observation is not an individual event as the same phenomenon had been found in other toxins subsequently. After analyzing the coding sequence of these genes, we proposed a hypothesis to search this kind of hidden gene, through which a dihydrofolate reductase-encoding gene (dfrB3) was found out. Like the wild-type reductase, both +1 and -1 frame-shifted proteins of dfrB3 gene were also proved to catalyze the reduction of dihydrofolate to tetrahydrofolate by using NADPH.

9.
Mol Biol Rep ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222917

RESUMO

Quantitative real-time PCR (qRT-PCR) has been widely used for studying gene expression at the transcript level. Its accuracy usually relies on the reference genes that are utilized for data normalization. Miscanthus sinensis, a perennial C4 grass with high biomass and strong resistance to adversities, is often utilized as a high value energy crop. However, no reliable reference genes have been investigated for normalizing gene expression for this species. In this study, 12 candidate reference genes were selected to identify their stability under five different abiotic stress treatments (drought, salt, cadmium, chromium and arsenic) by using geNorm, NormFinder, BestKeeper and RefFinder softwares. The results showed that 18S rRNA and Unigene33312 were the best reference genes under drought treatments. Unigene33312 and Unigene33024 were found to be the most stably expressed genes under salt stress and Cd stress. Moreover, Unigene33024 and PP2A were the most suitable reference genes under Cr stress and Unigene33024 and Sb09g019750 were deemed more suitable reference genes under As stress. In total, considering all the samples, Unigene33024 and PP2A were the most stable genes while ACTIN and Unigene26576 were the least stable reference genes for internal control. The expression patterns of two target genes (Cu/Zn SOD and CAT) were used to further verify those selected reference genes under different conditions. The results showed that the most and the least stable reference genes had clearly different expression patterns. This work comprehensively estimated the stability of reference genes in M. sinensis which may give insight to the reference genes selection in other tissues as well as other related varieties. These suggested reference genes would assist in further putative gene expression validation in M. sinensis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32203015

RESUMO

OBJECTIVE: For heart transplantation, donor heart status needs to be evaluated during normothermic ex situ perfusion (ESHP). Left ventricular end-systolic elastance (Ees) measures the left ventricular contractile function, but its estimation requires the occlusion of the left atrium line in the ESHP, which may cause unnecessary damage to the donor heart. We present a novel method to quantify Ees based on hemodynamic parameters obtained from only one steady-state PV loop in ESHP. METHODS: Ees was obtained by the end-systolic point (Pes, Ves) and the volume axis intercept point of Ees (V0). V0 was estimated through the support vector machine regression (SVR) method using parameters derived from the measured steady-state PV loop. To achieve high V0 estimation accuracy, a filter-based support vector machine recursive feature elimination method (SVM-RFE) algorithm selected the parameters for V0 estimation. Hemodynamic parameter samples (n = 101) obtained from ESHP experiments with pig s hearts were used to train the Ees calculation model. Early post-transplantation outcomes in six heart transplantation experiments were then estimated from the trained Ees calculation model. RESULTS: Ees calculated by the proposed method agreed well with conventional multi-beat estimates obtained by the occlusion process (r = 0.88, p < 0.001, n = 101) and was capable of predicting the early post-transplant cardiac index (r = 0.84, p < 0.05, n = 6). CONCLUSION: This method effectively assesses left ventricular contractility during ESHP and predicts early post-transplant outcomes in the porcine model. SIGNIFICANCE: Our approach is the first to quantify Ees by estimating V0 from steady-state beats in ESHP for accurately predicting early post-transplantation outcomes.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32220495

RESUMO

Many degenerative diseases of the central nervous system (CNS) are associated with demyelination. Oligodendrocyte precursor cells (OPCs) are potential stem cells that can differentiate into oligodendrocytes (OLs) and promote myelination. Promoting the proliferation of OPCs is key to stimulating remyelination and treating neurodegenerative diseases. Herein, we report that astrocytes (ASTs) could increase exosomal secretion of OPCs to promote their proliferation via ITGB4-mediated cell adhesion. Our results demonstrate that ASTs can regulate the proliferation of OPCs through ITGB4-mediated exosomal secretion. OPC proliferation is significantly increased after direct-contact culture with ASTs. Gene ontology (GO) and KEGG pathway analyses reveal that ITGB4/extracellular exosome are closely related to OPC proliferation. siRNA ITGB4 decreases exosomal secretion and OPC proliferation. ITGB4/exosomes remarkably promote OPC transition from G1 to S phase. Furthermore, exosomes can alleviate the inhibitory effect of ITGB4 knockdown on OPC proliferation. Collectively, ASTs regulate OPC exosomal secretion via ITGB4, which could be a valuable approach for promoting OPC proliferation. This strategy may represent a potential treatment for neurological diseases caused by demyelination.

