Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 319
Filtrar
1.
Ultramicroscopy ; 213: 112992, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32387681

RESUMO

In an atomic force microscope (AFM) system, the measurement accuracy in the scan images is determined by the displacement accuracy of piezo scanner. The hysteresis model of piezo scanner displacement is complex and difficult to correct, which is the main reason why the output displacement of the piezo scanner does not have high precision. In this study, an image pixel hysteresis model of the piezo scanner displacement in the AFM system was established. An AFM was used to scan a two-dimensional (2D) grating in the 0 ° and 90 ° directions and a polynomial fitting method was employed to obtain the image pixel hysteresis model parameters of the piezo scanner displacement in the X-direction and Y-direction. The image pixel hysteresis model was applied to correct the AFM scan image of regular octagons. The results showed that the relative measurement error in the X-direction was decreased from 12.47% to 0.52% after the correction and that in the Y-direction decreased from 28.57% to 0.35%. The image pixel hysteresis model can be applied in the post-processing software of a commercial AFM system. The model solves the hysteresis problem of the AFM system and improves the measuring accuracy of AFM in 2 degrees of freedom (2 DOF).

2.
Vet Med Sci ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419393

RESUMO

Porcine deltacoronavirus (PDCoV) has been detected sporadically in China since its first description in 2012. In our study, 62 faecal and intestinal samples from pigs with diarrhoea were collected in Guangxi Province, China, during 2017 and 2018. Twelve samples (19.4%, 12/62) were positive for PDCoV. Five complete genomes of PDCoV were then determined, and sequence alignment revealed that the five strains had discontinuous deletions at 400-401 aa in non-structural protein 2 (NSP2) and 758-760 aa in non-structural protein 3 (NSP3) compared with the respective proteins in the HKU15-44 strain. Notably, the CHN-GX81-2018 strain contained two insertions in the S gene and 3'-UTR. Multiple sequence alignment and phylogenetic analysis showed that four strains shared 98.2%-98.4% nucleotide identity with CHN-AH-2004 and were classified into a new cluster of China lineage strains, whereas the CHN-GX81-2018 strain shared 98.7% nucleotide identity with Vietnam/Binh21/2015 and belonged to the Vietnam/Laos/Thailand lineage. Recombination analyses revealed that four strains were the result of recombination between CHN-HB-2014 and Vietnam/Binh21/2015 strains. This study demonstrated the co-existence of multiple lineages of PDCoV in China, and our findings will aid the reorganization and evolution of the virus.

3.
J Clin Pharm Ther ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415722

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Thyroid follicular carcinoma is a malignant tumor from thyroid follicular epithelium, which is prone to involve capsular and vascular invasion. The present study was conducted in order to detect the expression of microRNA-155-5p (miR-155-5p) in thyroid follicular carcinoma with an attempt to analyze its involvement in apoptosis-related factors. METHODS: Forty-five patients with thyroid follicular carcinoma made up the observation group and 45 patients with thyroid follicular adenoma were included into the control group. Tissues of thyroid follicular carcinoma and thyroid follicular adenoma were obtained from the patients, and analysed for expression of miR-155-5p by real-time fluorescence quantitative PCR (qPCR). The expression of cysteine-containing aspartic acid protein hydrolase-3 (Caspase-3) in thyroid follicular carcinoma was detected with the use of Western Blot analyses. Immunohistochemical method was used to detect the expression of B-cell lymphoma protein-2 (Bcl-2) in thyroid follicular carcinoma. RESULTS: There was significant difference in the expression of miR-155-5p between the two groups (Observation vs Control: 1.46 ± 0.42 vs 0.98 ± 0.33 P < .05). The expression of miR-155-5p was significantly different in the maximum diameter of tumor, vascular invasion and neural invasion (maximum diameter of tumor <4 cm vs ≥4 cm: 1.36 ± 0.40 vs 1.68 ± 0.32, vascular invasion N vs Y: 1.35 ± 0.42 vs 1.69 ± 0.39, Neural invasion N vs Y: 1.35 ± 0.38 vs 1.70 ± 0.31 P < .05). However, there was no significant difference in the expression of miR-155-5p in terms of different gender, age and group with or without lymph node metastasis (P > .05). Based on survival analysis, patients with high expression of miR-155-5p experienced short survival time (median survival time was 45 months, P < .05). There was a negative correlation between miR-155-5p and Caspase-3 (r = -.50, P < .05). In addition, positive correlation was observed between miR-155-5p and Bcl-2 (r = .55, P < .05). WHAT IS NEW AND CONCLUSION: There was increased expression of miR-155-5p in thyroid follicular carcinoma. The abnormal expression of miR-155-5p may be an independent prognostic factor for thyroid follicular carcinoma associated with cell apoptosis.

