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1.
J Physiol ; 602(2): 317-332, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38152023

RESUMO

It has been documented that increased sympathetic activity contributes to the development of cardiovascular diseases, such as hypertension. We previously reported that ß-arrestin-1, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)-22-3p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR-22-3p in ß-arrestin-1-mediated central cardiovascular regulation in hypertension. It was observed that miR-22-3p was upregulated in the RVLM of SHRs compared with normotensive Wistar-Kyoto (WKY) rats, and it was subsequently confirmed to target the ß-arrestin-1 gene using a dual-luciferase reporter assay. miR-22-3p was downregulated in the RVLM using adeno-associated virus with 'tough decoys', which caused a significant increase of ß-arrestin-1 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR-22-3p using lentivirus in the RVLM of WKY rats significantly increased BP. In in vitro PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR-22-3p inhibitor, and this effect could be abolished by ß-arrestin-1 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR-22-3p expression, and enhanced ß-arrestin-1 expression in the RVLM of SHRs. Activation of BV2 cells in vitro evoked a significant increase of miR-22-3p expression, and this BV2 cell culture medium was also able to facilitate miR-22-3p expression in PC12 cells. Collectively, our findings support a critical role for microglia-derived miR-22-3p in inhibiting ß-arrestin-1 in the RVLM, which is involved in central cardiovascular regulation in hypertension. KEY POINTS: Impairment of ß-arrestin-1 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of ß-arrestin-1 dysfunction in hypertension. miR-22-3p is implicated in multiple biological processes, but the role of miR-22-3p in central regulation of cardiovascular activity in hypertension remains unknown. We predicted that miR-22-3p could directly bind to the ß-arrestin-1 gene (Arrb1), and this hypothesis was confirmed by using a dual-luciferase reporter assay. Inhibition of ß-arrestin-1 by miR-22-3p was further verified in both in vivo and in vitro experiments. Furthermore, our results suggested miR-22-3p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho-excitation and hypertension. Our present study provides evidence that microglia-derived miR-22-3p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting ß-arrestin-1 in the RVLM.


Assuntos
Hipertensão , MicroRNAs , Animais , Ratos , beta-Arrestina 1/genética , beta-Arrestina 1/metabolismo , Pressão Sanguínea/fisiologia , Luciferases/metabolismo , Bulbo/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
2.
Small ; 20(3): e2304575, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37675819

RESUMO

The exponential interest in covalent organic frameworks (COFs) arises from the direct correlation between their diverse and intriguing properties and the modular design principle. However, the insufficient interlamellar interaction among COF nanosheets greatly hinders the formation of defect-free membranes. Therefore, developing a methodology for the facile fabrication of these materials remains an enticing and highly desirable objective. Herein, ultrahigh proton conductivity and superior stability are achieved by taking advantage of COF composite membranes where 2D TB-COF nanosheets are linked by 1D lignocellulosic nanofibrils (LCNFs) through π-π and electrostatic interactions to form a robust and ordered structure. Notably, the high concentration of -SO3 H groups within the COF pores and the abundant proton transport paths at COFs-LCNFs interfaces impart composite membranes ultrahigh proton conductivity (0.348 S cm-1 at 80 °C and 100% RH). Moreover, the directional migration of protons along the stacked nanochannels of COFs is facilitated by oxygen atoms on the keto groups, as demonstrated by density functional theory (DFT) calculations. The simple design concept and reliable operation of the demonstrated mixed-dimensional composite membrane are expected to provide an ideal platform for next-generation conductive materials.