12.
J Cardiothorac Surg ; 15(1): 33, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019564

RESUMO

BACKGROUND: Presently, endoscopic submucosal tunnel dissection (ESTD) has been a novel therapy for superficial esophageal neoplastic lesions (SENL), especially for circumferential neoplastic lesions. A number of studies have reported the clinical application of ESTD with promising outcomes. Therefore, we conducted a systematic review and meta-analysis to evaluated the efficacy and safety of ESTD for SENL . METHODS: From 2013 to November 2018, Pubmed, Embase and Cochrane databases were searched to determine studies reporting ESTD treatment of SENL. Weighted pooled rates (WPR) were calculated for en bloc resection, R0 resection and complication of ESTD. Risk ratios (RR) were calculated and pooled to compare the clinical outcomes of ESTD with ESD for SENL. RESULTS: A total of 9 studies involving 494 patients with 518 esophageal neoplastic lesions were included in our study. WPR for en bloc resection and R0 resection of ESTD was 97.0% (95% CI: 94.7-98.3%) and 84.1% (95% CI: 80.5-87.1%), respectively. WPR for complication was 40.0% (95% CI: 25.8-56.1%). Two studies with 265 patients compared the performance of ESTD with ESD. Pooled RR for en bloc resection and R0 resection was 1.04 (95% CI: 0.95-1.14, P = 0.42) and 1.01 (95% CI: 0.93-1.10, P = 0.73), respectively. Pooled RR for complication was 0.68 (95% CI: 0.46-1.01, P = 0.05). CONCLUSION: Our study showed that ESTD is effective for treating SENL with high en bloc resection rate and R0 resection rate, but accompanying by a relatively high complications.

13.
Cell Rep ; 30(8): 2791-2806.e5, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32101752

RESUMO

Intervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/NODAL and WNT and inhibition of BMP pathways. By day 5 of differentiation, hPSC-derived cells express notochordal cell characteristic genes. After activating the TGF-ß pathway for an additional 15 days, qPCR, immunostaining, and transcriptome data show that a wide array of NP markers are expressed. Transcriptomically, the in vitro-derived cells become more like in vivo adolescent human NP cells, driven by a set of influential genes enriched with motifs bound by BRACHYURY and FOXA2, consistent with an NP cell-like identity. Transplantation of these NP-like cells attenuates fibrotic changes in a rat disc injury model of disc degeneration.

14.
BMC Cardiovasc Disord ; 20(1): 14, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931720

RESUMO

BACKGROUND: This study aims to evaluate the ADL(activity of daily living) of patients with acute cerebral infarction through BI scoring, in order to observe its predictive value in the prognosis of these patients. METHODS: According to the inclusion and exclusion criteria, patients with acute anterior circulation cerebral infarction were included in the present study. Then, the BI scoring was analyzed through five grades, in order to further investigate the dose-response relationship between BI scoring and mortality risk in patients with cerebral infarction. The receiver operating characteristic (ROC) curves for BI-scored patients were drawn, and the predictive authenticity of the Barthel scale in prognostic prediction for patients with cerebral infarction was estimated. RESULTS: The difference in BI scores between the survival group and death group were statistically significant (t = 10.029, P < 0.05), in which the score was lower in the death group than in the survival group. According to the linear trend ×2-test, the decrease in BI score indicates an increase in mortality risk in patients with cerebral infarction. The area under the curve (AUC) of the ROC curve was 0.794 with a P-value of < 0.05. CONCLUSION: BI scoring is a highly valuable scoring system for the prognostic prediction of patients with acute cerebral infarction.