4.
Zhongguo Zhong Yao Za Zhi ; 45(4): 861-877, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237487

RESUMO

To qualitatively characterize the chemical composition of Guizhi Fuling Capsules using UPLC-ESI-Q-TOF-MS/MS. The analysis was performed on Agilent ZORBAX RRHD Eclipes Plus C_(18)(2.1 mm×100 mm, 1.8 µm) column,that was eluted with mobile phase consisting of acetonitrile and 0.1% formic acid in a gradient mode. The flow rate was 0.4 mL·min~(-1), and column temperature was 30 ℃. Tandem mass spectrometry was acquired in both negative and positive ESI modes. These components were further analyzed based on high-resolution mass-to-charge ratios, fragment ion species, reference substances and literature data. In conclusion, a total of 200 compounds were identified, in which 40 were verified with reference substances. The current study laid a foundation for in-depth studies of its mass balance and pharmacodynamics.

5.
J Econ Entomol ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32300789

RESUMO

Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), is a high-risk invasive forest pest worldwide. We surveyed Asian longhorned beetle parasitoid guilds and their seasonal abundance using field-deployed sentinel host logs infested with Asian longhorned beetle eggs or newly hatched (early-instar) larvae in three different sites of China (Beijing City, Shanghai City, and Jilin Province) from 2015 to 2018. Our survey detected 12 species of hymenopteran parasitoids (four Pteromalidae, three Braconidae, two Eupelmidae, one Eurytomidae, one Ichneumonidae, and one Bethylidae) attacking sentinel Asian longhorned beetle larvae or eggs deployed in these sites. Total parasitism by all the parasitoid species varied with different sites and across different years of the survey (averaging 7-16% in Beijing, 4-11% in Shanghai, and 0-0.2% in Jilin Province). In addition, the seasonal pattern of parasitism also differed among different sites, with parasitism peaking in July in the northern site (Beijing, 19%) and June in the southern site (Shanghai, 16%). Among all the parasitoid species recovered, Oxysychus sp. (Hymenoptera: Pteromalidae) was the most abundant parasitoid species in both Beijing and Shanghai (with 42-66% relative abundance and an average of 6% Asian longhorned beetle parasitism). The second most abundant species was Bracon planitibiae Yang, Cao et Gould (Hymenoptera: Braconidae), which accounted for 35% of the species collected and caused an average of 5% Asian longhorned beetle parasitism. Relevance of our findings to Asian longhorned beetle biocontrol is discussed.

6.
Small ; : e1905853, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249535

RESUMO

The exploration of materials with reversible and stable electrochemical performance is crucial in energy storage, which can (de) intercalate all the alkali-metal ions (Li+ , Na+ , and K+ ). Although transition-metal chalcogenides are investigated continually, the design and controllable preparation of hierarchical nanostructure and subtle composite withstable properties are still great challenges. Herein, component-optimal Co0.85 Se1- x Sx nanoparticles are fabricated by in situ sulfidization of metal organic framework, which are wrapped by the S-doped graphene, constructing a hollow polyhedron framework with double carbon shells (CoSSe@C/G). Benefiting from the synergistic effect of composition regulation and architecture design by S-substitution, the electrochemical kinetic is enhanced by the boosted electrochemistry-active sites, and the volume variation is mitigated by the designed structure, resulting in the advanced alkali-ion storage performance. Thus, it delivers an outstanding reversible capacity of 636.2 mAh g-1 at 2 A g-1 after 1400 cycles for Li-ion batteries. Remarkably, satisfactory initial charge capacities of 548.1 and 532.9 mAh g-1 at 0.1 A g-1 can be obtained for Na-ion and K-ion batteries, respectively. The prominent performance combined with the theory calculation confirms that the synergistic strategy can improve the alkali-ion transportation and structure stability, providing an instructive guide for designing high-performance anode materials for universal alkali-ion storage.

