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1.
Phys Rev Lett ; 125(14): 143605, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33064545

RESUMO

We propose how to achieve nonreciprocal quantum entanglement of light and motion and reveal its counterintuitive robustness against random losses. We find that by splitting the counterpropagating lights of a spinning resonator via the Sagnac effect, photons and phonons can be entangled strongly in a chosen direction but fully uncorrelated in the other. This makes it possible both to realize quantum nonreciprocity even in the absence of any classical nonreciprocity and also to achieve significant entanglement revival against backscattering losses in practical devices. Our work provides a way to protect and engineer quantum resources by utilizing diverse nonreciprocal devices, for building noise-tolerant quantum processors, realizing chiral networks, and backaction-immune quantum sensors.

2.
Life Sci ; : 118572, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065147

RESUMO

AIM: Apoptosis of endothelial cells (ECs) is a crucial factor in blood-spinal cord barrier (BSCB) disruption post spinal cord injury (SCI). Insulin-like growth factor-1 (IGF-1) is a protective cytokine that plays an important role in multiple diseases, whereas the distinct role in SCI-induced remains critical questions to address. Here we designed to explore the role and underlying mechanism of IGF-1 in endothelial damage after SCI. MAIN METHODS: In the current study, we established mouse microvascular endothelial cells (MVECs) injury model via LPS and cDNA of IGF-1 was transfected into MVECs. In vivo SCI mice, overexpression of IGF-1 (SCI-IGF-1) and its corresponding empty vehicle (SCI-NC) were conducted using lentivirus, then apoptosis degree, component of tight junction, and inflammatory damage were evaluated. KEY FINDINGS: IGF-1 treatment in MVECs displayed a milder apoptosis and cell damage under LPS insult. IGF-1 increased the level of PI3K/AKT pathway, which impeded the procedure of apoptosis. Blocking of PI3K/AKT pathway markedly neutralized the effect of IGF-1 treatment. Transfection of excess IGF-1 into SCI mice significantly corrected microenvironment of neural tissue repair, reduced area of injured core and improved functional recovery with greater activation of PI3K/AKT pathway. SIGNIFICANCE: The results above argue that the promising roles played by IGF-1 is potentially vital for developing effective future therapies in SCI.

3.
Inflammation ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067662

RESUMO

Similar to other immune-mediated diseases, IgG4-related disease (IgG4-RD) is the disease that develops in genetically susceptible individuals exposed to external or endogenous antigens. In the present study, it was confirmed that MAG (myelin-associated glycoprotein) antibodies (IgG, IgG4, and IgM) were detected by immunofluorescence (IFA) in serum of the patients with IgG4-RD. In vivo, the levels of prolactin and Th2 cytokines in CGRP+/- rats were higher than those in wild-type. Our findings indicate that the presence of CGRP-deficiency-mediated MAG antibodies is a probable molecular basis for the initial events which were triggered in IgG4-RD immune responses via prolactin upregulation.

4.
Brain Imaging Behav ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047237

RESUMO

Amyotrophic lateral sclerosis (ALS) is a multi-system disease featured by movement disorder. Studies on ALS using static neuroimaging indexes demonstrated inconsistent results. However, recent work indicated that the intrinsic brain activity was time-varying, and the abnormal temporal dynamics of brain activity in ALS remains unknown. Resting-state functional magnetic resonance imaging data were first obtained from 54 patients with ALS and 54 healthy controls (HCs). Then the dynamic regional homogeneity (d-ReHo) was calculated and compared between the two groups. Correlation analyses between altered d-ReHo and clinical scores were further performed. Compared with HCs, ALS patients showed higher d-ReHo in the left lingual gyrus while lower d-ReHo in the left rectus gyrus and left parahippocampal gyrus. Moreover, the d-ReHo in the left lingual gyrus exhibited correlation with disease progression rate in ALS at a trend level. Our findings suggested that altered dynamics in intrinsic brain activity might be a potential biomarker for diagnosing of ALS.