3.
Planta ; 259(6): 138, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687380

RESUMO

MAIN CONCLUSION: The identification of a functional cinnamoyl-CoA reductase enzyme from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis offers the potential for enhancing trans-cinnamaldehyde production through genetic engineering. A significant accumulation of trans-cinnamaldehyde has been found in the bark tissues of C. cassia, used in traditional Chinese medicine. trans-Cinnamaldehyde exhibits various pharmacological properties such as anti-inflammatory, analgesic, and protection of the stomach and the digestive tract. However, further elucidation and characterization of the biosynthetic pathway for trans-cinnamaldehyde is required. In this study, we conducted an integrated analysis of trans-cinnamaldehyde accumulation profiles and transcriptomic data from five different C. cassia tissues to identify the genes involved in its biosynthesis. The transcriptome data we obtained included nearly all genes associated with the trans-cinnamaldehyde pathway, with the majority demonstrating high abundance in branch barks and trunk barks. We successfully cloned four C. cassia cinnamoyl-CoA reductases (CcCCRs), a key gene in trans-cinnamaldehyde biosynthesis. We found that the recombinant CcCCR1 protein was the only one that more efficiently converted cinnamoyl-CoA into trans-cinnamaldehyde. CcCCR1 exhibited approximately 14.7-fold higher catalytic efficiency (kcat/Km) compared to the Arabidopsis thaliana cinnamoyl-CoA reductase 1 (AtCCR1); therefore, it can be utilized for engineering higher trans-cinnamaldehyde production as previously reported. Molecular docking studies and mutagenesis experiments also validated the superior catalytic activity of CcCCR1 compared to AtCCR1. These findings provide valuable insights for the functional characterization of enzyme-coding genes and hold potential for future engineering of trans-cinnamaldehyde biosynthetic pathways.


Assuntos
Acroleína , Acroleína/análogos & derivados , Aldeído Oxirredutases , Cinnamomum aromaticum , Acroleína/metabolismo , Cinnamomum aromaticum/genética , Cinnamomum aromaticum/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Simulação de Acoplamento Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Casca de Planta/genética , Casca de Planta/metabolismo , Regulação da Expressão Gênica de Plantas
4.
Langmuir ; 40(1): 109-117, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38154122

RESUMO

Thermodynamically, perfect DNA hybridization can be formed between probes and their corresponding targets due to the favorable energy. However, this is not the case dynamically. Here, we use molecular dynamics (MD) simulations based on the oxDNA model to investigate the process of DNA microarray hybridization. In general, correlated hybrid DNA structures are formed, including one probe associated with several targets as well as one target hybrid with multiple probes leading to the target-mediated hybridization. The formation of these two types of correlated structures largely depends on the surface coverage of the DNA microarray. Moreover, DNA sequence, DNA length, and spacer length have an impact on the structural formation. Our findings shed light on the dynamics of DNA hybridization, which is important for the application of DNA microarray.


Assuntos
DNA , DNA/genética , DNA/química , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Sequência de Bases , Sondas de DNA/química
5.
Eur Radiol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38710788

RESUMO

OBJECTIVE: To compare the outcomes of totally percutaneous in situ microneedle puncture for left subclavian artery (LSA) fenestration (ISMF) and chimney technique in type B aortic dissection (TBAD) during thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Data on patients who underwent either chimney-TEVAR (n = 89) or ISMF-TEVAR (n = 113) from October 2018 to April 2022 were analyzed retrospectively. The primary outcomes were mortality and major complications at 30 days and during follow-up. RESULTS: The technical success rate was 84.3% in the chimney group and 93.8% in the ISMF group (p = 0.027). The incidence of immediate endoleakage was significantly higher in the chimney than ISMF group (15.7% vs 6.2%, respectively; p = 0.027). The 1- and 3-year survival rates in the chimney and ISMF groups were 98.9% ± 1.1% vs 98.1% ± 0.9% and 86.5% ± 6.3% vs 92.6% ± 4.1%, respectively (log-rank p = 0.715). The 3-year rate of cumulative freedom from branch occlusion in the chimney and ISMF group was 95.4% ± 2.3% vs 100%, respectively (log-rank p = 0.023). CONCLUSION: Both ISMF-TEVAR and chimney-TEVAR achieved satisfactory short- and mid-term outcomes for the preservation of the LSA in patients with TBAD. ISMF-TEVAR appears to offer better clinical outcomes with higher patency and lower reintervention rates. However, ISMF-TEVAR had longer operation times with higher procedure expenses. CLINICAL RELEVANCE STATEMENT: When LSA revascularization is required during TEVAR, in situ, fenestration, and chimney techniques are all safe and effective methods; in situ, fenestration-TEVAR appears to offer better clinical outcomes, but takes longer and is more complicated. KEY POINTS: LSA revascularization during TEVAR reduces post-operative complication rates. Both in situ ISMF-TEVAR and chimney-TEVAR are safe and effective techniques for the preservation of the LSA during TEVAR. The chimney technique is associated with a higher incidence of endoleakage and branch occlusion, but ISMF-TEVAR is a more complicated and expensive technique.

