Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 109
Filtrar
1.
Mol Ther ; 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34400329

RESUMO

Heart failure is a leading cause of fatality in Duchenne muscular dystrophy (DMD) patients. Previously, we discovered that cardiac and skeletal-muscle-enriched CIP proteins play important roles in cardiac function. Here, we report that CIP, a striated muscle-specific protein, participates in the regulation of dystrophic cardiomyopathy. Using a mouse model of human DMD, we found that deletion of CIP leads to dilated cardiomyopathy and heart failure in young, non-syndromic mdx mice. Conversely, transgenic overexpression of CIP reduces pathological dystrophic cardiomyopathy in old, syndromic mdx mice. Genome-wide transcriptome analyses reveal that molecular pathways involving fibrogenesis and oxidative stress are affected in CIP-mediated dystrophic cardiomyopathy. Mechanistically, we found that CIP interacts with dystrophin and calcineurin (CnA) to suppress the CnA-Nuclear Factor of Activated T cells (NFAT) pathway, which results in decreased expression of Nox4, a key component of the oxidative stress pathway. Overexpression of Nox4 accelerates the development of dystrophic cardiomyopathy in mdx mice. Our study indicates CIP is a modifier of dystrophic cardiomyopathy and a potential therapeutic target for this devastating disease.

2.
Nat Commun ; 12(1): 5147, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446716

RESUMO

PTEN is frequently mutated in human cancers and PTEN mutants promote tumor progression and metastasis. PTEN mutations have been implicated in immune regulation, however, the underlying mechanism is largely unknown. Here, we report that PTENα, the isoform of PTEN, remains active in cancer bearing stop-gained PTEN mutations. Through counteraction of CD8+ T cell-mediated cytotoxicity, PTENα leads to T cell dysfunction and accelerates immune-resistant cancer progression. Clinical analysis further uncovers that PTENα-active mutations suppress host immune responses and result in poor prognosis in cancer as relative to PTENα-inactive mutations. Furthermore, germline deletion of Ptenα in mice increases cell susceptibility to immune attack through augmenting stress granule formation and limiting synthesis of peroxidases, leading to massive oxidative cell death and severe inflammatory damage. We propose that PTENα protects tumor from T cell killing and thus PTENα is a potential target in antitumor immunotherapy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Neoplasias/enzimologia , Neoplasias/imunologia , PTEN Fosfo-Hidrolase/imunologia , Animais , Linfócitos T CD8-Positivos/enzimologia , Feminino , Humanos , Imunossupressão , Isoenzimas/genética , Isoenzimas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Neoplasias/genética , PTEN Fosfo-Hidrolase/genética , Evasão Tumoral
3.
Infect Drug Resist ; 14: 2533-2542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234481

RESUMO

The pharmacokinetic/pharmacodynamic (PK/PD) parameter for evaluating the efficacy of vancomycin is now recommended to target an AUC/MIC (area under the curve, AUC; minimum inhibitory concentration, MIC) ratio of 400 to 600, and trough concentration should not be used as a substitute. We report a case of intracranial infection caused by methicillin-resistant Staphylococcus epidermidis (MRSE), which was sensitive to vancomycin (MIC=2µg/mL) and linezolid (MIC=4µg/mL). The trough concentration of vancomycin in serum was 18.3 µg/mL, and the vancomycin concentration in CSF was 5.0 µg/mL, all within normal range. However, the AUC/MIC ratio was calculated to be 125 mg·h·L-1, unable to reach target AUC/MIC. Vancomycin was replaced with linezolid after 36 days of treatment due to poor outcome, and the patient was eventually cured. Further, 23 cases of intracranial methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) infections were reported, of which 1 case with MRSA had a vancomycin MIC of 1 µg/mL, while the remaining 22 cases had vancomycin MICs >1 µg/mL. The linezolid-containing regimen was used after drug susceptibility results or if the initial treatment failed, leading to recovery in 19 patients, microbial clearance in 3 patients, and treatment failure in 1 case. In conclusion, vancomycin dosing should be based on AUC-guided dosing and monitoring. When the vancomycin MIC of MRSA/MRCoNS is >1 µg/mL, the target AUC/MIC may not be achieved. In such cases, linezolid can effectively be considered as a good alternative to vancomycin.