7.
J Colloid Interface Sci ; 573: 223-231, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32278953

RESUMO

Structure control is widely admitted as a feasible strategy to restrain volume change and enhance electrical conductivity for chalcogenide anode materials. Herein, three-dimensionally hierarchical structure Co0.85Se@N-doped graphene hybrid is well-designed and synthesized by a facile hydrothermal strategy and post-calcination. It is noted that, owing to the nanoscale Kirkendall effect, the Co0.85Se nanograins derived from uniform zeolitic imidazolate framework (ZIF-67) precursor are incorporated into a polyhedron-in-polyhedron structure, which is consisted of in-situ formed amorphous carbon and interconnected pliable graphene nanosheets with enormous N-doping atoms. This unique dual-carbon protecting layers are beneficial to mitigate the volume expansion with high integrity, and facilitate the fast Li/electron transport with improved conductivity simultaneously, thus resulting in the superior Li-storage performance. As expected, the framework-controlled Co0.85Se@N-doped rGO composite demonstrates an outstanding cycling stability (787.7 mA h g-1 after 1000 cycles at 2 A g-1) and remarkable rate capability (400.8 mA h g-1 at ultrahigh rate of 10 A g-1). This work presents an enlightened strategy to design chalcogenide anode with desired nano-/microstructure by structure control and kinetic increase.

8.
iScience ; 23(4): 101003, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32278286

RESUMO

Selective linkage of renewable alcohols and ammonia into functional products would not only eliminate the prepreparation steps to generate active amino agents but also help in the conservation of our finite fossil carbon resources and contribute to the reduction of CO2 emission. Herein the development of a novel 2-(4-methoxyphenyl)-1,8-naphthyridine-based iridium (III) complex is reported, which exhibits excellent catalytic performance toward a new hydrogen transfer-mediated annulation reaction of 2-nitrobenzylic alcohols with alcohols and ammonia. The catalytic transformation proceeds with the striking features of good substrate and functional group compatibility, high step and atom efficiency, no need for additional reductants, and liberation of H2O as the sole by-product, which endows a new platform for direct access to valuable quinazolines. Mechanistic investigations suggest that the non-coordinated N-atom in the ligand serves as a side arm to significantly promote the condensation process by hydrogen bonding.

9.
PLoS Pathog ; 16(4): e1008443, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32343740

RESUMO

Staphylococcus aureus (SA) is the causative agent of both skin/soft tissue infections as well as invasive bloodstream infections. Though vaccines have been developed to target both humoral and T cell-mediated immune responses against SA, they have largely failed due to lack of protective efficacy. Group 1 CD1-restricted T cells recognize lipid rather than peptide antigens. Previously found to recognize lipids derived from cell wall of Mycobacterium tuberculosis (Mtb), these cells were associated with protection against Mtb infection in humans. Using a transgenic mouse model expressing human group 1 CD1 molecules (hCD1Tg), we demonstrate that group 1 CD1-restricted T cells can recognize SA-derived lipids in both immunization and infection settings. Systemic infection of hCD1Tg mice showed that SA-specific group 1 CD1-restricted T cell response peaked at 10 days post-infection, and hCD1Tg mice displayed significantly decreased kidney pathology at this time point compared with WT control mice. Immunodominant SA lipid antigens recognized by group 1 CD1-restricted T cells were comprised mainly of cardiolipin and phosphatidyl glycerol, with little contribution from lysyl-phosphatidyl glycerol which is a unique bacterial lipid not present in mammals. Group 1 CD1-restricted T cell lines specific for SA lipids also conferred protection against SA infection in the kidney after adoptive transfer. They were further able to effectively control SA replication in vitro through direct antigen presentation by group 1 CD1-expressing BMDCs. Together, our data demonstrate a previously unknown role for group 1 CD1-restricted SA lipid-specific T cells in the control of systemic MRSA infection.

10.
Mol Cancer ; 19(1): 59, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171295

RESUMO

Following the publication of article [1], the authors found that the images of Transwell Matrigel invasion (Fig. 7d) are incorrect.

11.
ACS Nano ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32134632

RESUMO

Constructing a heterojunction and introducing an interfacial interaction by designing ideal structures have the inherent advantages of optimizing electronic structures and macroscopic mechanical properties. An exquisite hierarchical heterogeneous structure of bimetal sulfide Sb2S3@FeS2 hollow nanorods embedded into a nitrogen-doped carbon matrix is fabricated by a concise two-step solvothermal method. The FeS2 interlayer expands in situ grow on the interface of hollow Sb2S3 nanorods within the nitrogen-doped graphene matrix, forming a delicate heterostructure. Such a well-designed architecture affords rapid Na+ diffusion and improves charge transfer at the heterointerfaces. Meanwhile, the strongly synergistic coupling interaction among the interior Sb2S3, interlayer FeS2, and external nitrogen-doped carbon matrix creates a stable nanostructure, which extremely accelerates the electronic/ion transport and effectively alleviates the volume expansion upon long cyclic performance. As a result, the composite, as an anode material for sodium-ion batteries, exhibits a superior rate capability of 537.9 mAh g-1 at 10 A g-1 and excellent cyclic stability with 85.7% capacity retention after 1000 cycles at 5 A g-1. Based on the DFT calculation, the existing constructing heterojunction in this composite can not only optimize the electronic structure to enhance the conductivity but also favor the Na2S adsorption energy to accelerate the reaction kinetics. The outstanding electrochemical performance sheds light on the strategy by the rational design of hierarchical heterogeneous nanostructures for energy storage applications.

