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The interfacial effect is widely used to optimize the properties of ferroelectric nanocomposites, however, there is still a lack of direct evidence to understand its underlying mechanisms limited by the nano size and complex structures. Here, taking piezoelectricity, for example, the mechanism of interfacial polarization in barium titanate/poly(vinylidene fluoride-ran-trifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite is revealed at multiple scales by combining Kelvin probe force microscope (KPFM) with theoretical stimulation. The results prove that the mismatch of permittivity between matrix and filler leads to the accumulation of charges, which in turn induces local polarization in the interfacial region, and thus can promote piezoelectricity independently. Furthermore, the strategy of interfacial polarization to enhance piezoelectricity is extended and validated in other two similar nanocomposites. This work uncovers the mechanism of interfacial polarization and paves newfangled insights to boost performances in ferroelectric nanocomposites.
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MXenes have shown great potential as an emerging two-dimensional (2D) material for micro-supercapacitors (MSCs) due to their high conductivity, rich surface chemistry, and high capacity. However, MXene sheets inherently tend to lay flat on the substrate during film formation to assemble into compact stacked structures, which hinders ion accessibility and prolongs ion transport paths, leading to highly dependent electrochemical properties on the thickness of the film. Here, we demonstrate a vertically aligned Ti3C2Tx MXene based micro-supercapacitor with an excellent electrochemical performance by a liquid nitrogen-assisted freeze-drying method. The vertical arrangement of the 2D MXene sheets allows for directional ion transport, enabling the vertical-MXene based MSCs to exhibit thickness-independent electrochemical properties even in thick films. In addition, the MSCs displayed a high areal capacitance of 87 mF cm-2 at 10 mV s-1 along with an excellent stability of â¼87.4% after 10 000 charge-discharge cycles. Furthermore, the vertical-MXene approach proposed here is scalable and can be extended to other systems involving directional transport.
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Diabetes mellitus has been a major public health problem worldwide, characterized by insulin resistance and dysfunction of ß-cells. A previous study showed that Kindlin-2 loss in ß-cells dramatically reduces insulin secretion and decreases ß-cell mass, resulting in severe diabetes-like phenotypes. It suggests that Kindlin-2 in ß-cells play an important role in regulating glucose homeostasis. However, the effect of Kindlin-2 on the function of ß-cells under chronic hyperglycemia in diabetes has not been explored. Here we report that Kindlin-2 overexpression ameliorates diabetes and improves insulin secretion in mice induced by streptozocin. In contrast, Kindlin-2 insufficiency exacerbates diabetes and promotes ß-cells dysfunction and inflammation in ß-cells induced by a high-fat diet (HFD). In vitro, Kindlin-2 overexpression prevented high-glucose (HG)-induced dysfunction in ß-cells. Kindlin-2 overexpression also decreased the expression of pro-inflammatory cytokines and NLRP3 inflammasome expression in ß-cells exposed to HG. Furthermore, the loss of Kindlin-2 aggravates the expression of inflammatory cytokines and NLRP3 induced by HG in ß-cells. Collectively, we demonstrate that Kindlin-2 protects against diabetes by inhibiting NLRP3 inflammasome activation.