5.
J Cell Mol Med ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047847

RESUMO

Viral myocarditis (VMC) commonly triggers heart failure, for which no specific treatments are available. This study aims to explore the specific role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) in VMC. A VMC mouse model was induced by Coxsackievirus B3 (CVB3). Then, MEG3 and TNF receptor-associated factor 6 (TRAF6) were silenced and microRNA-223 (miR-223) was over-expressed in the VMC mice, followed by determination of ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Dual-luciferase reporter assay was introduced to test the interaction among MEG3, TRAF6 and miR-223. Macrophages were isolated from cardiac tissues and bone marrow, and polarization of M1 or M2 macrophages was induced. Then, the expressions of components of NLRP3 inflammatory body (NLRP3, ASC, Caspase-1), M1 markers (CD86, iNOS and TNF-α) and M2 markers (CD206, Arginase-1 and Fizz-1) were measured following MEG3 silencing. In the VMC mouse model, MEG3 and TRAF6 levels were obviously increased, while miR-223 expression was significantly reduced. Down-regulation of MEG3 resulted in the inhibition of TRAF6 by promoting miR-223. TRAF6 was negatively correlated with miR-223, but positively correlated with MEG3 expression. Down-regulations of MEG3 or TRAF6 or up-regulation of miR-223 was observed to increase mouse weight, survival rate, LVEF and LVFS, while inhibiting myocarditis and inflammation via the NF-κB pathway inactivation in VMC mice. Down-regulation of MEG3 decreased M1 macrophage polarization and elevated M2 macrophage polarization by up-regulating miR-223. Collectively, down-regulation of MEG3 leads to the inhibition of inflammation and induces M2 macrophage polarization via miR-223/TRAF6/NF-κB axis, thus alleviating VMC.

6.
Endocrine ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011881

RESUMO

PURPOSE: Ultrasound (US) is the most important imaging in the preoperative diagnosis of medullary thyroid carcinoma (MTC). MTC are easy to be misdiagnosed due to lacking typical malignant US features. This study investigated US features, clinical characteristics, prognosis, and detection methods, aimed to explore the association between US features and biological behavior, and improve early diagnosis of MTC. METHODS: A total of 189 MTC patients were enrolled in the study. Based on US features, 29 MTC were categorized as "indeterminate" (i-MTC) and 160 MTC were categorized as "malignant" (m-MTC) according to Thyroid Imaging, Reporting and Data System published by America College of Radiology (ACR TI-RADS). We compared US features, clinical characteristics and prognosis between both groups. We analyzed cytological categories of fine needle aspiration (FNA) within each i-MTC and m-MTC group according to the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We assessed the positive rate of FNA, frozen pathological examination, and preoperative serum calcitonin (Ctn) level in i-MTC and m-MTC groups. RESULTS: Preoperative US features were significantly different in shape, margin, composition, echogenicity, and calcifications between i-MTC and m-MTC (p < 0.05). I-MTC showed a hypoechoic solid or solid-cystic nodule lacking malignant US features. While m-MTC was presented as a solid nodule with obviously malignant US features. There were significant differences in lymph node dissection, extent of tumor, lymph node metastasis, and TNM stage and prognosis between i-MTC and m-MTC (p < 0.05). Compared to m-MTC, i-MTC underwent central neck dissection more frequently rather than lateral neck dissection at the time of the initial operation; i-MTC had less extrathyroidal invasion and lymph node metastasis, earlier stage, higher rate of biochemical cure, and lower rate of structural persistence/recurrence (p < 0.05). The 2017 TBSRTC of i-MTC and m-MTC was significantly different (p < 0.05). Preoperative serum Ctn level had a higher diagnostic sensitivity for both i-MTC and m-MTC when comparing to FNA and frozen pathological examination (p < 0.05). CONCLUSIONS: US features were associated with biological characteristics and prognosis of MTC. I-MTC lack malignant US features, preformed less aggressiveness, and better prognosis. TBSRTC according to FNA combined with serum Ctn were helpful for the detection of i-MTC.