12.
Phytochemistry ; 173: 112223, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32113063

RESUMO

Seven undescribed labdane diterpenoids, japonicones A-G, were isolated from the aerial parts of Leonurus japonicus Houtt. Japonicones C-G contained two keto carbonyl groups in their structures attached to C-3 and C-7, which are rare for labdane diterpenoids. The structures and absolute configurations of japonicones A-G were established by means of spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ECD). Their anti-inflammatory activities were evaluated by measuring their inhibitory effects on PGE2 production in LPS-stimulated RAW264.7 macrophages. Japonicones A-D and G showed inhibition of PGE2 production with IC50 values in the range of 8.62-30.71 µM (the positive control paracetamol showed an IC50 = 5.79 µM).


Assuntos
Diterpenos , Leonurus , Anti-Inflamatórios , Espectroscopia de Ressonância Magnética , Estrutura Molecular
13.
Inflammation ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152924

RESUMO

Acute lung injury (ALI) is a kind of lung serious disease which leads to the damage of alveolar epithelial cells and capillary endothelial. Lipopolysaccharide (LPS) is one of the common factors inducing ALI. The previous study has reported that the anti-inflammatory effect of peiminine, but little is known about its effect on the ALI induced by LPS. The aim of this study is to investigate the therapeutic effect of peiminine on LPS-induced acute lung injury and potential mechanisms. Mice were given LPS through nasal cavity to establish ALI model, and then the peiminine (1, 3, or 5 mg/kg) was injected into the mice as the experimental group. In the present study, we would measure the W/D ratio, activity of MPO, the histopathological changes, and the levels of cytokines. The results showed that peiminine could reduce the W/D ratio and the MPO activity significantly. Furthermore, the histopathological changes and the expression of TNF-α, IL-1ß, and IL-6 were inhibited after the peiminine treatment. In vitro, peiminine significantly inhibited LPS-induced IL-8 production in A549 lung epithelial cells. Meanwhile, the activity of NF-κB signaling pathway was suppressed obviously by peiminine with the western blot analysis. Also, peiminine significantly attenuated LPS-induced AKT and PI3K phosphorylation. In addition, peiminine was found to disrupt lipid rafts formation by attenuating the cholesterol content. In conclusion, peiminine could attenuate LPS-induced ALI in mice and it may become a new approach to treat ALI.

14.
Infect Genet Evol ; 82: 104286, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32171841

RESUMO

Bufavirus (BuV) can infect a variety of hosts, including human, bats, rats, dog, swine and shrew species and are suggested related to diarrhea disease. Porcine bufaviruses (PoBuV) were first detected in Hungarian pig farms in 2016. To determine the prevalence and genetic diversity of PoBuV in China, we developed SYBR Green-based real-time PCR assays to detect PoBuV in Guangxi pigs. Real-time PCR detected PoBuV in 30 (29.13%, 30/103) of the samples with diarrhoeal intestinal tissues and rectal swabs. PoBuV-positive intestinal tissues and rectal swabs samples, co-infection with PEDV (15/30, 50.0%), followed by PDCoV (8/30, 26.67%), PoRV (6/30, 20.0%), PRRSV (5/30, 16.67%), and PCV2 (3/30, 10.0%) were observed. Fourteen complete genomes were cloned and sequenced. The results showed that they were 4189 bp in length and combined three open reading frames (ORFs) in the order 5'-NS1-VP1/VP2-3'. Fourteen strains shared 96.5%-99.8% identity among themselves and 92.7%-97.9% with the PoBuV reference sequences. Phylogenetic analysis based on the deduced amino acid sequence of the VP2 gene showed fourteen strains belonging to PoBuV and were grouped into the three branches. These results help to provide new insight into the molecular epidemiology of PoBuV in the world.