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Proteínas do Citoesqueleto , Diabetes Mellitus Experimental , Inflamassomos , Células Secretoras de Insulina , Animais , Citocinas/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Inflamassomos/metabolismo , Células Secretoras de Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Musculares/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
BACKGROUND: Retinoblastoma protein (Rb) supports vasoprotective E2F Transcription Factor 1 (E2f1)/Dihydrofolate Reductase (Dhfr) pathway activity in endothelial cells. Cyclin I (Ccni) promotes Cyclin-Dependent Kinase-5 (Cdk5)-mediated Rb phosphorylation. Therefore, we hypothesized that endothelial Ccni may regulate cardiovascular homeostasis, vessel remodeling, and abdominal aortic aneurysm (AAA) formation. METHODS: Aortic CCNI mRNA expression was analyzed in the Gene Expression Omnibus (GEO) GSE57691 cohort consisting of AAA patients (n = 39) and healthy controls (n = 10). We employed wild-type (WT) mice and endothelial Ccni knockout (Ccnifl/flTie2-Cre) mice to conduct in vivo and ex vivo experimentation using an Angiotensin (Ang) II hypertension model and a CaCl2 AAA model. Mice were assessed for Rb/E2f1/Dhfr signaling, biopterin (i.e., biopterin [B], dihydrobiopterin [BH2], and tetrahydrobiopterin [BH4]) production, cardiovascular homeostasis, vessel remodeling, and AAA formation. RESULTS: Aortic CCNI mRNA expression was downregulated in AAA patients. Both Ang II- and CaCl2-induced WT mice showed aortic Ccni upregulation coupled with vasculoprotective upregulation of Rb/E2f1/Dhfr signaling and biopterins. Endothelial Ccni knockout downregulated medial Rb/E2f1/Dhfr signaling and biopterins in Ang II-induced hypertensive mice, which exacerbated eNos uncoupling and H2O2 production. Endothelial Ccni knockout impaired in vivo hemodynamic responses and endothelium-dependent vasodilatation in ex vivo mesenteric arteries in response to Ang II. Endothelial Ccni knockout exacerbated mesenteric artery remodeling and AAA risk in response to Ang II and CaCl2. CONCLUSIONS: Endothelial Ccni acts as a critical negative regulator of eNos uncoupling-mediated ROS generation and thereby reduces vulnerability to hypertension-induced vascular remodeling and AAA development in mice.
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Angiotensina II , Aneurisma da Aorta Abdominal , Hipertensão , Remodelação Vascular , Angiotensina II/farmacologia , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/prevenção & controle , Biopterinas/metabolismo , Cloreto de Cálcio/metabolismo , Ciclina I/metabolismo , Proteína Rica em Cisteína 61/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Endotélio/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Hipertensão/genética , Hipertensão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/metabolismo , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismoRESUMO
Background: Dual antiplatelet therapy (DAPT) with potent P2Y12 inhibitor is the cornerstone of acute coronary syndrome (ACS) management. Balancing the effects of different strategies of antiplatelet therapy including DAPT de-escalation, potent P2Y12 inhibitor monotherapy, and conventional DAPT is a hot topic. Methods: A systematic search was conducted from the MEDLINE, PubMed, and Embase through October 2021 to identify various DAPT strategies in randomized controlled trials (RCTs) for treatment of ACS patients after undergoing PCI with drug-eluting stent (DES). The network meta-analysis was performed to investigate the net clinic benefit of the DAPT de-escalation, potent P2Y12 inhibitor monotherapy, as well as conventional DAPT. The primary outcome was net adverse clinical events, defined as a composite of major bleeding and cardiac death, myocardial infarction, stroke, stent thrombosis, or target-vessel revascularization. The secondary outcomes include major adverse cardiac events and trial-defined major or minor bleeding. Results: A total of 14 RCTs with 63,982 patients were included. The DAPT de-escalation was associated with a lower risk of the primary outcome compared with potent P2Y12 inhibitor monotherapy (De-escalation vs monotherapy odds ratio (OR): 0.72 95% confidence interval (CI): 0.55-0.96), and other antiplatelet strategies (De-escalation vs clopidogrel + aspirin OR: 0.49 95% CI: 0.39-0.63; De-escalation vs prasugrel + aspirin OR: 0.76 95% CI: 0.59-0.98; De-escalation vs ticagrelor + aspirin OR: 0.76 95% CI: 0.55-0.90). There were no statistical differences in the incidence of bleeding (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.73 95% CI: 0.47-1.12) and major adverse cardiac events (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.79 95% CI: 0.59-1.08) between DAPT de-escalation and potent P2Y12 inhibitor monotherapy. Conclusions: This network meta-analysis showed that DAPT de-escalation would reduce the net adverse clinical events, compared with potent P2Y12 inhibitor monotherapy, for ACS patients undergone PCI treatment.