4.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206257

RESUMO

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that modulate innate immune responses and play essential roles in the pathogenesis of heart diseases. Although important, the molecular mechanisms controlling cardiac TLR genes expression have not been clearly addressed. This study examined the expression pattern of Tlr1, Tlr2, Tlr3, Tlr4, Tlr5, Tlr6, Tlr7, Tlr8, and Tlr9 in normal and disease-stressed mouse hearts. Our results demonstrated that the expression levels of cardiac Tlr3, Tlr7, Tlr8, and Tlr9 increased with age between neonatal and adult developmental stages, whereas the expression of Tlr5 decreased with age. Furthermore, pathological stress increased the expression levels of Tlr2, Tlr4, Tlr5, Tlr7, Tlr8, and Tlr9. Hippo-YAP signaling is essential for heart development and homeostasis maintenance, and YAP/TEAD1 complex is the terminal effector of this pathway. Here we found that TEAD1 directly bound genomic regions adjacent to Tlr1, Tlr2, Tlr3, Tlr4, Tlr5, Tlr6, Tlr7, and Tlr9. In vitro, luciferase reporter data suggest that YAP/TEAD1 repression of Tlr4 depends on a conserved TEAD1 binding motif near Tlr4 transcription start site. In vivo, cardiomyocyte-specific YAP depletion increased the expression of most examined TLR genes, activated the synthesis of pro-inflammatory cytokines, and predisposed the heart to lipopolysaccharide stress. In conclusion, our data indicate that the expression of cardiac TLR genes is associated with age and activated by pathological stress and suggest that YAP/TEAD1 complex is a default repressor of cardiac TLR genes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ligação a DNA/metabolismo , Imunidade Inata , Miócitos Cardíacos/metabolismo , Receptores Toll-Like/genética , Fatores de Transcrição/metabolismo , Fatores Etários , Animais , Citocinas/metabolismo , Regulação da Expressão Gênica , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
5.
Waste Manag ; 132: 142-150, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34332370

RESUMO

More food waste (FW) is desired to be treated in a certain processing period, while the degradation pattern of biochemical fractions during FW bioevaporation was significantly influenced by the organic loading (OL). Lower OL facilitated the lipids degradation, while higher OL favored the protein degradation. It was the more porous structure and abundant oxygen accelerated the lipids degradation, and the rapid proliferation of aerobic microorganisms compensated for the low protein degradation in lower OL. Detailly, 76.8% of the lipids was degraded in the trial with OL of 1.04 kg VSFW/kg TSBS (Trial A), but in the trial with OL of 3.16 kg VSFW/kg TSBS (Trial C) it was only 0.5%. For protein, the degradation was different that 17.5% of the protein was degraded in Trial A, whereas 69.1% was degraded in Trial C. Lipids degradation contributed 63.0% to the metabolic heat in Trial A, but its contribution in Trial C was only 0.5%. For protein, it contributed 4.1% to the metabolic heat in Trial A, but in Trial C it accounted for 53.6%. In addition, the degradation of carbohydrates (71.6-80.8%) and their contribution to metabolic heat (32.8-45.9%) were comparable in all trials, thus OL had little effect on carbohydrates degradation. Results from this study could provide important guideline for FW practical disposal during their biological treatment.


Assuntos
Eliminação de Resíduos , Reatores Biológicos , Carboidratos , Alimentos
6.
Eur J Neurol ; 28(11): 3774-3783, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34255403

RESUMO

BACKGROUND AND PURPOSE: The purpose was to provide an overview of genotype and phenotype distribution in a cohort of patients with Charcot-Marie-Tooth disease (CMT) and related disorders from central south China. METHODS: In all, 435 patients were enrolled and detailed clinical data were collected. Multiplex ligation-dependent probe amplification for PMP22 duplication/deletion and CMT multi-gene panel sequencing were performed. Whole exome sequencing was further applied in the remaining patients who failed to achieve molecular diagnosis. RESULTS: Among the 435 patients, 216 had CMT1, 14 had hereditary neuropathy with pressure palsies (HNPP), 178 had CMT2, 24 had distal hereditary motor neuropathy (dHMN) and three had hereditary sensory and autonomic neuropathy (HSAN). The overall molecular diagnosis rate was 70%: 75.7% in CMT1, 100% in HNPP, 64.6% in CMT2, 41.7% in dHMN and 33.3% in HSAN. The most common four genotypes accounted for 68.9% of molecular diagnosed patients. Relatively frequent causes were missense changes in PMP22 (4.6%) and SH3TC2 (2.3%) in CMT1; and GDAP1 (5.1%), IGHMBP2 (4.5%) and MORC2 (3.9%) in CMT2. Twenty of 160 detected pathogenic variants and the associated phenotypes have not been previously reported. Broad phenotype spectra were observed in six genes, amongst which the pathogenic variants in BAG3 and SPTLC1 were detected in two sporadic patients presenting with the CMT2 phenotype. CONCLUSIONS: Our results provided a unique genotypic and phenotypic landscape of patients with CMT and related disorders from central south China, including a relatively high proportion of CMT2 and lower occurrence of PMP22 duplication. The broad phenotype spectra in certain genes have advanced our understanding of CMT.