7.
Inflammation ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33029757

RESUMO

Sepsis is an inflammatory disease characterized by dysregulation of inflammation. Macrophage-mediated inflammation has been implicated in the pathophysiology of sepsis. Itaconate is a metabolite produced in activated macrophages which has anti-inflammatory activities. In the present study, we investigated the potential effects of a cell-permeable itaconate derivative dimethyl itaconate on inflammation in sepsis. We established a lipopolysaccharide (LPS)-induced septic mouse model and administered dimethyl itaconate to the septic mice. The survival rate, serum level of pro-inflammatory cytokines, and lung pathology were evaluated. We also administered dimethyl itaconate to LPS-treated bone marrow-derived macrophages (BMDMs), and measured the cytokine production and Nrf2 expression. We also evaluated the effects of dimethyl itaconate on Nrf2-deficient mice. Administration of dimethyl itaconate enhanced survival rate, decreased serum level of TNF-α and IL-6, and ameliorated lung injury in septic mice. Dimethyl itaconate also suppressed LPS-induced production of TNF-α, IL-6, and NOS2 in BMDMs. Dimethyl itaconate activated Nrf2 and promoted the expression of Nrf2 and its downstream factor HO-1 and NQO-1. The regulatory activities of dimethyl itaconate on inflammatory cytokine production, mouse survival rate were abolished in septic Nrf2-/- mice. Dimethyl itaconate suppressed the inflammatory responses of macrophages in sepsis.

8.
Respir Med ; 173: 106159, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33010731

RESUMO

BACKGROUND: The outbreak of COVID-19 caused by SARS-CoV-2 has been a pandemic. The objective of our study was to explore the association between sex and clinical outcomes in patients with COVID-19. METHODS: Detailed clinical data including clinical characteristics, laboratory tests, imaging features and treatments of 1190 cases of adult patients with confirmed COVID-19 were retrospectively analyzed. Associations between sex and clinical outcomes were identified by multivariable Cox regression analysis. RESULTS: There were 635 (53.4%) male and 555 (46.6%) female patients in this study. Higher rates of acute kidney injury (5.5% vs. 2.9%, p = 0.026), acute cardiac injury (9.1% vs. 4.3%, p = 0.001), and disseminated intravascular coagulation (2.5% vs. 0.7%, P = 0.024) were observed in males. Compared with female patients, male patients with COVID-19 had a higher inhospital mortality rate (15.7% vs. 10.3%, p = 0.005). However, Cox regression analysis showed that sex did not influence inhospital mortality of COVID-19 patients. CONCLUSIONS: Male sex was associated with a worse prognosis of COVID-19, but it seems not to be an independent prognostic factor.

9.
Theranostics ; 10(24): 11144-11158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042275

RESUMO

Rationale: Radioresistance remains the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. This study aimed to investigate the role and regulatory mechanism of Cyclin K in lung cancer radioresistance. Methods: Expression levels of Cyclin K were measured by immunohistochemistry in human lung cancer tissues and adjacent normal lung tissues. Cell growth and proliferation, neutral comet and foci formation assays, G2/M checkpoint and a xenograft mouse model were used for functional analyses. Gene expression was examined by RNA sequencing and quantitative real-time PCR. Protein-protein interaction was assessed by immunoprecipitation and GST pull-down assays. Results: We report that Cyclin K is frequently overexpressed and correlates with poor prognosis in lung cancer patients. Functionally, we demonstrate that Cyclin K depletion results in reduced proliferation, defective G2/M checkpoint and enhanced radiosensitivity in lung cancer. Mechanistically, we reveal that Cyclin K interacts with and promotes the stabilization of ß-catenin protein, thereby upregulating the expression of Cyclin D1. More importantly, we show that Cyclin D1 is the major effector that mediates the biological functions of Cyclin K in lung cancer. Conclusions: These findings suggest that Cyclin K positively modulates the ß-catenin/Cyclin D1 axis to promote tumorigenesis and radioresistance in lung cancer, indicating that Cyclin K may represent a novel attractive biomarker for lung cancer radiotherapy.