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BACKGROUND: Patients hospitalized with chronic obstructive pulmonary disease (COPD) exacerbations are unable to complete the pulmonary function test reliably due to their poor health conditions. Creating an easy-to-use instrument to identify the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage will offer valuable information that assists clinicians to choose appropriate clinical care to decrease the mortality in these patients. The objective of this study was to develop a prediction model to identify the GOLD stage in the hospitalized exacerbation of chronic obstructive pulmonary disease (ECOPD) patients. METHODS: This prospective study involved 155 patients hospitalized for ECOPD. All participants completed lung function tests and the collection of blood neutrophils and demographic parameters. Receiver operating characteristic (ROC) curve was plotted based on the data of 155 patients, and was used to analyze the disease severity predictive capability of blood neutrophils and demographic parameters. A support vector regression (SVR) based GOLD stage prediction model was built using the training data set (75%), whose accuracy was then verified by the testing data set (25%). RESULTS: The percentage of blood neutrophils (denoted as NEU%) combined with the demographic parameters was associated with a higher risk to severe episode of ECOPD. The area under the ROC curve was 0.84. The SVR model managed to predict the GOLD stage with an accuracy of 90.24%. The root-mean-square error (RMSE) of the forced expiratory volume in one second as the percentage of the predicted value (denoted as FEV1%pred) was 8.84%. CONCLUSIONS: The NEU% and demographic parameters are associated with the pulmonary function of the hospitalized ECOPD patients. The established prediction model could assist clinicians in diagnosing GOLD stage and planning appropriate clinical care.
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Demografia , Neutrófilos , Doença Pulmonar Obstrutiva Crônica , Medição de Risco/métodos , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/sangue , Curva ROC , Testes de Função Respiratória , Fatores de RiscoRESUMO
Two new ß-dihydroagarofuran-type sesquiterpenes 1ß,2α,6α,8ß,15- pentaacetoxy- 9α-benzoyloxy- ß-dihydroagarofuran (1) and 1ß,2ß,6α,15-tetraacetoxy-9ß-benzoyloxy- ß-dihydroagarofuran (2), together with five known abietane diterpenoids (3-7) were isolated from ethyl acetate extract of stems of Tripterygium wilfordii. Their structures were elucidated on the basis of detailed spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against A549, HOS and MCF-7. Among them, compounds 4 and 5 exhibited manifest inhibition on A549, HOS and MCF-7 cancer cell lines.
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Medicamentos de Ervas Chinesas , Sesquiterpenos , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Sesquiterpenos/farmacologia , TripterygiumRESUMO
The potential screening effect of one-dimensional ZnO nanorods from carriers has been theoretically proved to severely limit its piezoelectricity, but its exact mechanism needs to be further revealed in experiments to guide the design of piezoelectric semiconductors. Here, a discretely structured design was proposed to prevent the free carriers from tunneling among adjacent ZnO nanorods for suppressing the screening effect. Piezoresponse force microscope and finite element analysis were employed in combination to uncover the underlying mechanism in experiment. Further, the output voltage of this discretely structured device was 1.62 times higher than that of the nondesigned device, which clearly authenticates this suppression behavior. Besides, this design prompts an unexpected improvement in flexibility, where the flexural modulus of this piezo-film was reduced by 35.74%. Notably, this work opens a new way to understand the potential screening effect, as expected, and to advance the development of piezo-electronics toward better piezoelectricity and more excellent flexibility.