6.
Stat Med ; 43(4): 674-688, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38043523

RESUMO

Measures of substance concentration in urine, serum or other biological matrices often have an assay limit of detection. When concentration levels fall below the limit, exact measures cannot be obtained, and thus are left censored. The problem becomes more challenging when the censored data come from heterogeneous populations consisting of exposed and non-exposed subjects. If the censored data come from non-exposed subjects, their measures are always zero and hence censored, forming a latent class governed by a distinct censoring mechanism compared with the exposed subjects. The exposed group's censored measurements are always greater than zero, but less than the detection limit. It is very often that the exposed and non-exposed subjects may have different disease traits or different relationships with outcomes of interest, so we need to disentangle the two different populations for valid inference. In this article, we aim to fill the methodological gaps in the literature by developing a novel joint modeling approach to not only address the censoring issue in predictors, but also untangle different relationships of exposed and non-exposed subjects with the outcome. Simulation studies are performed to assess the numerical performance of our proposed approach when the sample size is small to moderate. The joint modeling approach is also applied to examine associations between plasma metabolites and blood pressure in Bogalusa Heart Study, and identify new metabolites that are highly associated with blood pressure.


Assuntos
Modelos Estatísticos , Humanos , Limite de Detecção , Simulação por Computador , Estudos Longitudinais
7.
Stat Med ; 43(1): 102-124, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-37921025

RESUMO

Human microbiome research has gained increasing importance due to its critical roles in comprehending human health and disease. Within the realm of microbiome research, the data generated often involves operational taxonomic unit counts, which can frequently present challenges such as over-dispersion and zero-inflation. To address dispersion-related concerns, the generalized Poisson model offers a flexible solution, effectively handling data characterized by over-dispersion, equi-dispersion, and under-dispersion. Furthermore, the realm of zero-inflated generalized Poisson models provides a strategic avenue to simultaneously tackle both over-dispersion and zero-inflation. The phenomenon of zero-inflation frequently stems from the heterogeneous nature of study populations. It emerges when specific microbial taxa fail to thrive in the microbial community of certain subjects, consequently resulting in a consistent count of zeros for these individuals. This subset of subjects represents a latent class, where their zeros originate from the genuine absence of the microbial taxa. In this paper, we introduce a novel testing methodology designed to uncover such latent classes within generalized Poisson regression models. We establish a closed-form test statistic and deduce its asymptotic distribution based on estimating equations. To assess its efficacy, we conduct an extensive array of simulation studies, and further apply the test to detect latent classes in human gut microbiome data from the Bogalusa Heart Study.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Modelos Estatísticos , Simulação por Computador , Estudos Longitudinais , Distribuição de Poisson
8.
Acta Pharmacol Sin ; 45(6): 1201-1213, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38491160

RESUMO

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.