15.
Metab Brain Dis ; 35(5): 793-807, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215835

RESUMO

Inflammatory demyelination in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Besides MS disease-modifying therapy, targeting myelin sheath protection/regeneration is currently a hot spot in the treatment of MS. Here, we attempt to explore the therapeutic potential of Bilobalide (BB) for the myelin protection/regeneration in EAE model. The results showed that BB treatment effectively prevented worsening and demyelination of EAE, accompanied by the inhibition of neuroinflammation that should be closely related to T cell tolerance and M2 macrophages/microglia polarization. BB treatment substantially inhibited the infiltration of T cells and macrophages, thereby alleviating the enlargement of neuroinflammation and the apoptosis of oligodendrocytes in CNS. The accurate mechanism of BB action and the feasibility of clinical application in the prevention and treatment of demyelination remain to be further explored.

16.
Sci Total Environ ; 718: 137234, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32087580

RESUMO

Increasing atmospheric carbon dioxide has led to a decrease in the pH of the ocean, which influences the speciation of heavy metals and consequently affects metal toxicity in marine organisms. To investigate the effects of seawater acidification and metals on the antioxidant defenses of marine fishes, the flounder Paralichthys olivaceus, was continuously exposed to cadmium (Cd; control, 0.01 and 0.15 mg L-1) and acidified seawater (control (pH 8.10), 7.70 and 7.30) for 49 days from embryogenesis to settlement. The results demonstrated that both Cd and acidified seawater could induce oxidative stress and consequently cause lipid peroxidation (LPO) in the larvae. Antioxidants (i.e., superoxide dismutase, SOD; catalase, CAT; reduced glutathione, GSH; glutathione S-transferase, GST; glutathione peroxidase, GPx; and glutathione reductase, GR) functioned to defend the larvae against oxidative damage. Overall, Cd induced (SOD, GST and GSH) or inhibited (CAT and GPx) the enzymatic activities or contents of all the selected antioxidants except for GR. The antioxidants responded differently to seawater acidification, depending on their interaction with the metal. Similarly, the mRNA expressions of the antioxidant-related genes were upregulated (sod, gr and gst) or downregulated (cat and gpx) in response to increasing Cd exposure. Seawater acidification did not necessarily affect all of the biomarkers; in some cases (e.g., SOD and sod, GR and gr), Cd stress may have exceeded and masked the stress from seawater acidification in regulating the antioxidant defense of the larvae. The integrated biomarker response (IBR) was enhanced with increasing levels of the stressors. These findings support the hypothesis that seawater acidification not only directly affects the antioxidant defense in flounder larvae but also interacts with Cd to further regulate this defense. This study has ecological significance for assessing the long-term impacts of ocean acidification and metal pollution on the recruitment of fish populations in the wild.

17.
J Exp Med ; 217(5)2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32069354

RESUMO

The ubiquitin pathway has been shown to regulate iNKT cell immunity, but the deubiquitinase involved in this process has not been identified. Herein we found that ubiquitin-specific peptidase 22 (USP22) is highly expressed in iNKT cells during their early developmental stage 1. USP22 deficiency blocked the transition from stage 1 to 2 during iNKT cell development in a cell-intrinsic manner. USP22 suppression also diminishes iNKT17 and iNKT1 differentiation but favors iNKT2 polarization without altering conventional T cell activation and differentiation. USP22 interacts with the Mediator complex subunit 1 (MED1), a transcription coactivator involved in iNKT cell development. Interestingly, while interacting with MED1, USP22 does not function as a deubiquitinase to suppress MED1 ubiquitination for its stabilization. Instead, USP22 enhances MED1 functions for IL-2Rß and T-bet gene expression through deubiquitinating histone H2A but not H2B monoubiquitination. Therefore, our study revealed USP22-mediated histone H2A deubiquitination fine-tunes MED1 transcriptional activation as a previously unappreciated molecular mechanism to control iNKT development and functions.

18.
Virus Res ; 278: 197869, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31962065

RESUMO

Porcine deltacoronavirus (PDCoV) is the etiological agent of acute diarrhoea and vomiting in pigs, threatening the swine industry worldwide. Although several PDCoV studies have been conducted in China, more sequence information is needed to understand the molecular characterization of PDCoV. In this study, the partial ORF1a, spike protein (S) and nucleocapsid protein (N) were sequenced from Shandong Province between 2017 and 2018. The sequencing results for the S protein from 10 PDCoV strains showed 96.7 %-99.7 % nucleotide sequence identity with the China lineage strains, while sharing a lower level of nucleotide sequence identity, ranging from 95.7 to 96.8%, with the Vietnam/Laos/Thailand lineage strains. N protein sequencing analysis showed that these strains showed nucleotide homologies of 97.3%-99.3% with the reference strains. Phylogenetic analyses based on S protein sequences showed that these PDCoV strains were classified into the China lineage. The discontinuous 2 + 3 aa deletions at 400-401 and 758-760 were found in the Nsp2 and Nsp3 coding region in five strains, respectively, with similar deletions having been identified in Vietnam, Thailand, and Laos. Three novel patterns of deletion were observed for the first time in the Nsp2 and Nsp3 regions. Importantly, those findings suggest that PDCoV may have undergone a high degree of variation since PDCoV was first detected in China.