15.
BMC Gastroenterol ; 20(1): 11, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937264

RESUMO

BACKGROUND: Previous studies have indicated that disease activity, psychological symptoms and social support were associated with health-related quality of life (HRQoL) in patients with inflammatory bowel diseases(IBD). However, it is unclear how disease activity, psychological symptoms and social support interact to affect HRQoL. The main purpose of this study was to examine the mediation effect of psychological symptoms in the relationship between disease activity, social support and HRQoL. METHODS: This was a cross-sectional study, which collected data using convenience sampling, between December 2016 and March 2018, from the Third XiangyaHospital of Central South University in Changsha, China. An online self-administered questionnaire (including demographic and clinical information), Inflammatory Bowel Disease Questionnaire, Disease Activity Indices scale, Hospital Anxiety and Depression Scale and Social Support Rating Scale, were administered to each participant. Descriptive statistics and Pearson's correlations were used to summarize data, whereas PROCESS analysis was performed to examine the pre-specified mediation effect. RESULTS: A total of 199 patients with IBD were included. Disease activity indices (DAI) and hospital anxiety and depression (HAD) were negatively correlated with HRQoL (ß = - 3.37, - 2.54 respectively, P < 0.001), while social support was positively correlated with HRQoL (ß = 1.38, P < 0.01). HAD partially mediated the negative relationship between DAI and HRQoL (ß = - 0.83, P < 0.001) with the mediation effect ratio of 24.6%, and completely mediated the positive relationship between social support and HRQoL (ß = 1.20, P < 0.001). CONCLUSIONS: Psychological symptoms acted as a mediator in the relationship between disease activity, social support and HRQoL. Interventions to improve HRQoL in patients with IBD should take into account the mediation effect of psychological symptoms.

16.
Acta Haematol ; : 1-6, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31982874

RESUMO

Both congenital hypodysfibrinogenemia and factor XI deficiency are rare coagulopathies caused by mutations within the fibrinogen and F11 genes, respectively. To investigate the pathogenesis of combined congenital hypodysfibrinogenemia with factor XI (FXI) deficiency in a Chinese family, coagulation assays, FXI activity (the 1-stage method), fibrinogen activity (the Clauss method), and antigen (prothrombin time [PT]-derived method) were performed. The sequences of fibrinogen genes and F11 were amplified by PCR and analyzed by direct sequencing. The proband as well as his grandmother, father, aunt, and sister showed a low plasma concentration of fibrinogen measured by the Clauss method and a slightly decreased result by the PT-derived method; finally, c.1097A>G in exon 8 of FGG was detected in the pedigree, which caused His340Arg mutation. His grandfather had a slightly prolonged activated partial thromboplastin time (APTT) due to low FXI activity. FXI deficiency was a compound heterozygote inherited with missense mutations of c.434A>G in exon 5 as well as c.1253G>T in exon 11 which caused HGV p.His145Arg and Gly400Val mutations, respectively. The grandfather had no qualitative or quantitative defect in fibrinogen. The proband and his father and aunt had c.434A>G at the exon 5 mutation site and no decrease in FXI activity. His mother had no fibrinogen or F11 gene mutations. Plasma fibrin polymerization was delayed. The proband in our study showed typical changes of congenital hypodysfibrinogemia in the clotting analyses with delayed fibrin polymerization, but although he was a heterozygous carrier of the c.434A>G variant in the F11 gene, he had no decrease in FXI activity and no bleeding tendency, thus questioning the pathogenicity of the identified variant in the F11 gene. To our knowledge, this is the first report of a case of combined hypodysfibrinogenemia and FXI deficiency confirmed by molecular genetic tests.

17.
ACS Appl Mater Interfaces ; 12(5): 6489-6495, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927977

RESUMO

Growing interest has been received in metallic foams for their combined features of metals and porous structures. Coating metals on polymers have been the most prevalent method to fabricate hybrid metallic foams to inherit both the merits of metals and the mechanical flexibility of polymers. However, direct coating metals on foams is challenging and requires tedious synthesis, such as electrolysis and chemical reduction. This work reported a facile strategy to build hybrid metallic foams via in situ foaming of liquid metals (LM) and polyurethane. The fluidity and incompatibility of LM with porous polyurethane allow the coating of LM on polymers. LM-Foams exhibit high electrical conductivity (3.9 × 104 S/m), low density (ρ < 1 g/cm3), phenomenal elasticity (recover at 95% strain), and excellent mechanical stability (stable with 1000 compressive cycles). Interestingly, the ease of deformation for fluidic fillers in elastic polyurethane generates additional resistive change under pressure, showing unique sensory behaviors which were not observed in conventional conductive foams, such as high response sensitivity (gauge factor >25), short response time (202 ms), and outstanding electrical stability. The nonuniform size distribution of pores leads LM-Foams to show unusual position-dependent sensitivity, enabling advanced applications as password pads and electrical protection foams.