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Cardiovascular disease (CVD) is a major cause of global mortality. The proper functioning of the endothelial layer of arteries is crucial to cardiovascular health. Retinoblastoma protein (Rb), encoded by the Rb1 gene, has been shown to offer vasoprotective effects. Herein, we investigated endothelial Rb's effects on arterial function using an endothelial-specific conditional Rb1 knockout (Rb cKO) mouse model. We found that Rb deficiency reduced dihydrofolate reductase (DHFR) activity and downstream NO production in mouse aortic endothelial cells and blocked arterial vasodilation in an endothelial DHFR-dependent manner. Rb deficiency also increased phenylephrine-triggered arterial vasoconstriction, BP levels, and pathological aortic remodeling without significantly affecting prostanoid synthesis. Employing an angiotensin II (AngII)-stimulated apolipoprotein E knockout (apoE -/-) mice fed a standard, non-atherogenic diet, Rb deficiency increased aortic diameter, stimulated abdominal aortic aneurysm (AAA) development, and reduced survival. These pathological responses to Rb deficiency in AngII-stimulated apoE-/- mice were rescued by DHFR overexpression. Cumulatively, our findings reveal that endothelial Rb positively impacts arterial function by supporting vasoprotective endothelial DHFR/NO pathway activity, leading to reduced AAA development.
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Aneurisma da Aorta Abdominal/patologia , Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais , Tetra-Hidrofolato Desidrogenase/metabolismo , Animais , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Abdominal/fisiopatologia , Artérias/metabolismo , Pressão Sanguínea , Regulação para Baixo , Células Endoteliais/patologia , Camundongos , Óxido Nítrico Sintase Tipo III/metabolismo , Prostaglandinas/metabolismo , Proteína do Retinoblastoma/deficiência , Remodelação Vascular , Vasoconstrição , VasodilataçãoRESUMO
OBJECTIVE:: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. DESIGN:: Pilot randomized controlled trial. SETTING:: Three teaching hospitals in China. SUBJECTS:: Patients with knee osteoarthritis (Kellgren grade II or III). INTERVENTIONS:: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. MAIN MEASURES:: The primary outcome was response rate-the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. RESULTS:: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. CONCLUSION:: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.
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Terapia por Acupuntura , Osteoartrite do Joelho/terapia , Idoso , China , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Recuperação de Função Fisiológica , Método Simples-Cego , Resultado do TratamentoRESUMO
Acute lung injury (ALI) remains a high mortality rate with dramatic lung inflammation and alveolar epithelial cell death. Although fatty acid ß-oxidation (FAO) impairment has been implicated in the pathogenesis of ALI, whether Carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme for FAO, plays roles in lipopolysaccharide (LPS)-induced ALI remains unclear. Accordingly, we focused on exploring the effect of CPT1A in the context of ALI and the underlying mechanisms. We found that overexpression of CPT1A (AAV-CPT1A) effectively alleviated lung injury by reduction of lung wet-to-dry ratio, inflammatory cell infiltration, and protein levels in the BALF of ALI mice. Meanwhile, AAV-CPT1A significantly lessened histopathological changes and several cytokines' secretions. In contrast, blocking CPT1A with etomoxir augmented inflammatory responses and lung injury in ALI mice. Furthermore, we found that overexpression of CPT1A with lentivirus reduced the apoptosis rates of alveolar epithelial cells and the expression of apoptosis-related proteins induced by LPS in MLE12 cells, while etomoxir increased the apoptosis of MLE12 cells. Overexpression of CPT1A prevented the drop in bioenergetics, palmitate oxidation, and ATP levels. In conclusion, the results rendered CPT1A worthy of further development into a pharmaceutical drug for the treatment of ALI.