10.
J Clean Prod ; : 124497, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33024356

RESUMO

The demand for eco-friendly poly (lactic acid) (PLA) nonwovens grows at a high rate in the past several decades, however, only a little attention has been received for flame retardant PLA nonwoven fabrics. In this work, a novel halogen-free self-intumescent polyelectrolyte tris (hydroxymethyl)-aminomethane polyphosphate (APTris) was synthesized by reacting ammonium polyphosphate with tris (hydroxymethyl) aminomethane, and was then used to improve the fire resistance of PLA nonwovens via a dip-nip process. The flammability characterization indicated the limiting oxygen index value was increased to 30.0% from 18.3%, and the damaged area in the vertical burning test was reduced by about 87.0% by the presence of APTris. The cone calorimeter test results revealed that the peak heat release rate and total heat release of the treated sample were decreased by 41.0% and 28.2% respectively compared with that of the control PLA nonwoven sample. The char residue was increased to 12.3 from 1.7 wt. % at 800 °C. It is suggested that the dense char barrier formed at the presence of APTris prevents heat, smoke, and gas transfer, and hence enhance thermal dilatability and flame retardancy of PLA nonwovens. This simple sustainable halogen-free treatment has great potential to produce cleaner commercialized flame-retardant PLA nonwovens.

11.
Aging (Albany NY) ; 122020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031059

RESUMO

In atherosclerosis, upregulated TILRR (FREM1 isoform 2) expression increases immune cell infiltration. We hypothesized that TILRR expression is also correlated with cancer progression. By analyzing data from Oncomine and the Tumor Immune Estimation Resource, we found that TILRR mRNA expression was significantly lower in breast cancer tissue than adjacent normal tissue. Kaplan-Meier survival analysis and immunohistochemical staining revealed shortened overall survival and disease-free survival in patients with low TILRR expression. TILRR transcript expression was positively correlated with immune score, immune cell biomarkers and the expression of CXCL10 and CXCL11. TILRR expression was also positively correlated with CD8+ and CD4+ T-cell infiltration. These correlations were verified using the ESTIMATE algorithm, gene set enrichment analysis and Q-PCR. We concluded that impaired TILRR expression is correlated with breast cancer prognosis and immune cell infiltration.

12.
Theranostics ; 10(25): 11595-11606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052235

RESUMO

Background: The oral microbiome may play an important role in colorectal carcinogenesis. However, few studies have investigated the association between oral microbiome and the development of colorectal cancer (CRC). We aimed to investigate whether oral health-colorectal tumor association has an underlying microbial basis, in the quest for novel non-invasive biomarkers for CRC. Methods: We collected oral swab samples from 161 patients with CRC, 34 patients with colorectal adenoma (CRA), and 58 healthy volunteers. The oral microbiota was assessed using 16S rRNA sequencing. We characterized oral microbiome, identified microbial markers, constructed and validated colorectal tumor (CRA and CRC) classifier. Results: Oral microbial composition and diversity were significantly different among the three groups, and the CRA group had the highest diversity. Analysis of the functional potential of oral microbiota demonstrated that the pathway involving cell motility was overrepresented in the CRA and CRC groups relative to that in the healthy controls. Moreover, a random forest model was constructed based on oral microbial markers, which could distinguish the colorectal tumor groups from the healthy controls and achieve a powerful classification potential in the discovery and validation cohorts. Conclusion: This study suggests a potential association between oral microbiome dysbiosis and colorectal cancer. Oral microbiota-based biomarkers may be helpful in predicting the risks for the development of CRA and CRC.