Assuntos
Via de Sinalização Hippo , Interleucina-6 , Regeneração Hepática , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases , Receptor Tipo 2 de Angiotensina , Transdução de Sinais , Animais , Masculino , Camundongos , Acetaminofen , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Interleucina-6/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/fisiologia , Camundongos Knockout , Proteínas Serina-Treonina Quinases/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Proteínas de Sinalização YAP/metabolismo
9.
Opt Express ; 31(23): 37564-37573, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017883

RESUMO

A hole-assisted three-core fiber (HATCF) has been proposed as a sensor for simultaneous measurement of refractive index (RI) and temperature. An 8 mm long HATCF is fused between two single mode fibers (SMFs). One air hole of the HATCF is opened by femtosecond laser ablation technique to expose a suspended core to the external environment. Due to the same diameters of the two suspended cores, the resonance couplings between the center core and the two suspended cores occur at the same wavelength, which leads to a strong resonance dip. When the solution is filled into the open air hole, the resonance dip is split in two dips because the phase matching wavelength between center core and the suspended core in the open air hole is changed. Simultaneous measurement of RI and temperature can be achieved by monitoring the wavelengths of the two dips. The measured RI and temperature sensitivities are 1369 nm/RIU in the range of 1.333-1.388 and 83.48 pm/°C in the range of 25-70 °C. The proposed sensor has outstanding advantages such as simple structure, high integration and dual parameter measurement, making it a potential application in the field of biological detection.

10.
Opt Express ; 31(20): 32543-32553, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859055

RESUMO

An optical fiber sensor based on a hole-assisted dual-core fiber (HADCF) has been proposed and experimentally demonstrated for dual-parameter measurements. The dual-mode interferometer created uses the LP01 mode and LP11 mode in the suspended core of a specialist optical fiber, combined with a directional coupler formed by using the suspended core and the center core in a 16 mm long HADCF. Using this, the simultaneous measurement of salinity (due to the presence of NaCl) and temperature has been achieved through monitoring the interference dip and resonance dip. The sensitivities of the measurement of salinity and temperature are 190.7 pm/‰ and -188.2 pm/°C, respectively. The sensor developed has the advantages of simplicity of fabrication, a high level of integration and the potential for measurement of dual parameters, supporting its potential applications in marine environment measurements.

11.
Opt Lett ; 48(17): 4574-4577, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656558

RESUMO

This Letter proposes a method that balances miniaturization and high performance of fiber optic speckle spectrometers. The periodically tapered coreless fiber is used as the scattering element to excite more higher-order modes in the coreless fiber. As a result, a remarkable spectral resolution of 0.03 nm in the near-infrared spectrum can be achieved with a 5-cm-long fiber. Narrow linewidth and broadband spectra in the wavelength of 1540-1560 nm are reconstructed separately, demonstrating the excellent performance of the designed all-fiber spectrometer. The spectral resolution of our proposed spectrometer is comparable to that of a 2-m multimode fiber spectrometer and has a significant improvement in miniaturization.

12.
Phys Rev Lett ; 130(21): 216704, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37295077

RESUMO

Gapped fracton phases of matter generalize the concept of topological order and broaden our fundamental understanding of entanglement in quantum many-body systems. However, their analytical or numerical description beyond exactly solvable models remains a formidable challenge. Here we employ an exact 3D quantum tensor-network approach that allows us to study a Z_{N} generalization of the prototypical X cube fracton model and its quantum phase transitions between distinct topological states via fully tractable wave function deformations. We map the (deformed) quantum states exactly to a combination of a classical lattice gauge theory and a plaquette clock model, and employ numerical techniques to calculate various entanglement order parameters. For the Z_{N} model we find a family of (weakly) first-order fracton confinement transitions that in the limit of N→∞ converge to a continuous phase transition beyond the Landau-Ginzburg-Wilson paradigm. We also discover a line of 3D conformal quantum critical points (with critical magnetic flux loop fluctuations) which, in the N→∞ limit, appears to coexist with a gapless deconfined fracton state.