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Lesão Pulmonar Aguda , Compostos de Epóxi , Lipopolissacarídeos , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Lipopolissacarídeos/metabolismo , Pulmão/patologiaRESUMO
Continuous monitoring of blood pressure (BP) and multiparametric analysis of cardiac functions are crucial for the early diagnosis and therapy of cardiovascular diseases. However, existing monitoring approaches often suffer from bulky and intrusive apparatus, cumbersome testing procedures, and challenging data processing, hampering their applications in continuous monitoring. Here, a heterogeneously hierarchical piezoelectric composite is introduced for wearable continuous BP and cardiac function monitoring, overcoming the rigidity of ceramic and the insensitivity of polymer. By optimizing the hierarchical structure and components of the composite, the developed piezoelectric sensor delivers impressive performances, ensuring continuous and accurate monitoring of BP at Grade A level. Furthermore, the hemodynamic parameters are extracted from the detected signals, such as local pulse wave velocity, cardiac output, and stroke volume, all of which are in alignment with clinical results. Finally, the all-day tracking of cardiac function parameters validates the reliability and stability of the developed sensor, highlighting its potential for personalized healthcare systems, particularly in early diagnosis and timely intervention of cardiovascular disease.
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Dispositivos Eletrônicos Vestíveis , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Pressão Sanguínea , Análise de Onda de Pulso/instrumentação , Doenças Cardiovasculares/diagnóstico , HemodinâmicaRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.
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Piezoelectric semiconductor zinc oxide (ZnO) shows promising applications in many fields, however, its excellent piezoelectric performance is limited by the intrinsic screening effect. Forming p-n junction through interface engineering is an effective strategy to enhance its piezoelectric output, but the unclear regulation mechanism is a bottleneck in developing high-performance devices. In this work, the enhancement mechanism of interface engineering on the piezoelectric performance of ZnO nanorods (NRs) based devices is revealed from the perspective of carrier concentration. Both the theoretical and experimental results show that the piezoelectric output is significantly correlated with the carrier concentration, which is mainly attributed to the suppression of screening effect and the modulation of the device capacitance. After a reasonable matching design of carrier concentration, the piezoelectric potential of the ZnO NRs-based device is greatly enhanced by about 12 times. Apparently, these findings provide a fresh insight to further understand the enhancement mechanism of interface engineering on the electrical output of piezoelectric semiconductor devices, and provide effective support for the design of p-n junction piezoelectric devices.
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As an important part of human-machine interfaces, piezoelectric voice recognition has received extensive attention due to its unique self-powered nature. However, conventional voice recognition devices exhibit a limited response frequency band due to the intrinsic hardness and brittleness of piezoelectric ceramics or the flexibility of piezoelectric fibers. Here, we propose a cochlear-inspired multichannel piezoelectric acoustic sensor (MAS) based on gradient PVDF piezoelectric nanofibers for broadband voice recognition by a programmable electrospinning technique. Compared with the common electrospun PVDF membrane-based acoustic sensor, the developed MAS demonstrates the greatly 300%-broadened frequency band and the substantially 334.6%-enhanced piezoelectric output. More importantly, this MAS can serve as a high-fidelity auditory platform for music recording and human voice recognition, in which the classification accuracy rate can reach up to 100% in coordination with deep learning. The programmable bionic gradient piezoelectric nanofiber may provide a universal strategy for the development of intelligent bioelectronics.
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PURPOSES: To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men. METHODS: This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia. RESULTS: Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P < 0.01). Also 144 of 1,333(10.80%) patients presented Y chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls. CONCLUSIONS: There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.