13.
Int J Med Sci ; 17(14): 2077-2086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922168

RESUMO

Background: Sepsis, as a clinical emergency, usually causes multiorgan dysfunction and can lead to high mortality. Establishment of specific and sensitive biomarkers for early diagnosis is critical to identify patients who would benefit from targeted therapy. In this study, we investigated this syndrome by analyzing the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with sepsis and identified sepsis-specific biomarkers. Methods: In this study, a total of 87 patients with sepsis and 40 healthy controls from a prospective multicenter cohort were enrolled. Samples from 44 subjects (24 patients with sepsis and 20 healthy controls) were sequenced and the remaining patients were included in the validation group. Using high-throughput sequencing, a gene expression profile of PBMCs from patients with sepsis was generated to elucidate the pathophysiology of sepsis and identify sepsis-specific biomarkers. Results: Principal component analysis (PCA) and unsupervised hierarchical cluster analysis showed that patients with sepsis separated from healthy controls. A total of 1639 differentially expressed genes (DEGs) were identified (|log2 fold change|>2, adjusted P value <0.05) between these two groups, with 1278 (78.0%) upregulated and 361 (22.0%) downregulated in patients with sepsis. Gene Ontology (GO) analysis of the upregulated DEGs identified 194 GO terms that were clustered into 27 groups, and analysis of the downregulated DEGs identified 20 GO terms that were clustered into 4 groups. Four unique genes were identified that could be predictive of patients with sepsis. External validation of the four genes using quantitative real-time polymerase chain reaction (qRT-PCR) was consistent with the results of mRNA sequencing, revealing their potential in sepsis diagnosis. Conclusions: The transcriptome characteristics of PBMCs, which were significantly altered in sepsis patients, provide new insights into sepsis pathogenesis. The four identified gene expression changes differentiated patients with sepsis from healthy subjects, which could serve as a convenient tool contributing to sepsis diagnosis.

14.
Ecotoxicol Environ Saf ; 207: 111295, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32949930

RESUMO

Cadmium (Cd) easily accumulates in tobacco, which endangers public health through Cd exposure from smoking. However, its uptake, translocation, and distribution in tobacco plants during plant development or its response to biochar application are poorly understood. A pot experiment was conducted with tobacco (Yunyan 87) grown in soil severely contaminated with Cd (30 mg kg-1) amended with 0, 1, and 2% (w/w) tobacco stem-derived biochar (BC). The absorption and accumulation of Cd in all parts of the tobacco plants were most active from the rosette stage to the fast growing stage, during which approximately 90% of the Cd deposited in the tobacco leaves occurred, especially in the lower leaves. The Cd concentrations in most plant parts without added biochar decreased significantly by 52.61-78.30% due to the rapid increase in biomass (dilution effect), although the Cd concentration in the lower leaves increased by 48.89% (P < 0.05). However, with the slowdown of the growth rate of tobacco at the maturity stage, the proportion of Cd accumulation in roots and stems without biochar addition increased by 29.01%, resulting in an increased Cd concentration in roots and stems by 63.29-86.80% (P < 0.05). In the different growth stages, the application of biochar reduced the contents of DTPA-extractable and exchangeable Cd in the soil by 5.11-35.14% and 9.20-54.05%, respectively, thus reducing the absorption, accumulation and concentration of Cd in all parts of the tobacco plant. In addition, the inhibitive effect of biochar on the Cd concentration in the leaves was weak at the rosette stage (22.17-53.72%) compared with the other stages (46.14-78.88%), and the degree of inhibition of biochar on the Cd concentration in the middle leaves (37.94-59.24%) was lower than that in the upper and lower leaves (49.04-73.54%) at all developmental stages. However, the long-term remediation effect of biochar on soil Cd contamination needs to be further verified, and the combination of biochar and other technologies should receive additional attention.