13.
Org Biomol Chem ; 21(7): 1389-1394, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36655625

RESUMO

We report herein a cationic iridium-catalysed thioether-directed alkyne-azide cycloaddition reaction. Diverse 2-alkynyl phenyl sulfides can undergo cycloaddition with different azides in a regioselective fashion. The reaction features high efficiency, a short reaction time, and a broad substrate scope, providing modular access to complex S-containing triazoles.

14.
Org Biomol Chem ; 21(45): 8979-8983, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37934046

RESUMO

The synthesis of stereo-defined α-trifluoromethyl arylenes is of great importance in medical chemistry, organic chemistry, and materials science. However, despite the recent advances, the Z-selective formation of α-trifluoromethyl arylenes has remained underdeveloped. Here, we describe a facile approach towards Z-α-trifluoromethyl arylenes through Pd-catalysed stereoselective fluoroarylation of 1,1-difluoroallenes in the presence of a bulky monophosphine ligand.

15.
Artigo em Inglês | MEDLINE | ID: mdl-37256417

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by continuous constriction and occlusion of small pulmonary arteries, leading to the development of right ventricular failure and death. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a kind of serine protease enzyme that increases low-density lipoprotein cholesterol (LDLC) levels through degrading low-density lipoprotein cholesterol receptors (LDLr). However, whether inhibition of PCSK9 can alleviate PAH has not been reported. METHODS AND RESULTS: We reported that PCSK9 expression was up-regulated in lung tissues of PAH patients. In addition, we used PCSK9 monoclonal antibody subcutaneously to inhibit PCSK9 expression in mice exposed to chronic hypoxia (10%) in combination with SU5416, a VEGF receptor inhibitor. Hypoxia plus SU5416-induced PAH was attenuated in PCSK9 monoclonal antibody-treated mice compared with wild-type mice. PCSK9 inhibited pulmonary vascular remodeling in mice. Moreover, PCSK9 knockdown significantly altered the proliferation and migration of hypoxia-induced PASMCs. We also found that PCSK9 monoclonal antibody inhibited Notch3 expression in vivo and in vitro. CONCLUSION: Our results suggest that the PCSK9-Notch3 signaling pathway is critical for the proliferation and migration of PASMCs and provides a potential drug target for the treatment of PAH.

16.
BMC Endocr Disord ; 23(1): 181, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37641098

RESUMO

BACKGROUND: Marine Lenhart syndrome is a rare disease and causes refractory hyperthyroidism. So far, little evidence on the combination of both Marine Lenhart syndrome and Hashimoto's thyroiditis is available. We suspect that Marine Lenhart syndrome when combined with Hashimoto's thyroiditis might have its particular features, which are not exactly the same as those of the isolated Marine Lenhart syndrome. CASE PRESENTATION: A 56-year-old middle-aged man presented with recurrent hyperthyroidism, and Graves' disease combined with Hashimoto's thyroiditis was considered. Radionuclide imaging showed a hot nodule, but ultrasonography suggested the possibility of malignancy with a category of 4B according to the Chinese-Thyroid Imaging-Reporting and Data System (C-TIRADS) model. Fine needle aspiration cytology (FNAC) revealed eosinophilic follicular lesions with papillary features, and prompted that papillary thyroid carcinoma could not be excluded. Partial thyroidectomy was performed and the nodule was proven to be benign by histopathology. The final diagnosis was atypical Marine Lenhart syndrome with Hashimoto's thyroiditis. CONCLUSIONS: Marine Lenhart syndrome combined with Hashimoto's thyroiditis has its particular characteristics, showing some signs mimicking malignancy. Limitations of ultrasonography and FNAC in diagnosis should be noted in these scenarios.