Assuntos
Doença de Charcot-Marie-Tooth , Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/genética , China/epidemiologia , Proteínas de Ligação a DNA , Genótipo , Humanos , Fenótipo , Fatores de Transcrição
7.
Am J Transl Res ; 13(4): 2702-2709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017431

RESUMO

OBJECTIVE: To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats. METHODS: Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E2 (PGE2), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured. RESULTS: Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE2 (all P<0.05). CONCLUSION: Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.

8.
J Vis Exp ; (169)2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33779621

RESUMO

Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis in mammals, and brown adipocytes (BAs) are the functional units of BAT. BAs contain both multilocular lipid droplets and abundant mitochondria, and they express uncoupling protein 1 (UCP1). BAs are categorized into two sub-types based on their origin: embryo derived classical BAs (cBAs) and white adipocytes derived BAs. Due to their relatively low density, BAs cannot be isolated from BAT with traditional centrifugation method. In this study, a new method was developed to isolate BAs from mice for gene and protein expression analysis. In this protocol, interscapular BAT from adult mice was digested with Collagenase and Dispase solution, and the dissociated BAs were enriched with 6% iodixanol solution. Isolated BAs were then lysed with Trizol reagent for simultaneous isolation of RNA, DNA, and protein. After RNA isolation, the organic phase of the lysate was used for protein extraction. Our data showed that 6% iodixanol solution efficiently enriched BAs without interfering with follow-up gene and protein expression studies. Platelet-derived growth factor (PDGF) is a growth factor that regulates the growth and proliferation of mesenchymal cells. Compared to the brown adipose tissue, isolated BAs had significantly higher expression of Pdgfa. In summary, this new method provides a platform for studying the biology of brown adipocytes at a single cell-type level.


Assuntos
Adipócitos Marrons/citologia , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/citologia , Regulação da Expressão Gênica , Proteínas/genética , Proteínas/metabolismo , Escápula/citologia , Tecido Adiposo Marrom/metabolismo , Animais , Separação Celular/métodos , Camundongos , Escápula/metabolismo
9.
Bioorg Chem ; 108: 104653, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33517002

RESUMO

Pyruvate kinase M2 isoform (PKM2) plays a key role in cancer progression through both metabolic and non-metabolic functions, thus it is recognized as a potential target for cancer diagnosis and treatment. In this study, we discovered a sulfonamide-dithiocarbamate compound 8a as a novel PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8a analogs were designed and synthesized for screening as potent PKM2 activators. Among them, compound 8b (AC50 = 0.136 µM) and 8k (AC50 = 0.056 µM) showed higher PKM2 activation activities than positive control NZT (AC50 = 0.228 µM), and they (IC50 < 1 µM) exhibited more significant anti-proliferative activities against human tumor cell lines than NZT (IC50 > 10 µM). Especially, compound 8k inhibited the proliferation of multiple cancer cells, but showed little toxicity on normal cells. In addition, we found that compound 8k inhibit the colony formation of MCF7 cells. Western blot analysis demonstrated that 8k could reduce PKM2 nuclear localization and block the downstream signaling pathway of PKM2, resulting in suppression of tumor cell proliferation. Overall, compound 8k may be a promising candidate for further mechanistic investigation of PKM2 and cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Membrana/antagonistas & inibidores , Piperazina/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proteínas de Transporte/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Proteínas de Membrana/metabolismo , Estrutura Molecular , Piperazina/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Hormônios Tireóideos/metabolismo
10.
EMBO Rep ; 22(2): e51162, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33393230