15.
BMC Cancer ; 20(1): 823, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867707

RESUMO

BACKGROUND: We describe the clinical benefit of immune checkpoint inhibitors using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and ASCO VF. METHODS: We identify all approved indications of immune checkpoint inhibitors based on RCTs between January 1, 2011 and September 30, 2018 by FDA. Information including medians and HR of OS (PFS or DFS) and 95% CI, grade 3 or 4 toxicities in each arm, QOL data, survival probability at fixed time were extracted. RESULTS: Immune checkpoint inhibitors were approved for 18 indications based on RCTs. All the indications meet the ESMO-MCBS 1.1 threshold for meaningful benefit. By the updated ASCO-VF, the median Net Health Benefit (NHB) of these agents was 55.3 (range 17.4-77.1). Two third of the indication gained the bonus points for durable survival benefits by updated ASCO VF. When updated results were incorporated in the assessment, clinical benefit of most approved immune checkpoint inhibitors increased with a median improvement of NHB of 10 (range 2-20). CONCLUSIONS: Approved immune checkpoint inhibitors provided clinical meaningful benefit by ESMO-MCBS 1.1, and most of these agents reach the threshold for bonus points for durable survival in the updated ASCO VF.

16.
BMC Urol ; 20(1): 136, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867742

RESUMO

BACKGROUND: Calcium oxalate monohydrate (COM), the major crystalline composition of most kidney stones, induces inflammatory infiltration and injures in renal tubular cells. However, the mechanism of COM-induced toxic effects in renal tubular cells remain ambiguous. The present study aimed to investigate the potential changes in proteomic landscape of proximal renal tubular cells in response to the stimulation of COM crystals. METHODS: Clinical kidney stone samples were collected and characterized by a stone component analyzer. Three COM-enriched samples were applied to treat human proximal tubular epithelial cells HK-2. The proteomic landscape of COM-crystal treated HK-2 cells was screened by TMT-labeled quantitative proteomics analysis. The differentially expressed proteins (DEPs) were identified by pair-wise analysis. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEPs were performed. Protein interaction networks were identified by STRING database. RESULTS: The data of TMT-labeled quantitative proteomic analysis showed that a total of 1141 proteins were differentially expressed in HK-2 cells, of which 699 were up-regulated and 442 were down-regulated. Functional characterization by KEGG, along with GO enrichments, suggests that the DEPs are mainly involved in cellular components and cellular processes, including regulation of actin cytoskeleton, tight junction and focal adhesion. 3 high-degree hub nodes, CFL1, ACTN and MYH9 were identified by STRING analysis. CONCLUSION: These results suggested that calcium oxalate crystal has a significant effect on protein expression profile in human proximal renal tubular epithelial cells.

17.
PLoS One ; 15(9): e0238179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881902

RESUMO

Carotenoid cleavage dioxygenase (CCD), a key enzyme in carotenoid metabolism, cleaves carotenoids to form apo-carotenoids, which play a major role in plant growth and stress responses. CCD genes had not previously been systematically characterized in Brassica napus (rapeseed), an important oil crop worldwide. In this study, we identified 30 BnCCD genes and classified them into nine subgroups based on a phylogenetic analysis. We identified the chromosomal locations, gene structures, and cis-promoter elements of each of these genes and performed a selection pressure analysis to identify residues under selection. Furthermore, we determined the subcellular localization, physicochemical properties, and conserved protein motifs of the encoded proteins. All the CCD proteins contained a retinal pigment epithelial membrane protein (RPE65) domain. qRT-PCR analysis of expression of 20 representative BnCCD genes in 16 tissues of the B. napus cultivar Zhong Shuang 11 ('ZS11') revealed that members of the BnCCD gene family possess a broad range of expression patterns. This work lays the foundation for functional studies of the BnCCD gene family.