Assuntos
Doença de Graves , Doença de Hashimoto , Hipertireoidismo , Neoplasias da Glândula Tireoide , Masculino , Pessoa de Meia-Idade , Humanos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Doença de Hashimoto/complicações , Doença de Hashimoto/diagnóstico , Câncer Papilífero da Tireoide/diagnóstico , Síndrome
17.
PLoS Genet ; 16(4): e1008693, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32324833

RESUMO

Amino acids exert many biological functions, serving as allosteric regulators and neurotransmitters, as constituents in proteins and as nutrients. GCN2-mediated phosphorylation of eukaryotic initiation factor 2 alpha (elF2α) restores homeostasis in response to amino acid starvation (AAS) through the inhibition of the general translation and upregulation of amino acid biosynthetic enzymes and transporters by activating the translation of Gcn4 and ATF4 in yeast and mammals, respectively. GCN1 is a GCN2-binding protein that possesses an RWD binding domain (RWDBD) in its C-terminus. In yeast, Gcn1 is essential for Gcn2 activation by AAS; however, the roles of GCN1 in mammals need to be established. Here, we revealed a novel role of GCN1 that does not depend on AAS by generating two Gcn1 mutant mouse lines: Gcn1-knockout mice (Gcn1 KO mice (Gcn1-/-)) and RWDBD-deleted mutant mice (Gcn1ΔRWDBD mice). Both mutant mice showed growth retardation, which was not observed in the Gcn2 KO mice, such that the Gcn1 KO mice died at the intermediate stage of embryonic development because of severe growth retardation, while the Gcn1ΔRWDBD embryos showed mild growth retardation and died soon after birth, most likely due to respiratory failure. Extension of pregnancy by 24 h through the administration of progesterone to the pregnant mothers rescued the expression of differentiation markers in the lungs and prevented lethality of the Gcn1ΔRWDBD pups, indicating that perinatal lethality of the Gcn1ΔRWDBD embryos was due to simple growth retardation. Similar to the yeast Gcn2/Gcn1 system, AAS- or UV irradiation-induced elF2α phosphorylation was diminished in the Gcn1ΔRWDBD mouse embryonic fibroblasts (MEFs), suggesting that GCN1 RWDBD is responsible for GCN2 activity. In addition, we found reduced cell proliferation and G2/M arrest accompanying a decrease in Cdk1 and Cyclin B1 in the Gcn1ΔRWDBD MEFs. Our results demonstrated, for the first time, that GCN1 is essential for both GCN2-dependent stress response and GCN2-independent cell cycle regulation.


Assuntos
Ciclo Celular , Proliferação de Células , Desenvolvimento Fetal , Proteínas de Ligação a RNA/metabolismo , Estresse Fisiológico , Transativadores/metabolismo , Animais , Proteína Quinase CDC2/metabolismo , Células Cultivadas , Ciclina B1/metabolismo , Fibroblastos/metabolismo , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ligação a RNA/genética , Transativadores/genética
18.
BMC Med Educ ; 23(1): 794, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880665

RESUMO

BACKGROUND: Intraspinal anesthesia poses significant teaching challenges and inadequate teaching resources, which ultimately limit students' opportunities for practice. To address this issue, we aimed to develop a virtual platform for combined spinal-epidural anesthesia that merges virtual reality technology with haptic feedback technology, while assessing its educational impact and learning outcomes. METHODS: We utilized MIMICS, 3Ds MAX, and UNITY 3D software to perform 3D reconstruction based on lumbar CT/MRI data from a standard male volunteer. The haptic coefficients were configured on each layer by 20 experienced anesthesiologists in accordance with the Geomagic Touch X force feedback device. A total of 20 anesthesiology interns completed 30 virtual puncture training sessions. Two experienced anesthetists evaluated the efficacy of the platform and the level of mastery achieved using the Global Rating Scale (GRS) and a Checklist score, respectively. Finally, a questionnaire survey was conducted to gather feedback on the virtual platform. RESULTS: After the 10th session, the puncture time stabilized at 2.4 min. As the number of sessions increased, the Global Rating Scale (GRS) score stabilized by the 8th session, and the Checklist scores tended to stabilize by the 10th session. Results from questionnaires indicated that over half of the anesthesiology interns (70%) believed that the platform, which exhibited strong repeatability, improved their anatomical recognition and provided a strong sense of breakthrough in identifying the ligamentum flavum. The majority of them (80%) expressed satisfaction with the virtual platform. CONCLUSIONS: The platform effectively facilitated the acquisition of basic and accurate puncture skills on a virtual patient.