RESUMO

Although iron is required for cell proliferation, iron-dependent programmed cell death serves as a critical barrier to tumor growth and metastasis. Emerging evidence suggests that iron-mediated lipid oxidation also facilitates immune eradication of cancer. However, the regulatory mechanisms of iron metabolism in cancer remain unclear. Here we identify OTUD1 as the deubiquitinase of iron-responsive element-binding protein 2 (IREB2), selectively reduced in colorectal cancer. Clinically, downregulation of OTUD1 is highly correlated with poor outcome of cancer. Mechanistically, OTUD1 promotes transferrin receptor protein 1 (TFRC)-mediated iron transportation through deubiquitinating and stabilizing IREB2, leading to increased ROS generation and ferroptosis. Moreover, the presence of OTUD1 promotes the release of damage-associated molecular patterns (DAMPs), which in turn recruits the leukocytes and strengthens host immune response. Reciprocally, depletion of OTUD1 limits tumor-reactive T-cell accumulation and exacerbates colon cancer progression. Our data demonstrate that OTUD1 plays a stimulatory role in iron transportation and highlight the importance of OTUD1-IREB2-TFRC signaling axis in host antitumor immunity.


Assuntos
Ferroptose , Ferro/metabolismo , Neoplasias/imunologia , Proteases Específicas de Ubiquitina , Antígenos CD , Humanos , Proteína 2 Reguladora do Ferro , Receptores da Transferrina , Transdução de Sinais , Linfócitos T , Proteases Específicas de Ubiquitina/metabolismo
11.
Entropy (Basel) ; 22(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33287002

RESUMO

Functional brain network (FBN) is an intuitive expression of the dynamic neural activity interaction between different neurons, neuron clusters, or cerebral cortex regions. It can characterize the brain network topology and dynamic properties. The method of building an FBN to characterize the features of the brain network accurately and effectively is a challenging subject. Entropy can effectively describe the complexity, non-linearity, and uncertainty of electroencephalogram (EEG) signals. As a relatively new research direction, the research of the FBN construction method based on EEG data of fatigue driving has broad prospects. Therefore, it is of great significance to study the entropy-based FBN construction. We focus on selecting appropriate entropy features to characterize EEG signals and construct an FBN. On the real data set of fatigue driving, FBN models based on different entropies are constructed to identify the state of fatigue driving. Through analyzing network measurement indicators, the experiment shows that the FBN model based on fuzzy entropy can achieve excellent classification recognition rate and good classification stability. In addition, when compared with the other model based on the same data set, our model could obtain a higher accuracy and more stable classification results even if the length of the intercepted EEG signal is different.

12.
Front Neurol ; 11: 603003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381078

RESUMO

Background and Objectives: Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies. The objectives of this study were to report the clinical and genetic features of dHMN patients in a Chinese cohort. Aims and Methods: We performed clinical assessments and whole-exome sequencing in 24 dHMN families from Mainland China. We conducted a retrospective analysis of the data and investigated the frequency and clinical features of patients with a confirmed mutation. Results: Two novel heterozygous mutations in GARS, c.373G>C (p.E125Q) and c.1015G>A (p.G339R), were identified and corresponded to the typical dHMN-V phenotype. Together with families with WARS, SORD, SIGMAR1, and HSPB1 mutations, 29.2% of families (7/24) acquired a definite genetic diagnosis. One novel heterozygous variant of uncertain significance, c.1834G>A (p.G612S) in LRSAM1, was identified in a patient with mild dHMN phenotype. Conclusion: Our study expanded the mutation spectrum of GARS mutations and added evidence that GARS mutations are associated with both axonal Charcot-Marie-Tooth and dHMN phenotypes. Mutations in genes encoding aminoamide tRNA synthetase (ARS) might be a frequent cause of autosomal dominant-dHMN, and SORD mutation might account for a majority of autosomal recessive-dHMN cases. The relatively low genetic diagnosis yield indicated more causative dHMN genes need to be discovered.