18.
J Proteome Res ; 19(2): 769-780, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31916766

RESUMO

The global emergence of soil salinization poses a serious challenge to many countries and regions. γ-Aminobutyric acid (GABA) is involved in systemic regulation of plant adaptation to salt stress but the underlying molecular and metabolic mechanism still remains largely unknown. The elevated endogenous GABA level by the application of exogenous GABA improved salt tolerance associated with the enhancement of antioxidant capacity, photosynthetic characteristics, osmotic adjustment (OA), and water use efficiency in creeping bentgrass. GABA strongly upregulated transcript levels of AsPPa2, AsATPaB2, AsNHX2/4/6, and AsSOS1/20 in roots involved in enhanced capacity of Na+ compartmentalization and mitigation of Na+ toxicity in the cytosol. Significant downregulation of AsHKT1/4 expression could be induced by GABA in leaves in relation to maintenance of the significantly lower Na+ content and higher K+/Na+ ratio. GABA-depressed aquaporin expression and accumulation induced declines in stomatal conductance and transpiration, thereby reducing water loss in leaves during salt stress. For metabolic regulation, GABA primarily enhanced sugar and amino acid accumulation and metabolism, largely contributing to improved salt tolerance through maintaining OA and metabolic homeostasis. Other major pathways could be related to GABA-induced salt tolerance including increases in antioxidant defense, heat shock proteins, and myo-inositol accumulation in leaves. Integrative analyses of molecular, protein, metabolic, and physiological changes reveal systemic functions of GABA in regulating ionic, water, and metabolic homeostasis in nonhalophytic creeping bentgrass under salt stress.

19.
Mol Med Rep ; 21(3): 1336-1345, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922214

RESUMO

The aim of the present study was to investigate the protective effect of Kruppel­like factor 15 (KLF15) overexpression on heart failure (HF) induced by left ventricular (LV) pressure overload in mice. Wild­type (WT) mice and cardiac­specific KLF15­overexpressed transgenic (TG) mice were selected as research subjects, and an LV pressure overload model was constructed by ascending aortic constriction surgery. Changes in cardiac morphology and function, and ultrastructure and molecular expression were observed via M­mode echocardiography, histological and immunohistochemical staining, ELISA and western blotting at 2 and 6 weeks of LV overload. WT and TG mice subjected to 2 weeks of overload displayed adaptive LV hypertrophy characterized by ventricular thickness, cardiomyocyte size, ejection fraction and fractional shortening of heart­lung weight ratio and KLF15, and increases in vascular endothelial growth factor (VEGF) expression without other pathological changes. WT mice subjected to 6 weeks of overload displayed enlargement of the LV chamber, severe interstitial remodeling, and HW/LW, cardiac capillary and heart function decline, accompanied by downregulated expression of KLF15 and VEGF, and upregulated expression of connective tissue growth factor, phosphorylated p38 (p­p38) and phosphorylated Smad3 (p­Smad3). In contrast, TG mice exhibited improved resistance to 6 weeks of overload and a slighter molecular expression response compared with WT mice. KLF15 was revealed to be a critical factor regulating the expression of CTGF, VEGF, p­p38 and p­Smad3, and could alleviate the progression from adaptive LV hypertrophy to decompensatory cardiac insufficiency.

20.
Int J Surg Pathol ; : 1066896920901764, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992096

RESUMO

Large cell neuroendocrine carcinoma (LCNEC) of the endometrium is an exceedingly rare histologic subtype of endometrial cancer (0.8%). These tumors are highly aggressive with a propensity for metastasis and have a poor prognosis. Among the 17 cases reported to date, 9 cases were pure large cell neuroendocrine tumors and 8 were collision tumors of LCNEC with endometrial carcinomas (7 endometrioid and 1 serous). In this article, we report a case of collision tumor composed of an endometrial LCNEC and a low-grade endometrial stromal sarcoma (LGESS). The patient was a 48 year-old woman who presented with a large abdominal mass for about 10 years and underwent total hysterectomy, bilateral salpingo-oophorectomy, and tumor debulking. Microscopic evaluation demonstrated an LGESS with extensive osseous metaplasia that penetrated through the myometrium and invaded into pelvic and abdominal cavity, forming a 40.0-cm mass. Cytogenetic analysis of the LGESS revealed an abnormal female karyotype (45, XX) with multiple structural abnormalities. Incidentally, small foci of LCNEC were identified within the endometrium. The LCNEC focally invaded the myometrium with involvement of the endocervix, extensive lymph-vascular space invasion, and metastases to bilateral ovaries. Subsequently, the patient was treated with cisplatin/etoposide chemotherapy and had been doing well for about a year until presenting with recurrence of LCNEC in the abdomen. She passed away a month later due to medical complications. This report reveals an extremely rare endometrial collision tumor with unusual pathologic features and clinical presentations.

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