Assuntos
Anestesia Epidural , Realidade Virtual , Humanos , Masculino , Tecnologia Háptica , Software , Retroalimentação , Interface Usuário-Computador , Simulação por Computador
19.
BMC Med Educ ; 23(1): 546, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37528406

RESUMO

BACKGROUND: This meta-analysis was conducted to systematically evaluate the impact of problem-based learning (PBL) and lecture-based learning (LBL) teaching models on students' learning in surgical education. METHODS: We systematically searched the publications related to the application of PBL and LBL in surgical courses in PubMed, Embase, Web of Science and Cochrane Library databases, the last retrieval time is September 20, 2022. After screening the literature according to the inclusion and exclusion criteria, extracting data and evaluating the methodological treatment of the included studies, Stata 17.0 software was used to perform meta-analysis. RESULTS: Nine studies were included totally. The results showed that compared with LBL, PBL was superior in clinical competence (SMD = 0.81, 95% CI: 0.12 ~ 1.49, P = 0.020) and student satisfaction (SMD = 2.13, 95% CI: 1.11 ~ 3.15, P < 0.0001) with significant differences. But the comprehensive scores (SMD = 0.26, 95% CI: -0.37 ~ 0.89, P = 0.421) and theoretical knowledge (SMD=-0.19, 95% CI: -0.71 ~ 0.33, P = 0.482) to PBL and LBL had no significant difference. CONCLUSION: This study showed that the PBL teaching model is more effective than the LBL teaching model in surgical education on the aspects of enhancing clinical competence and student satisfaction. However, further well-designed studies are needed to confirm our findings.


Assuntos
Educação Médica , Aprendizagem Baseada em Problemas , Humanos , Aprendizagem Baseada em Problemas/métodos , Avaliação Educacional , Estudantes , Educação Médica/métodos , Competência Clínica
20.
J Pediatr Nurs ; 69: 1-5, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36584591

RESUMO

OBJECTIVE: To translate the English version Child Food Neophobia Scale (CFNS) into the Chinese version and test its reliability and validity in preschool children. METHODS: To create the Chinese version of the CFNS, it was translated, back-translated, and cross-culturally adapted. The use of the Chinese version of CFNS by 575 parents of preschool children in two kindergartens in Yangzhou City was investigated using cluster sampling to assess the reliability and validity of the scale. RESULTS: The Chinese version of CFNS has nine items in total. The scale-level average content validity index (S-CVI/Ave) is 0.983. Exploratory factor analysis (EFA) extracted 2 common factors, and the cumulative variance contribution rate was 49.437%. Confirmatory factor analysis (CFA) showed that the 2-factor model was well fitted. The Cronbach'α coefficient of the scale was 0.759, the Cronbach'α coefficients of the two factors were 0.735 and 0.713, the split-half reliability was 0.788, and the test-retest reliability was 0.756. CONCLUSION: The Chinese version of the Child Food Neophobia Scale has good reliability and validity in preschool children and can be used as an assessment tool for food neophobia in preschool children in China. PRACTICE IMPLICATIONS: This study has gone through a rigorous translation process, and the CFNS may support future exploration of food neophobia in preschool children. Food allergy factors in the results may be the next step in the research, and several studies are still needed to understand the relationship between food allergy and food neophobia.


Assuntos
Transtorno Alimentar Restritivo Evitativo , Pré-Escolar , Humanos , Transtorno Alimentar Restritivo Evitativo/diagnóstico , Transtorno Alimentar Restritivo Evitativo/etnologia , China , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Tradução , População do Leste Asiático , Comparação Transcultural
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