13.
Sci Rep ; 10(1): 20335, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230135

RESUMO

Brown adipose tissue (BAT) is the primary non-shivering thermogenesis organ in mammals, which plays essential roles in maintaining the body temperature of infants. Although the development of BAT during embryogenesis has been well addressed in rodents, how BAT grows after birth remains unknown. Using mouse interscapular BAT (iBAT) as an example, we studied the cellular and molecular mechanisms that regulate postnatal BAT growth. By analyzing the developmental dynamics of brown adipocytes (BAs), we found that BAs size enlargement partially accounts for iBAT growth. By investigating the BAs cell cycle activities, we confirmed the presence of proliferative BAs in the neonatal mice. Two weeks after birth, most of the BAs exit cell cycle, and the further expansion of the BAT was mainly due to lipogenesis-mediated BAs volume increase. Microscopy and fluorescence-activated cell sorting analyses suggest that most BAs are mononuclear and diploid. Based on the developmental dynamics of brown adipocytes, we propose that the murine iBAT has two different growth phases between birth and weaning: increase of BAs size and number in the first two weeks, and BAs size enlargement thereafter. In summary, our data demonstrate that both lipogenesis and proliferation of BAs contribute to postnatal iBAT growth in mice.


Assuntos
Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/crescimento & desenvolvimento , Crescimento Celular , Proliferação de Células/fisiologia , Lipogênese/fisiologia , Animais , Animais Recém-Nascidos , Tamanho Celular , Células Cultivadas , Metabolismo Energético/fisiologia , Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Obesidade Pediátrica/metabolismo , Termogênese/fisiologia , Triglicerídeos/metabolismo
14.
J Nanobiotechnology ; 18(1): 146, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076924

RESUMO

BACKGROUNDS: Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors. METHODS: In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer. RESULTS: The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone-vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs. CONCLUSIONS: Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Tratamento Farmacológico , Feminino , Humanos , Verde de Indocianina/análogos & derivados , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/administração & dosagem , Povidona/análogos & derivados
15.
ACS Nano ; 14(10): 14134-14145, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33044056

RESUMO

Flexible and lightweight high-performance electromagnetic interference shielding materials with minimal thickness, excellent mechanical properties, and outstanding reliability are highly desired in the field of fifth-generation (5G) communication, yet remain extremely challenging to manufacture. Herein, we prepared an ultrathin densified carbon nanotube (CNT) film with superior mechanical properties and ultrahigh shielding effectiveness. Upon complete removal of impurities in pristine CNT film, charge separation in individual CNTs induced by polar molecules leads to strong CNT-CNT attraction and film densification, which significantly improve the electrical conductivity, shielding performance, and mechanical strength. The tensile strength is up to 822 ± 21 MPa, meanwhile the electrical conductivity is as high as 902,712 S/m, and the density is only 1.39 g cm-3. Notably, the shielding effectiveness is over 51 dB with a thickness of merely 1.85 µm in the broad frequency range of 4-18 GHz, and it reaches to ∼82 dB at 6.36 µm and ∼101 dB at 14.7 µm, respectively. Further, such CNT film exhibits excellent reliability after an extended period in strong acid/alkali, high temperature, and high humidity. It demonstrates the best overall performance among representative shielding materials by far, representing a critical breakthrough in the preparation of shielding film toward applications in wearable electronics and 5G communication.

16.
Nat Commun ; 11(1): 4666, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938943

RESUMO

Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show that loss of Xinß, a newly-identified component of ICDs, results in cardiomyocyte proliferation defects and cardiomyopathy. We uncovered a role for Xinß in signaling via the Hippo-YAP pathway by recruiting NF2 to the ICD to modulate cardiac function. In Xinß mutant hearts levels of phosphorylated NF2 are substantially reduced, suggesting an impairment of Hippo-YAP signaling. Cardiac-specific overexpression of YAP rescues cardiac defects in Xinß knock-out mice-indicating a functional and genetic interaction between Xinß and YAP. Our study reveals a molecular mechanism by which cardiac-expressed intercalated disc protein Xinß modulates Hippo-YAP signaling to control heart development and cardiac function in a tissue specific manner. Consequently, this pathway may represent a therapeutic target for the treatment of cardiovascular diseases.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas com Domínio LIM/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Cardiomiopatia Dilatada/genética , Comunicação Celular , Proteínas de Ciclo Celular/genética , Proliferação de Células , Proteínas do Citoesqueleto/genética , Proteínas de Ligação a DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Ventrículos do Coração/crescimento & desenvolvimento , Proteínas com Domínio LIM/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Miócitos Cardíacos/citologia , Miócitos Cardíacos/patologia , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Proteínas Nucleares/genética , Transdução de Sinais
17.
Pharmacol Res ; 161: 105099, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32739427