18.
PLoS Negl Trop Dis ; 14(8): e0008660, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866199

RESUMO

Aedes mosquitoes can transmit dengue and several other severe vector-borne viral diseases, thereby influencing millions of people worldwide. Insects primarily control and clear the viral infections via their innate immune systems. Mitogen-Activated Protein Kinases (MAPKs) and antimicrobial peptides (AMPs) are both evolutionarily conserved components of the innate immune systems. In this study, we investigated the role of MAPKs in Aedes mosquitoes following DENV infection by using genetic and pharmacological approaches. We demonstrated that knockdown of ERK, but not of JNK or p38, significantly enhances the viral replication in Aedes mosquito cells. The Ras/ERK signaling is activated in both the cells and midguts of Aedes mosquitoes following DENV infection, and thus plays a role in restricting the viral infection, as both genetic and pharmacological activation of the Ras/ERK pathway significantly decreases the viral titers. In contrast, inhibition of the Ras/ERK pathway enhances DENV infection. In addition, we identified a signaling crosstalk between the Ras/ERK pathway and DENV-induced AMPs in which defensin C participates in restricting DENV infection in Aedes mosquitoes. Our results reveal that the Ras/ERK signaling pathway couples AMPs to mediate the resistance of Aedes mosquitoes to DENV infection, which provides a new insight into understanding the crosstalk between MAPKs and AMPs in the innate immunity of mosquito vectors during the viral infection.


Assuntos
Aedes/virologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Vírus da Dengue/imunologia , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Linhagem Celular , Sistema Digestório/virologia , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Imunidade Inata , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mosquitos Vetores/virologia , Carga Viral , Replicação Viral/efeitos dos fármacos
19.
Cell Death Differ ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901121

RESUMO

UBE2O, an E2/E3 hybrid ubiquitin-protein ligase, has been implicated in the regulation of adipogenesis, erythroid differentiation, and tumor proliferation. However, its role in cancer radioresistance remains completely unknown. Here, we uncover that UBE2O interacts and targets Mxi1 for ubiquitination and degradation at the K46 residue. Furthermore, we show that genetical or pharmacological blockade of UBE2O impairs tumor progression and radioresistance in lung cancer in vitro and in vivo, and these effects can be restored by Mxi1 inhibition. Moreover, we demonstrate that UBE2O is overexpressed and negatively correlated with Mxi1 protein levels in lung cancer tissues. Collectively, our work reveals that UBE2O facilitates tumorigenesis and radioresistance by promoting Mxi1 ubiquitination and degradation, suggesting that UBE2O is an attractive radiosensitization target for the treatment of lung cancer.

20.
Phys Chem Chem Phys ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914819

RESUMO

Sodium-ion batteries (SIBs) have attracted tremendous attention as potential low-cost energy storage alternatives to lithium-ion batteries (LIBs) due to the intrinsic safety and great abundance of sodium. For developing competitive SIBs, highly efficient anode materials with large capacity and rapid ion diffusion are indispensable. In this study, a two-dimensional (2D) Dirac monolayer, that is, borophosphene, is proposed as a promising anode material for high performance SIBs on the basis of density functional theory calculations. The performances of Na adsorption and diffusion, maximum specific capacity, open circuit voltage, cyclical stability and electronic properties combined with Bader charge analysis are explored. It is found that borophosphene can spontaneously adsorb a Na atom with a binding energy of -0.838 eV. A low diffusion energy barrier of 0.221 eV suggests rapid ion conductivity. More intriguingly, a maximum specific capacity of 1282 mA h g-1 can be achieved in borophosphene, which is one of the largest values reported for 2D anode materials for SIBs. A low average voltage of 0.367 V is estimated, implying a suitable operating voltage of the anode material. The metallic properties, tiny surface expansion, and good kinetic stability of sodiated borophosphene give rise to high electrical conductivity and favorable cyclability. These abovementioned advantages suggest that borophosphene can be used as a Dirac anode material for SIBs with excellent performance including a large specific capacity, high-rate capability, and favorable cyclability.

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