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1.
Anal Chem ; 96(29): 12022-12029, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-39001804

RESUMO

Disease diagnostics and surveillance increasingly highlight the importance of portable, cost-effective, and sensitive point-of-care (POC) detection of nucleic acids. Here, we report a CRISPR/Cas13a-responsive and RNA-bridged DNA hydrogel capillary sensor for the direct and visual detection of specific RNA with high sensitivity. The capillary sensor was simply prepared by loading RNA-cross-linking DNA hydrogel film (∼0.2 mm ± 0.02 mm) at the end of a capillary. When CRISPR/Cas13a specifically recognizes the target RNA, the RNA bridge in the hydrogel film is cleaved by the trans-cleavage activity of CRISPR/Cas13a, increasing the permeability of the hydrogel film. Different concentrations of target RNA activate different amounts of Cas13a, cleaving different amounts of the RNA bridge in the hydrogel and causing corresponding changes in the permeability of the hydrogel. Therefore, samples containing different amounts of the target RNA travel to different distances in the capillary. Visual reading of the distance provides quantitative detection of the RNA target without the need for any nucleic acid amplification or auxiliary equipment. The technique was successfully used for the determination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in clinical nasopharyngeal (NP) swab and saliva samples. Easily quantifiable distance using a ruler eliminates the need for any optical or electrochemical detection equipment, making this assay potentially useful for POC and on-site applications.


Assuntos
Sistemas CRISPR-Cas , DNA , Hidrogéis , SARS-CoV-2 , Humanos , Hidrogéis/química , DNA/química , DNA/análise , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , RNA Viral/análise , Técnicas Biossensoriais , COVID-19/diagnóstico , COVID-19/virologia , RNA/análise
2.
Chemphyschem ; 25(5): e202300693, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38183359

RESUMO

Lithium-sulfur batteries (LSBs) are considered as the development direction of the new generation energy storage system due to their high energy density and low cost. The slow redox kinetics of sulfur and the shuttle effect of lithium polysulfide (LiPS) are considered to be the main obstacles to the practical application of LSBs. Transition-metal sulfide as the cathode host can improve the Li-S redox chemistry. However, there has been no investigation of the application of FeS2 host in Li-S redox chemistry. Applying the first-principles calculations, we investigated the formation energy, band gap, Li+ diffusion, adsorption energy, catalytic performance and Li2 S decomposition barrier of FeAx S2-x (A=N, P, O, Se; x=0, 0.125, 0.25, 0.375) to explore the Li-S redox chemistry and finally select excellent host material. FeA0.25 S1.75 (A=P, Se) has a low Li+ diffusion barrier and superior electronic conductivity. FeO0.25 S1.75 is more favorable for LiPS adsorption, followed by FeP0.25 S1.75 . FeP0.25 S1.75 (001) shows a low overpotential for the Li-S redox chemistry. In summary, FeP0.25 S1.75 has more application potential in LSBs due to its physical and chemical properties, followed by FeSe0.25 S1.75 . This work provides theoretical guidance for the design and selection of the sulfur cathode host materials in LSBs.