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Aberrações Cromossômicas , Cromossomos Humanos Y , Infertilidade Masculina/genética , Povo Asiático/genética , Azoospermia/genética , Estudos de Casos e Controles , Deleção Cromossômica , Testes Genéticos , Humanos , Cariótipo , Masculino , Reação em Cadeia da Polimerase Multiplex , Oligospermia/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Espermatogênese/genéticaRESUMO
RYR2 mutation is clinically frequent in non-small cell lung cancer (NSCLC) with its function being elusive. We downloaded lung squamous cell carcinoma and lung adenocarcinoma samples from the TCGA database, split the samples into RYR2 mutant group (n = 337) and RYR2 wild group (n = 634), and established Kaplan-Meier curves. The results showed that RYR2 mutant group lived longer than the wild group (p = 0.027). Weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) yielded prognosis-related genes. Five mRNAs and 10 lncRNAs were selected to build survival prognostic models with other clinical features. The AUCs of 2 models are 0.622 and 0.565 for predicting survival at 3 years. Among these genes, the AUCs of DKK1 and GS1-115G20.1 expression levels were 0.607 and 0.560, respectively, which predicted the 3-year survival rate of NSCLC sufferers. GSEA identified an association of high DKK1 expression with TP53, MTOR, and VEGF expression. Several target miRNAs interacting with GS1-115G20.1 were observed to show the relationship with the phenotype, treatment, and survival of NSCLC. NSCLC patients with RYR2 mutation may obtain better prognosis by down-regulating DKK1 and up-regulating GS1-115G20.1.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação , Prognóstico , Regulação para CimaRESUMO
Background: To determine the congenital heart defect (CHD) prevalence and identify the associated risk factors in children within the multi-ethnic Yunnan Region of China. Methods: This is a prospective matched case-control screening study. Screening for CHD in children residing within 28 county districts of Yunnan Province during the period of January 2001 to December 2016 was conducted. A total of 2,421 and CHD cohort and 24,210 control cohort were derived from a total population of 400,855 children (under 18 years of age). Results: A total of 2,421 children were diagnosed with CHD, yielding a CHD prevalence of 6.04 cases per 1,000 children. The prevalence of CHD by sex was 6.54 per 1,000 females versus 5.59 per 1,000 males. The ethnic groups displaying the highest CHD prevalence were the Lisu (15.51 per 1,000), Achang (13.18 per 1,000), Jingpo (12.32 per 1,000), Naxi (9.68 per 1,000), and Tibetan (8.57 per 1,000), respectively. The most common CHD was atrial septal defect, amounting to 1.94 instances per 1,000 children. We identified a number of child-associated parameters that significantly correlated with greater CHD risk, such as lower mass at birth, shorter duration of gestation, and younger age at the time of screening. We also identified a number of maternal and familial risk factors. Conclusions: This ultrasonic color Doppler imaging study revealed a relatively commonplace prevalence of CHD. Moreover, the prevalence of CHD in Yunnan Region significantly varied with sex and ethnic status. Certain child-associated, maternal, and familial risk factors may contribute to CHD risk.
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ZnO is a typical piezoelectric semiconductor, and enhancing the piezoelectric output of ZnO-based devices is essential for their efficient applications. Surface engineering is an effective strategy to improve the piezoelectric output of ZnO-based devices, but its unclear regulation mechanism leads to a lack of reasonable guidance for device design. In this work, the regulation effect of the barrier layer in ZnO-based piezoelectric devices is systematically investigated from the carrier perspective through surface engineering, resulting in a significant improvement (nearly 10-fold) in the output performance of piezoelectric devices. The regulation mechanism of the ZnO-Cu2O p-n heterojunction devices on piezoelectric output is revealed in terms of built-in electric field, depletion layer width, and junction capacitance. These findings facilitate further insight into the enhancement mechanism of the piezoelectric output of ZnO-based devices and provide reasonable ideas for efficient device design.
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In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature. The in vitro release profile showed that bFGF could be released from bFGF-NPs or bFGF-NPs/hydrogel at an extended period, but the release rate of bFGF-NPs/hydrogel was much lower. In vivo experiments suggested that immunogenicity of bFGF improved significantly after being incorporated into the NPs/hydrogel composite, and strong humoral immunity was maintained for longer than 12 weeks. Furthermore, an in vivo protective anti-tumor immunity assay indicated that immunization with bFGF-NPs/hydrogel could induce significant suppression of the growth and metastases of tumors. Thus, the NPs/hydrogel composite may have great potential application as a novel vaccine delivery system.