RESUMO

As a type of fear relapse, fear renewal compromises the efficacy of fear extinction, which serves as the laboratory analog of exposure therapy (a therapeutic strategy for anxiety disorders). Interventions aiming to prevent fear renewal would thus benefit exposure therapy. To date, it remains unknown whether central adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation could produce inhibitory effects on fear renewal. Here, using pharmacological approach and virus-mediated gene overexpression technique, we demonstrated that activation of AMPK in dorsal hippocampus shortly before fear extinction training completely abolished subsequent fear renewal in male mice without affecting other types of fear relapse, including spontaneous recovery of fear and fear reinstatement. Furthermore, we also found that metformin, a first-line antidiabetic drug, was capable of preventing fear renewal in male mice by stimulating AMPK in dorsal hippocampus. Collectively, our study provides insight into the role of hippocampal AMPK in regulation of fear renewal and indicates that increasing activity of hippocampal AMPK can prevent fear renewal, thus enhancing the potency of exposure therapy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Comportamento Animal/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Extinção Psicológica , Medo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Terapia Implosiva , Metformina/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Animais , Ativação Enzimática , Hipocampo/enzimologia , Masculino , Camundongos Endogâmicos C57BL
18.
ACS Appl Mater Interfaces ; 12(37): 42420-42429, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32833419

RESUMO

Highly sensitive and stretchable strain sensors have attracted considerable attention due to their promising applications in human motion detection, soft robot, wearable electronics, etc. However, there is still a trade-off between high sensitivity and high stretchability. Here, we reported a stretchable strain sensor by sandwiching reduced graphene oxide (RGO)-coated polystyrene microspheres (PS@RGO) and silver nanowires (AgNWs) conductive hybrids in an elastic polydimethylsiloxane (PDMS) matrix. Due to the synergistic effect of PS@RGO and AgNWs, the PDMS/PS@RGO/AgNWs/PDMS sensor exhibits a high initial electrical conductivity of 8791 S m-1, wide working range of 0-230%, large gauge factor of 11 at 0-60% of strain and 47 at 100%-230% of strain with a high linear coefficient of 0.9594 and 0.9947, respectively, low limit of detection (LOD) of 1% of strain, and excellent long-term stability over 1000 stretching/releasing cycles under 50% strain. Furthermore, the strain sensor has been demonstrated in detecting human body motion and fan rotation with high stretchability and stability, showing potential application in intelligent robot and Internet of things.

20.
Infect Dis Poverty ; 9(1): 47, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381058

RESUMO

BACKGROUND: The incidence of brucellosis, which is caused by the Brucella species of bacteria, is rapidly rising worldwide; however, few studies have investigated the immune response to this pathogen and clinical biochemical features. In this paper, we examined the levels of various cytokines and inflammatory factors as well as clinical course characteristics in patients with brucellosis, in order to provide evidence for the diagnosis, assessment, and prognosis of this infectious disease. METHODS: A total of 191 brucellosis inpatients (50 acute cases and 141 chronic cases), as well as 60 healthy control subjects, were included in the analysis. We investigated changes in the levels of six cytokines (IL-4, IL-6, IL-10, IL-17, TNF-α, INF-γ) and related clinical biochemical markers in patients with acute and chronic brucellosis in Xinjiang, China. Possible factors were statistically analyzed using the t test, χ2 test, z test and a multivariate logistic stepwise regression test. RESULTS: We found that IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels were higher in those with brucellosis than in controls (P <  0.05). With regard to disease progression, procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly higher in those with an acute infection compared to chronic cases (P <  0.05). We found that the expression of all six cytokines tested was closely related to the degree of brucellosis using univariate logistic regression; however, only IL-6 and INF-γ levels were independent factors associated with the severity of brucellosis. CONCLUSIONS: Assessing cytokine levels in patients with acute and chronic brucellosis is not only useful for detecting the immune response, but can also be indicative of the severity of brucellosis. In particular, we propose IL-6 and INF-γ levels may be useful independent predictive factors in the clinical evaluation and diagnosis of brucellosis.


Assuntos
Brucelose/diagnóstico , Interferons/sangue , Interleucinas/sangue , Adolescente , Adulto , Idoso , Brucelose/sangue , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...