3.
Phys Chem Chem Phys ; 26(3): 2249-2259, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38165279

RESUMO

Lithium-sulfur batteries (LSBs) are one of the most promising energy storage devices with high energy density. However, their application and commercialization are hampered by the slow Li-S redox chemistry. Fe0.875M0.125S2 (M = Ti, V), as the sulfur cathode host, enhances the Li-S redox chemistry. FeS2 with Pa3̄ is transformed into Li2FeS2 with P3̄m1 after discharge. The structure changes and physicochemical properties during Fe0.875M0.125S2 discharge process are further investigated to screen out the sulfur cathode host materials with the best comprehensive properties. The discharge structure of Fe0.875M0.125S2 is verified by the thermodynamic stability of Li-deficient phases, voltage and capacity based on Monte Carlo methods. Fe0.875M0.125S2 with Pa3̄ is transformed into Li2Fe0.875M0.125S2 with P3̄m1 after discharge. Using the first-principles calculations, the physicochemical properties of Li2Fe0.875M0.125S2 are systematically investigated, including the formation energy, voltage, theoretical capacity, electrical conductivity, Li+ diffusion, catalytic performance and Li2S oxidation decomposition. The average redox voltage of Li2Fe0.875V0.125S2 is higher than that of Li2Fe0.875Ti0.125S2. Li2Fe0.875M0.125S2 shows metallic properties. Li2Fe0.875V0.125S2 is more beneficial to the reduction reaction of Li2S2 and Li2S oxidation decomposition. Fe0.875V0.125S2 has more potential as the sulfur cathode host than Fe0.875Ti0.125S2 in LSBs. A new strategy for the selection of the sulfur cathode host material for LSBs is provided by this work.

4.
BMC Med Inform Decis Mak ; 24(1): 17, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225576

RESUMO

BACKGROUND: Heart failure is a syndrome with complex clinical manifestations. Due to increasing population aging, heart failure has become a major medical problem worldwide. In this study, we used the MIMIC-III public database to extract the temporal and spatial characteristics of electrocardiogram (ECG) signals from patients with heart failure. METHODS: We developed a NYHA functional classification model for heart failure based on a deep learning method. We introduced an integrating attention mechanism based on the CNN-LSTM-SE model, segmenting the ECG signal into 2 to 20 s long segments. Ablation experiments showed that the 12 s ECG signal segments could be used with the proposed deep learning model for superior classification of heart failure. RESULTS: The accuracy, positive predictive value, sensitivity, and specificity of the NYHA functional classification method were 99.09, 98.9855, 99.033, and 99.649%, respectively. CONCLUSIONS: The comprehensive performance of this model exceeds similar methods and can be used to assist in clinical medical diagnoses.


Assuntos
Aprendizado Profundo , Insuficiência Cardíaca , Humanos , Arritmias Cardíacas/diagnóstico , Eletrocardiografia/métodos , Insuficiência Cardíaca/diagnóstico , Bases de Dados Factuais , Algoritmos
5.
Sensors (Basel) ; 24(18)2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39338611

RESUMO

As artificially engineered subwavelength periodic structures, terahertz (THz) metasurface devices exhibit an equivalent dielectric constant and dispersion relation akin to those of natural materials with specific THz absorption peaks, describable using the Lorentz model. Traditional verification methods typically involve testing structural arrays using reflected and transmitted optical paths. However, directly detecting the dielectric constant of individual units has remained a significant challenge. In this study, we employed a THz time-domain spectrometer-based scattering-type scanning near-field optical microscope (THz-TDS s-SNOM) to investigate the near-field nanoscale spectrum and resonant mode distribution of a single-metal double-gap split-ring resonator (DSRR) and rectangular antenna. The findings reveal that they exhibit a dispersion relation similar to that of natural materials in specific polarization directions, indicating that units of THz metasurface can be analogous to those of molecular structures in materials. This microscopic analysis of the dispersion relation of artificial structures offers new insights into the working mechanisms of THz metasurfaces.

6.
BMC Nurs ; 23(1): 21, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183011

RESUMO

BACKGROUND: Postoperative pain control is pivotal for surgical care; it facilitates patient recovery. Although patient-controlled analgesia (PCA) has been available for decades, inadequate pain control remains. Nurses' knowledge of and attitude toward PCA may influence the efficacy on clinic application. PURPOSE: The purpose of this study is to evaluate nurses' knowledge of and attitude toward postoperative PCA and investigate the associated factors. METHODS: This is a cross-sectional study. We enrolled registered nurses from a 2200-bed medical center in northern Taiwan within one year. The participants completed an anonymous self-reported PCA knowledge inventory and PCA attitude inventory. Data were analyzed descriptively and associated were tested using logistic regression. RESULTS: With 303 participants enrolled, we discovered that nurses had limited knowledge of and a negative attitude toward PCA. Under half of the participants know how to set up a bolus dose and lockout intervals. The majority held misconceptions regarding side effect management for opioids. The minority agree to increase the dose when a patient experienced persistent pain or suggested the use of PCA. Surprisingly, participants with a bachelor's or master's degree had lower knowledge scores than those with a junior college degree. Those with 6-10 years of work experience also are lower than those with under 5 years of experience. However, the participants with experience of using PCA for patient care had higher knowledge scores and a more positive attitude. CONCLUSIONS: Although postoperative PCA has been available for decades and education programs are routinely provided, nurses had limited knowledge of and a negative attitude toward PCA. A higher education level and longer work experience were not associated with more knowledge. The current education programs on PCA should be revised to enhance their efficacy in delivering up-to-date knowledge and situation training which may convey supportive attitude toward clinical application of PCA.

7.
Analyst ; 148(22): 5605-5611, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37818948

RESUMO

Specific recognition and sensitive quantification of mRNA alternative splice variants have been a necessity for exploring the regulatory mechanism of RNA splicing and revealing the association between pre-mRNA splicing and transcriptome function, as well as disease diagnosis. However, their wide abundance range and high sequence homology pose enormous challenges for high sensitivity and selectivity quantification of splice variants. Herein, taking advantage of the excellent specificity of ligation and the powerful nucleic acid replication feature of loop-mediated isothermal amplification (LAMP), we developed a one-pot method (termed one-pot ligation-LAMP) for specific recognition and sensitive quantification of mRNA splicing variants based on two splicing junction-specific stem-loop DNA probe ligation and the subsequently initiating LAMP. The one-pot ligation-LAMP can specifically detect as low as 100 aM mRNA splice variants without any nonspecific signals and quantify them with a wide dynamics range spanning at least six orders of magnitude. We have demonstrated that the one-pot ligation-LAMP is a versatile and practical strategy for accurately quantifying different splicing variants in complex biological samples with high sensitivity all in one tube within 90 min, thereby providing an attractive tool for mRNA splice variant-related studies.


Assuntos
Técnicas de Amplificação de Ácido Nucleico , RNA Mensageiro/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Sondas de DNA , Sensibilidade e Especificidade
8.
Neurocase ; 29(6): 186-190, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38700142

RESUMO

Isolated fornix anterior column infarction has rarely been described and is difficult to assess accurately using conventional magnetic resonance imaging (MRI). We report the case of a 75-year-old female who experienced acute anterograde amnesia. MRI performed within 24 h after amnesia onset showed an isolated infarction of the bilateral anterior columns of the fornix on diffusion-weighted imaging (DWI). Her symptoms persisted for up to 50 days, and diffusion tensor imaging (DTI) showed disruption of the fiber tracts of the fornix. when acute amnesia syndrome onset, fornix anterior column infarction should be considered, and optimized DWI and DTI methods are needed to study the fornix in vivo in future research.


Assuntos
Imagem de Tensor de Difusão , Fórnice , Humanos , Feminino , Fórnice/diagnóstico por imagem , Fórnice/patologia , Idoso , Imagem de Difusão por Ressonância Magnética , Amnésia Anterógrada/etiologia , Amnésia/etiologia , Amnésia/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/complicações
9.
Phys Chem Chem Phys ; 25(12): 8515-8523, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36883530

RESUMO

All-solid-state lithium-sulfur batteries (ASSLSBs) have high reversible characteristics owing to the high redox potential, high theoretical capacity, high electronic conductivity, and low Li+ diffusion energy barrier in the cathode. Monte Carlo simulations with cluster expansion, based on the first-principles high-throughput calculations, predicted a phase structure change from Li2FeS2 (P3̄M1) to FeS2 (PA3̄) during the charging process. LiFeS2 is the most stable phase structure. The structure of Li2FeS2 after charging was FeS2 (P3̄M1). By applying the first-principles calculations, we explored the electrochemical properties of Li2FeS2 after charging. The redox reaction potential of Li2FeS2 was 1.64 to 2.90 V, implying a high output voltage of ASSLSBs. Flatter voltage step plateaus are important for improving the electrochemical performance of the cathode. The charge voltage plateau was the highest from Li0.25FeS2 to FeS2 and followed from Li0.375FeS2 to Li0.25FeS2. The electrical properties of LixFeS2 remained metallic during the Li2FeS2 charging process. The intrinsic Li Frenkel defect of Li2FeS2 was more conducive to Li+ diffusion than that of the Li2S Schottky defect and had the largest Li+ diffusion coefficient. The good electronic conductivity and Li+ diffusion coefficient of the cathode implied a better charging/discharging rate performance of ASSLSBs. This work theoretically verified the FeS2 structure after Li2FeS2 charging and explored the electrochemical properties of Li2FeS2.

10.
Environ Res ; 237(Pt 1): 116962, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37619634

RESUMO

It is of great significance to develop the effective technique to treat phenol-containing wastewater. Herein, Fe-based prussian blue analogues-derived zero valent iron (ZVI) was successfully synthesized by one-step calcination method. Owing to high specific surface area and rich active sites, ZVI-2 possessed excellent performance in charge transfer. Notably, in comparison with conventional ZVI and Fe2+, ZVI-2 can effectively activate peroxymonosulfate (PMS) for achieving rapid degradation of phenol, and the highest removal efficiency of phenol reached 94.9% within 24 min. More importantly, developed ZVI-2/PMS oxidation system with good stability displayed strong anti-interference capability. Interestingly, Fe0 loaded on the surface of ZVI-2 can efficiently break the O-O bond of PMS to generate reactive oxygen species (i.e., SO4•-, OH•, O2•- and 1O2). As main adsorption sites of PMS, the existence of oxygen vacancy promote the formation of high-valent transition metal complexes (namely ZVI-2≡Fe4+=O). Under the combined action of reactive oxygen species and ZVI-2≡Fe4+=O, phenol can be eventually degraded into CO2 and H2O. The possible degradation pathways of phenol were also investigated. Furthermore, proposed ZVI-2/PMS oxidation system displayed great potential for application in the field of wastewater treatment. All in all, current work provided a valuable reference for design and application of Fe-based catalysts in PS-AOPs.

11.
Mol Hum Reprod ; 28(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34904654

RESUMO

Infertility has become a global health issue, with the number of people suffering from the disease increasing year by year, and ART offering great promise for infertility treatment. However, the regulation of early embryonic development is complicated and a series of processes takes place, including the maternal-to-zygotic transition. In addition, developmental arrest is frequently observed during human early embryonic development. In this study, we performed single-cell RNA sequencing on a biopsied blastomere from human eight-cell embryos and tracked the developmental potential of the remaining cells. To compare the sequencing results between different eight-cell embryos, we have combined the research data of this project with the data previously shared in the database and found that cells from the same embryo showed a higher correlation. Additionally, the transcriptome of embryos with blastocyst formation failure was significantly different from developed embryos, and the gene expression as well as cell signaling pathways related to embryonic development were also altered. In particular, the expression of some maternal and zygotic genes in the failed blastocyst formation group was significantly altered: the overall expression level of maternal genes was significantly higher in the failed blastocyst than the developed blastocyst group. In general, these findings provide clues for the causes of human embryonic arrest after the eight-cell stage, and they also provide new ideas for improving the success rate of ART in clinical practice.


Assuntos
Blastocisto , Desenvolvimento Embrionário , Blastocisto/metabolismo , Blastômeros , Embrião de Mamíferos , Desenvolvimento Embrionário/genética , Feminino , Humanos , Gravidez , Análise de Sequência de RNA
12.
J Neurosci ; 40(19): 3862-3879, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32291328

RESUMO

Hydrocephalus is a pathologic condition associated with various brain diseases, including Alzheimer's disease (AD). Dysfunctional ependymal cells (EpCs) are believed to contribute to the development of hydrocephalus. It is thus of interest to investigate EpCs' development and function. Here, we report that vacuolar protein sorting-associated protein 35 (VPS35) is critical for EpC differentiation, ciliogenesis, and survival, and thus preventing neonatal hydrocephalus. VPS35 is abundantly expressed in EpCs. Mice with conditional knock-out (cKO) of Vps35 in embryonic (Vps35GFAP-Cre and Vps35Emx1-Cre) or postnatal (Vps35Foxj1-CreER) EpC progenitors exhibit enlarged lateral ventricles (LVs) and hydrocephalus-like pathology. Further studies reveal marked reductions in EpCs and their cilia in both Vps35GFAP-Cre and Vps35Foxj1-CreER mutant mice. The reduced EpCs appear to be due to impairments in EpC differentiation and survival. Additionally, both Vps35GFAP-Cre and Vps35Foxj1-CreER neonatal pups exhibit increased cell proliferation and death largely in a region close to LV-EpCs. Many microglia close to the mutant LV-EpC region become activated. Depletion of the microglia by PLX3397, an antagonist of colony-stimulating factor 1 receptor (CSF1R), restores LV-EpCs and diminishes the pathology of neonatal hydrocephalus in Vps35Foxj1-CreER mice. Taken together, these observations suggest unrecognized functions of Vps35 in EpC differentiation, ciliogenesis, and survival in neonatal LV, and reveal pathologic roles of locally activated microglia in EpC homeostasis and hydrocephalus development.SIGNIFICANCE STATEMENT This study reports critical functions of vacuolar protein sorting-associated protein 35 (VPS35) not only in promoting ependymal cell (EpC) differentiation, ciliogenesis, and survival, but also in preventing local microglial activation. The dysfunctional EpCs and activated microglia are likely to induce hydrocephalus.


Assuntos
Epêndima/metabolismo , Células Ependimogliais/metabolismo , Hidrocefalia/metabolismo , Microglia/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Animais Recém-Nascidos , Diferenciação Celular/fisiologia , Sobrevivência Celular , Epêndima/citologia , Hidrocefalia/fisiopatologia , Camundongos , Camundongos Knockout
13.
J Neurosci ; 40(38): 7355-7374, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32817249

RESUMO

17ß-Estradiol (E2) is produced from androgens via the action of the enzyme aromatase. E2 is known to be made in neurons in the brain, but the functions of neuron-derived E2 in the ischemic brain are unclear. Here, we used a forebrain neuron-specific aromatase KO (FBN-ARO-KO) mouse model to deplete neuron-derived E2 in the forebrain and determine its roles after global cerebral ischemia. We demonstrated that ovariectomized female FBN-ARO-KO mice exhibited significantly attenuated astrocyte activation, astrocytic aromatization, and decreased hippocampal E2 levels compared with FLOX mice. Furthermore, FBN-ARO-KO mice had exacerbated neuronal damage and worse cognitive dysfunction after global cerebral ischemia. Similar results were observed in intact male mice. RNA-seq analysis revealed alterations in pathways and genes associated with astrocyte activation, neuroinflammation, and oxidative stress in FBN-ARO-KO mice. The compromised astrocyte activation in FBN-ARO-KO mice was associated with robust downregulation of the astrocyte-derived neurotrophic factors, BDNF and IGF-1, as well as the astrocytic glutamate transporter, GLT-1. Νeuronal FGF2, which acts in a paracrine manner to suppress astrocyte activation, was increased in FBN-ARO-KO neurons. Interestingly, blocking FGF2 signaling by central injection of FGFR3-neutralizing antibody was able to reverse the diminishment in neuroprotective astrocyte reactivity, and attenuate neuronal damage in FBN-ARO-KO mice. Moreover, in vivo E2 replacement suppressed FGF2 signaling and rescued the compromised reactive astrogliosis and cognitive deficits. Collectively, our data provide novel genetic evidence for a beneficial role of neuron-derived E2 in astrocyte activation, neuroprotection, and cognitive preservation following ischemic injury to the brain.SIGNIFICANCE STATEMENT Following cerebral ischemia, astrocytes become highly reactive and can exert neuroprotection through the release of neurotrophic factors and clearance of neurotoxic glutamate. The current study advances our understanding of this process by demonstrating that neuron-derived 17ß-estradiol (E2) is neuroprotective and critical for induction of reactive astrocytes and their ability to produce astrocyte-derived neurotrophic factors, BDNF and IGF-1, and the glutamate transporter, GLT-1 after ischemic brain damage. These beneficial effects of neuron-derived E2 appear to be due, at least in part, to suppression of neuronal FGF2 signaling, which is a known suppressor of astrocyte activation. These findings suggest that neuron-derived E2 is neuroprotective after ischemic brain injury via a mechanism that involves suppression of neuronal FGF2 signaling, thereby facilitating astrocyte activation.


Assuntos
Astrócitos/metabolismo , Isquemia Encefálica/metabolismo , Estrogênios/metabolismo , Gliose/metabolismo , Neurônios/metabolismo , Comunicação Parácrina , Animais , Aromatase/genética , Aromatase/metabolismo , Isquemia Encefálica/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/metabolismo , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Transportador 2 de Aminoácido Excitatório/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos , Estresse Oxidativo
14.
J Am Chem Soc ; 143(43): 18287-18293, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34670366

RESUMO

A convenient enantioselective total synthesis of (+)-cyclobutastellettolide B via a strategy that involves a diastereoselective Johnson-Claisen rearrangement, a regioselective cyclopropoxytrimethylsilane ring-opening reaction, and a Norrish-Yang cyclization is described. The results of computational and experimental studies indicate that the regio- and stereoselectivity of the Norrish-Yang reaction are controlled by the C-H bond dissociation energy and restricted rotation of the C13-C14 bond.

15.
J Neurochem ; 156(6): 819-833, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32743804

RESUMO

Ganglioside GD3, a major ganglioside species in neural stem cells, plays a crucial role in maintenance of the self-renewal capacity of these cells. However, its bioactivity in postnatally differentiated neurons in the neurogenic regions of adult brains has not been elucidated. Here, we describe for the first time that deletion of GD3 not only impairs neurotrophin-induced stem cell proliferation, but also alters the dendritic structure as well as the number of synapses of nascent neurons in the dentate gyrus of adult brain. When examining the behavioral phenotypes, GD3 synthase-knockout (GD3S-KO) mice displayed impairment in hippocampus-dependent memory function. To further gain insight into its cellular function, we examined GD3-binding partners from mouse brain extract using a GD3-specific monoclonal antibody, R24, followed by LC-MS/MS analysis and identified a mitochondrial fission protein, the dynamin-related protein-1 (Drp1), as a novel GD3-binding protein. Biochemical and imaging analyses revealed mitochondrial fragmentation in GD3-depleted dentate gyrus neurons, suggesting that GD3 is essential for the mitochondrial Drp1 turnover that is required for efficient mitochondrial fission. These results suggest that GD3 is required for proper dendritic and spine maturation of newborn neurons in adult brain through the regulation of mitochondrial dynamics.


Assuntos
Dendritos/fisiologia , Gangliosídeos/fisiologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Mitocôndrias/fisiologia , Células-Tronco Neurais/fisiologia , Neurônios/fisiologia , Animais , Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais , Comportamento Animal , Cognição , Espinhas Dendríticas/fisiologia , Dinaminas/genética , Dinaminas/fisiologia , Gangliosídeos/antagonistas & inibidores , Gangliosídeos/genética , Transtornos da Memória/genética , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/ultraestrutura , Dinâmica Mitocondrial
16.
Opt Express ; 29(6): 8676-8684, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820310

RESUMO

Terahertz (THz) radiation from an inhomogeneous plasma filament generated by focusing two-color femtosecond laser pulses into argon gas filled in a chamber is investigated experimentally by tailoring the Gaussian pump laser beams with an iris, where broadband THz emission over 10 THz is produced. It is found that the collected far-field THz radiation includes not only coherent but also partial-coherent components of the THz waves, which are emitted from the different parts of the inhomogeneous plasma filament with different plasma densities, contributing correspondingly to the different frequencies of the THz spectrum. Our results suggest that the THz spectrum can be manipulated by controlling the plasma density distribution of the filaments.

17.
J Mol Cell Cardiol ; 138: 115-135, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783035

RESUMO

AIMS: There is a large subpopulation of multinucleated polyploid cardiomyocytes (M*Pc CMs) in the adult mammalian heart. However, the pathophysiological significance of increased M*Pc CMs in heart disease is poorly understood. We sought to determine the pathophysiological significance of increased M*Pc CMs during hypoxia adaptation. METHODS AND RESULTS: A model of hypoxia-induced cardiomyocyte (CM) multinucleation and polyploidization was established and found to be associated with less apoptosis and less reactive oxygen species (ROS) production. Compared to mononucleated diploid CMs (1*2c CMs), tetraploid CMs (4c CMs) exhibited better mitochondria quality control via increased mitochondrial autophagy (mitophagy). RNA-seq revealed Prkaa2, the gene for AMPKα2, was the most obviously up-regulated autophagy-related gene. Knockdown of AMPKα2 increased apoptosis and ROS production and suppressed mitophagy in 4c CMs compared to 1*2c CMs. Rapamycin, an autophagy activator, alleviated the adverse effect of AMPKα2 knockdown. Furthermore, silencing PINK1 also increased apoptosis and ROS in 4c CMs and weakened the adaptive superiority of 4c CMs. Finally, AMPKα2-/- mutant mice exhibited exacerbation of apoptosis and ROS production via decreases in AMPKα2-mediated mitophagy in 4c CMs compared to 1*2c CMs during hypoxia. CONCLUSIONS: Compared to 1*2c CMs, hypoxia-induced 4c CMs exhibited enhanced mitochondria quality control and less apoptosis via AMPKα2-mediated mitophagy. These results suggest that multinucleation and polyploidization allow CM to better adapt to stress via enhanced mitophagy. In addition, activation of AMPKα2 may be a promising target for myocardial hypoxia-related diseases.


Assuntos
Adaptação Fisiológica , Células Gigantes/patologia , Mitofagia , Miócitos Cardíacos/patologia , Poliploidia , Adenilato Quinase/metabolismo , Animais , Animais Recém-Nascidos , Apoptose , Hipóxia Celular , Inativação Gênica , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
18.
J Autoimmun ; 108: 102404, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31952907

RESUMO

The chromatin modifier enhancer of zeste homolog 2 (EZH2) methylates lysine 27 of histone H3 (H3K27) and regulates T cell differentiation. However, the potential role of EZH2 in the pathogenesis of rheumatoid arthritis (RA) remains elusive. We analyzed EZH2 expression in PBMC, CD4+ T cells, CD19+ B cell, and CD14+ monocytes from active treatment-naïve RA patients and healthy controls (HC). We also suppressed EZH2 expression using EZH2 inhibitor GSK126 and measured CD4+ T cell differentiation, proliferation and apoptosis. We further examined TGFß-SMAD and RUNX1 signaling pathways in EZH2-suppressed CD4+ T cells. Finally, we explored the regulation mechanism of EZH2 by RA synovial fluid and fibroblast-like synoviocyte (FLS) by neutralizing key proinflammatory cytokines. EZH2 expression is lower in PBMC and CD4+ T cells from RA patients than those from HC. EZH2 inhibition suppressed regulatory T cells (Tregs) differentiation and FOXP3 transcription, and downregulated RUNX1 and upregulated SMAD7 expression in CD4+ T cells. RA synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4+ T cells, which was partially neutralized by anti-IL17 antibody. Taken together, EZH2 in CD4+ T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4+ T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4+ T cells. Defective EZH2 in CD4+ T cells might contribute to Treg deficiency in RA.


Assuntos
Artrite Reumatoide/etiologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Proteína Potenciadora do Homólogo 2 de Zeste/deficiência , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , Estudos de Casos e Controles , Citocinas/metabolismo , Histonas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Líquido Sinovial/imunologia , Líquido Sinovial/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/citologia
19.
Phys Chem Chem Phys ; 22(26): 14694-14703, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32573573

RESUMO

The influence of temperature and Al content on the segregation and homogenization behaviour of In-Al atoms in CuIn1-xAlxSe2 (CIAS) pseudobinary alloys is studied using a combination of cluster expansion Monte Carlo simulations and first-principles calculations. Such alloys are promising materials for a number of solar-energy-related applications. We found that the segregation of In-Al atoms in CIAS alloys with different Al contents occurs at relatively low temperatures. The cluster morphology of Al(In) atoms in CIAS alloys at 73 K appears in an ellipsoidal, rod-like or lamellar form, depending on the Al(In) content. The spatial distribution of In-Al atoms becomes homogeneous as the temperature increases. By determining the inhomogeneity degree σ of In-Al distributions in CIAS alloys at a series of temperatures, we found that the variation of σ with temperature (T) for all the considered CIAS alloys are sigmoidal in general and the sharp decrease in σ within a certain temperature range implies the occurrence of inhomogeneous-to-homogeneous phase transition. The inhomogeneity degree σ of CIAS alloys before or after the phase transition (phase segregation) increases as the content of Al(x) and In(1 - x) atoms gets closer. The σ(T) data points obtained by us can be well fitted with the Boltzmann function, which can give several physically meaningful parameters such as the phase transition temperature T0, temperature range of phase transition ΔT and so on. The fitted T0 and ΔT values for CIAS alloys with different Al content were proved to be reliable. The novel method for predicting the T0 and ΔT may be applied to many other binary or pseudobinary material systems with positive formation energy.

20.
Gastroenterol Hepatol ; 43(10): 598-606, 2020 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32674880

RESUMO

OBJECTIVE: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play important regulatory roles in the tumorigenesis and progression of gastric cancer (GC). The aim of this study was to construct the prognostic predictive model of lncRNAs signature and improve the survival prediction of GC. PATIENTS AND METHODS: The expression profiling of lncRNAs in large GC cohorts was performed from The Cancer Genome Atlas (TCGA) databases using the lncRNAs-mining approach, including training data set (N=160) and testing data set (N=159). A 13-lncRNAs signature significantly associated with overall survival (OS) in the training data set was selected. The prognostic value of this 13-lncRNAs signature was then confirmed in the test validation set and the entire validation set, respectively. RESULTS: Based on lncRNA expression profiling of 319 patients with stomach adenocarcinoma (STAD), prognostic 13-lncRNAs signature was found to be significantly associated with the prognosis of GC. Compared to patients with low-risk scores, patients with high-risk scores had a significantly shorter survival time. Moreover, functional enrichment analysis indicated that this 13-lncRNAs signature was potentially involved in multiple biological processes, such as DNA replication and cell cycle signaling pathway. CONCLUSIONS: The prognostic model of the 13-lncRNAs signature established by our study could improve the survival prediction of GC to a greater extent.


Assuntos
Adenocarcinoma/mortalidade , RNA Longo não Codificante/análise , RNA-Seq , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Ciclo Celular/genética , Replicação do DNA , Bases de Dados Genéticas , Progressão da Doença , Feminino , Marcadores Genéticos , Humanos , Masculino , Prognóstico , Análise de Regressão , Fatores de Risco , Transdução de Sinais/genética , Neoplasias Gástricas/patologia , Análise de Sobrevida
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