19.
Cardiovasc Res ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31995173

RESUMO

AIMS: Cardiac sympathetic overactivation is an important trigger of ventricular arrhythmias in patients with chronic heart failure (CHF). Our previous study demonstrated that N-type calcium (Cav2.2) currents in cardiac sympathetic postganglionic (CSP) neurons were increased in CHF. This study investigated the contribution of Cav2.2 channels in cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. METHODS AND RESULTS: Rat CHF was induced by surgical ligation of the left coronary artery. Lentiviral Cav2.2-α shRNA or scrambled shRNA was transfected in vivo into stellate ganglia (SG) in CHF rats. Final experiments were performed at 14 weeks after coronary artery ligation. Real-time PCR and Western blot data showed that in vivo transfection of Cav2.2-α shRNA reduced the expression of Cav2.2-α mRNA and protein in the SG in CHF rats. Cav2.2-α shRNA also reduced Cav2.2 currents and cell excitability of CSP neurons and attenuated cardiac sympathetic nerve activities (CSNA) in CHF rats. The power spectral analysis of heart rate variability (HRV) further revealed that transfection of Cav2.2-α shRNA in the SG normalized CHF-caused cardiac sympathetic overactivation in conscious rats. Twenty-four-hour continuous telemetry ECG recording revealed that this Cav2.2-α shRNA not only decreased incidence and duration of ventricular tachycardia/fibrillation (VT/VF), but also improved CHF-induced heterogeneity of ventricular electrical activity in conscious CHF rats. Cav2.2-α shRNA also decreased susceptibility to ventricular arrhythmias in anesthetized CHF rats. However, Cav2.2-α shRNA failed to improve CHF-induced cardiac contractile dysfunction. Scrambled shRNA did not affect Cav2.2 currents and cell excitability of CSP neurons, CSNA, HRV, and ventricular arrhythmogenesis in CHF rats. CONCLUSIONS: Overactivation of Cav2.2 channels in CSP neurons contributes to cardiac sympathetic hyperactivation and ventricular arrhythmogenesis in CHF. This suggests that discovering purely selective and potent small-molecule Cav2.2 channel blockers could be a potential therapeutic strategy to decrease fatal ventricular arrhythmias in CHF. TRANSLATIONAL PERSPECTIVES: Our present study demonstrates that inhibition of N-type Ca2+ channels in CSP neurons attenuates CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias. The clinical significance of this study is to open a new avenue in therapeutics working against lethal ventricular arrhythmias in patients with CHF. N-type Ca2+ channels in CSP neurons could be a new therapeutic target for cardiac sympathetic overactivation and ventricular arrhythmias in CHF. Exploring specific, small-molecule N-type Ca2+ channel blockers with local targeting drug delivery system could translate to clinical trials and applications that improve outcomes for patients with CHF.

20.
ACS Appl Mater Interfaces ; 12(2): 2708-2716, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31894693

RESUMO

Conjugated polymers are of high potential in the development of spintronic devices. In this paper, we report systematic studies on spin transport properties of a semiconducting polymer PBDTTT-C-T in the permalloy/polymer/Pt trilayer using the spin pumping method. Pure spin current with long spin relaxation time is observed via the inverse spin Hall effect (ISHE) measurements. Furthermore, spin current is also found to propagate through the blend film consisting of a small amount of PBDTTT-C-T in an insulating matrix. The polymer blend exhibits a remarkably enhanced spin relaxation length (56 nm) and carrier mobility compared to pristine PBDTTT-C-T. From film microstructural characterizations, we propose that the enhanced spin/carrier transport properties are attributed to the formation of interlinked nanonetwork comprising of the PBDTTT-C-T chain bundles in the inert matrix to afford efficient intrachain charge conduction pathway. Temperature- dependent ISHE measurements support the spin-orbit coupling dominated spin relaxation mechanism.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA