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1.
Bioconjug Chem ; 35(8): 1166-1171, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39046902

RESUMO

Programmed DNA structures and assemblies are readily accessible, but site-specific functionalization is critical to realize applications in various fields such as nanoelectronics, nanomaterials and biomedicine. Besides pre- and post-DNA synthesis conjugation strategies, on-solid support reactions offer advantages in certain circumstances. We describe on-solid support internucleotide coupling reactions, often considered undesirable, and a workaround strategy to overcome them. Palladium coupling reactions enabled on-solid support intra- and interstrand coupling between single-stranded DNAs (ss-DNAs). Dilution with a capping agent suppressed interstrand coupling, maximizing intrastrand coupling. Alternatively, interstrand coupling actually proved advantageous to provide dimeric organic/DNA conjugates that could be conveniently separated from higher oligomers, and was more favorable with longer terphenyl coupling partners.


Assuntos
Paládio , Paládio/química , DNA/química , DNA de Cadeia Simples/química
2.
Langmuir ; 40(1): 614-623, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38150370

RESUMO

Solar-energy-driven CO2 hydrogenation is a promising strategy to alleviate the climate crisis. Methane is a desirable derivative of CO2 reduction. However, developing a photocatalyst for highly active and selective CH4 generation remains challenging. Herein, we report a double Z-scheme Bi3O4Cl/g-C3N4/Cd0.5Zn0.5S photocatalyst for efficient reduction of CO2 to CH4. In situ characterization techniques confirmed that the charge migration mechanism in Bi3O4Cl/g-C3N4/Cd0.5Zn0.5S promotes charge separation through double internal electric fields. As a result, the optimized C0.01B0.02C catalyst displayed a formation rate high up to 25.34 µmol g-1 h-1 and a selectivity of 96.52% of CH4. Moreover, the AQY of CO2 conversion on C0.01B0.02C (1.84%) was almost 41 times higher than that of the bare CN. This study provides a novel perspective to develop heterojunction photocatalysts for selective CO2 conversion to CH4.

3.
J Am Chem Soc ; 145(32): 17945-17953, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37530628

RESUMO

Metal-mediated DNA (mmDNA) presents a pathway toward engineering bioinorganic and electronic behavior into DNA devices. Many chemical and biophysical forces drive the programmable chelation of metals between pyrimidine base pairs. Here, we developed a crystallographic method using the three-dimensional (3D) DNA tensegrity triangle motif to capture single- and multi-metal binding modes across granular changes to environmental pH using anomalous scattering. Leveraging this programmable crystal, we determined 28 biomolecular structures to capture mmDNA reactions. We found that silver(I) binds with increasing occupancy in T-T and U-U pairs at elevated pH levels, and we exploited this to capture silver(I) and mercury(II) within the same base pair and to isolate the titration points for homo- and heterometal base pair modes. We additionally determined the structure of a C-C pair with both silver(I) and mercury(II). Finally, we extend our paradigm to capture cadmium(II) in T-T pairs together with mercury(II) at high pH. The precision self-assembly of heterobimetallic DNA chemistry at the sub-nanometer scale will enable atomistic design frameworks for more elaborate mmDNA-based nanodevices and nanotechnologies.


Assuntos
Mercúrio , Prata , Pareamento de Bases , Prata/química , DNA/química , Mercúrio/química
4.
Small ; 19(48): e2303632, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37541658

RESUMO

Covalent organic frameworks (COFs) are one type of porous organic materials linked by covalent bonds. COFs materials exhibit many outstanding characteristics such as high porosity, high chemical and thermal stability, large specific surface area, efficient electron transfer efficiency, and the ability for predesigned structures. These exceptional advantages enable COFs materials to exhibit remarkable performance in photocatalysis. Additionally, the activity of COFs materials as photocatalysts can be significantly upgraded by ion doping and the formation of heterojunctions. This paper summarizes the latest research progress on COF-based materials applied in photocatalytic systems. Initially, typical structures and preparation methods of COFs are analyzed and compared. Moreover, the essential principles of photocatalytic reactions over COFs-based materials and the latest research developments in photocatalytic hydrogen production, CO2 reduction, pollutants elimination, organic transformation, and overall water splitting are indicated. At last, the outlook and challenges of COF-based materials in photocatalysis are discussed. This review is intended to permit instructive guidance for the efficient use of photocatalysis based on COFs in the future.

5.
Small ; 19(22): e2300460, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36855324

RESUMO

Photocatalysis driven by solar energy is a feasible strategy to alleviate energy crises and environmental problems. In recent years, significant progress has been made in developing advanced photocatalysts for efficient solar-to-chemical energy conversion. Single-atom catalysts have the advantages of highly dispersed active sites, maximum atomic utilization, unique coordination environment, and electronic structure, which have become a research hotspot in heterogeneous photocatalysis. This paper introduces the potential supports, preparation, and characterization methods of single-atom photocatalysts in detail. Subsequently, the fascinating effects of single-atom photocatalysts on three critical steps of photocatalysis (the absorption of incident light to produce electron-hole pairs, carrier separation and migration, and interface reactions) are analyzed. At the same time, the applications of single-atom photocatalysts in energy conversion and environmental protection (CO2 reduction, water splitting, N2 fixation, organic macromolecule reforming, air pollutant removal, and water pollutant degradation) are systematically summarized. Finally, the opportunities and challenges of single-atom catalysts in heterogeneous photocatalysis are discussed. It is hoped that this work can provide insights into the design, synthesis, and application of single-atom photocatalysts and promote the development of high-performance photocatalytic systems.

6.
Small ; 19(19): e2207875, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36772913

RESUMO

Converting CO2 into value-added products by photocatalysis, electrocatalysis, and photoelectrocatalysis is a promising method to alleviate the global environmental problems and energy crisis. Among the semiconductor materials applied in CO2 catalytic reduction, Cu2 O has the advantages of abundant reserves, low price and environmental friendliness. Moreover, Cu2 O has unique adsorption and activation properties for CO2 , which is conducive to the generation of C2+ products through CC coupling. This review introduces the basic principles of CO2 reduction and summarizes the pathways for the generation of C1 , C2 , and C2+ products. The factors affecting CO2 reduction performance are further discussed from the perspective of the reaction environment, medium, and novel reactor design. Then, the properties of Cu2 O-based catalysts in CO2 reduction are summarized and several optimization strategies to enhance their stability and redox capacity are discussed. Subsequently, the application of Cu2 O-based catalysts in photocatalytic, electrocatalytic, and photoelectrocatalytic CO2 reduction is described. Finally, the opportunities, challenges and several research directions of Cu2 O-based catalysts in the field of CO2 catalytic reduction are presented, which is guidance for its wide application in the energy and environmental fields is provided.

7.
Small ; 19(38): e2301892, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37194985

RESUMO

Photocatalytic CO2 reduction to valuable fuels is a promising way to alleviate anthropogenic CO2 emissions and energy crises. Perovskite oxides have attracted widespread attention as photocatalysts for CO2 reduction by virtue of their high catalytic activity, compositional flexibility, bandgap adjustability, and good stability. In this review, the basic theory of photocatalysis and the mechanism of CO2 reduction over perovskite oxide are first introduced. Then, perovskite oxides' structures, properties, and preparations are presented. In detail, the research progress on perovskite oxides for photocatalytic CO2 reduction is discussed from five aspects: as a photocatalyst in its own right, metal cation doping at A and B sites of perovskite oxides, anion doping at O sites of perovskite oxides and oxygen vacancies, loading cocatalyst on perovskite oxides, and constructing heterojunction with other semiconductors. Finally, the development prospects of perovskite oxides for photocatalytic CO2 reduction are put forward. This article should serve as a useful guide for creating perovskite oxide-based photocatalysts that are more effective and reasonable.

8.
Opt Lett ; 48(21): 5551-5554, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910700

RESUMO

The next-generation diffraction grating not only requires a nonmechanical control and a remote control to generate a diffraction pattern but also requires a tunable period. Here, we propose a stimuli-responsive liquid crystal (LC) phase grating with a tunable period and a diffraction order. The stimuli-responsive LC diffraction grating is composed of periodically arranged electrodes on a double-sided glass substrate. By adjusting the driving scheme, the pitch and diffraction order of the LC grating can be switched between three different modes. The experimental results show that the LC grating has a lower driving voltage (∼5 V). In addition, the tunable LC grating can achieve more diffraction orders, which can be applied to a holographic display to achieve a wide-viewing angle and an enlarged size.

9.
Anal Chem ; 94(33): 11650-11658, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35926115

RESUMO

We report a segmented spectrum scan method using Orbitrap MS in chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) for improving the metabolite detection efficiency. In this method, the full m/z range is divided into multiple segments with the scanning of each segment to produce multiple narrow-range spectra during the LC data acquisition. These segmented spectra are separately processed to extract the peak pair information with each peak pair arising from a differentially labeled metabolite in the analysis of a mixture of 13C and 12C reagent-labeled samples. The sublists of peak pairs are merged to form the final peak pair list from the LC-MS run. Various experimental conditions, including automatic gain control (AGC) values, mass resolutions, segment m/z widths, number of segments, and total data acquisition time in the LC run, were examined to arrive at an optimal setting in the segment scan for increasing the number of detectable metabolites while maintaining the same analysis time as in the full scan. The optimal method used a segment width of 120 m/z with 60k resolution for a 16 min CIL LC-MS run. Using dansyl-labeled human urine samples as an example, we demonstrated that this method could detect 5867 peak pairs or metabolites (not features), compared to 3765 peak pairs detectable in a full scan, representing a 56% gain. Out of 5867 peak pairs, 5575 (95.0%) could be identified or mass-matched. The relative quantification accuracy was slightly reduced (81% peak pairs were within ±25% of the expected peak ratio of 1.0 in full, compared to 87% in the full scan) due to the inclusion of more low-abundance peak pairs in the segment scan. The peak ratio measurement precision was not significantly affected by the segment scan. We also showed the increase of the peak pair number detectable from 3843 in the full scan to 7273 (89% gain) using the Orbitrap operated at 120k resolution with a 60 m/z segment width when multiple repeat sample injections were used. Thus, segment scan Orbitrap MS is an enabling method for detecting coeluting metabolites in CIL LC-MS for increasing the metabolomic coverage.


Assuntos
Compostos de Dansil , Marcação por Isótopo , Humanos , Isótopos de Carbono/química , Cromatografia Líquida/métodos , Compostos de Dansil/química , Marcação por Isótopo/métodos , Espectrometria de Massas/métodos , Metaboloma , Metabolômica/métodos
10.
Opt Express ; 30(21): 37946-37956, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36258373

RESUMO

A fast response electrically controlled liquid crystal (LC) lens array is revealed. In order to realize the fast response, a double LC layer structure is adopted. The fabricated LC lens array has a small pitch of 310µm and LC layer with a thickness of 50µm. Experimental results show that the focal length of the LC lens array can be continuously adjusted by low driving voltage (∼6.5Vrms), and the shortest focal length is 0.5mm. The switching between 2D display and 3D display is realized by controlling the voltage off and on state of the LC lens array. Experimental result shows that the 2D/3D switchable display has a fast response time of 16ms. The short pitch LC lens array is expected to be used in high-resolution 2D/3D switchable display.

11.
Opt Lett ; 47(15): 3664-3667, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913284

RESUMO

A liquid crystal (LC) lenticular lens array with auxiliary electrodes is proposed. The introduction of the auxiliary electrodes helps to obtain an LC lens array (LCLA) with relatively large aperture without complex structures. When the LCLA is in the focusing state, the voltage of auxiliary electrodes is less than that of edge electrodes, and the generated electric field in the LCLA can penetrate into the LC layer. Therefore, the ideal phase profile is obtained with a relatively thin LC layer thickness. Experimental results show that the LCLA has the characteristics of high optical power and low operation voltage. Based on the proposed LCLA, a multi-view 2D/3D switchable display is realized. In the experiment, a series of parallax images is obtained by rotating the sample to replace the convergence shooting method for 3D imaging. Compared with other 2D/3D switchable display devices, the multi-view 2D/3D switchable display based on the LCLA is characterized by being thin and compact, and displaying no moiré pattern.

12.
Soft Matter ; 18(17): 3328-3334, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35385566

RESUMO

In this work, we investigate the three-dimensional lattice deformation of blue phase (BP) liquid crystals under electrostriction. Using the in situ measurement of light diffraction signals from a twinned crystal, we propose a method to experimentally determine the lattice constants of BPs under an electric field; the overlap angle in the diffraction pattern of BP twinning domains gives the ratio of lattice constants in the lateral direction of the field, which can be analyzed together with the Bragg reflection peak wavelength along the field direction to yield three-dimensional lattice constants. The obtained values are confirmed to show good agreement with the diffraction data measured from a converging monochromatic light. Furthermore, by applying the method to BPs in a thin cell and specifying the transitions of azimuthal orientation, three-dimensional lattice deformation of BP I crystals and evolution of the azimuthal orientation are clarified under the electrostriction. Results reveal that the BPs confined to thin films undergo discrete elongation along the field direction and the BP I crystal undergoes larger lattice deformation in the field-perpendicular directions than that along the field. Our work allows a relatively easy determination of three-dimensional lattice constants of deformed BP crystals under an electric field, and the obtained results provide important insights into the understanding of the electrostriction behaviour of BPs towards improvement of the electro-optical performance of BP devices in practical applications.

13.
J Card Surg ; 37(5): 1319-1327, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35170791

RESUMO

BACKGROUND AND AIM OF THE STUDY: Whether minimally invasive mitral valve surgery (MMVS) leads to better outcomes remains unclear. We conducted a systematic review and meta-analysis comparing various MMVS approaches with conventional sternotomy. METHODS: We searched Cochrane CENTRAL, MEDLINE, EMBASE, ClinicalTrials. gov, and the ISRCTN Register for studies comparing minimally invasive approach (thoracotomy, port access, partial sternotomy, or robotic) with median sternotomy for mitral valve surgery. We performed title and abstract, full-text screening, and data extraction independently and in duplicate. We pooled data using random effect models. Quality assessment was performed using validated tools. Certainty of evidence was established using the GRADE framework. RESULTS: One hundred and nineteen studies (n = 38,106) met eligibility criteria: eight randomized controlled trials (RCTs) and 111 observational studies. MMVS was associated with fewer days in hospital (RCT: MD: -2.2 days, 95% CI, [-3.7 to -0.8]; observational: MD: -2.4 days, 95% CI, [-2.7 to -2.1]). Observational studies suggested that MMVS reduced transfusion requirements with fewer units transfused per patient (MD: -1.2; 95% CI, [-1.6 to -0.9]) and fewer patients transfused (RR, 0.7; 95% CI, [0.6-0.7]). Observational data also suggested lower mortality with MMVS (RR, 0.6; 95% CI, [0.5-0.7], p < .001, I2 = 0%), but this was not corroborated by RCT data. The risk of postoperative mitral regurgitation (≥2+ or requiring re-intervention) did not differ between the two groups. CONCLUSIONS: MMVS may be associated with shorter length of hospital stay with no significant difference in short-term morbidity and mortality. There is a paucity of high-quality data on the long-term outcomes of MMVS when compared with conventional sternotomy.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças das Valvas Cardíacas , Doenças das Valvas Cardíacas/cirurgia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Valva Mitral/cirurgia , Esternotomia , Resultado do Tratamento
14.
J Prosthet Dent ; 127(5): 703-708, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33441258

RESUMO

A digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery is presented. This technique integrates bone reduction and implant placement information into a dual-function surgical template and introduces a digital approach to fabricating immediate interim implant-supported fixed dental prostheses with the same occlusal relationship as the one evaluated with diagnostic removable prostheses.


Assuntos
Implantes Dentários , Carga Imediata em Implante Dentário , Prótese Dentária Fixada por Implante , Carga Imediata em Implante Dentário/métodos
15.
Sheng Li Xue Bao ; 74(4): 585-595, 2022 Aug 25.
Artigo em Zh | MEDLINE | ID: mdl-35993210

RESUMO

The purpose of this study was to establish a three-dimensional (3D) organoid culture system for type 2 alveolar epithelial (AT2) cells in mice. AT2 cells were isolated from ICR mouse lung and purified by enzymatic digestion and MicroBeads sorting. The purity of AT2 cells was determined by immunofluorescence (IF) staining using an antibody against proSPC. The AT2 differentiation was examined by IF staining with proSPC/HopX and proSPC/T1α antibodies, and proliferation of AT2 cells was assessed by EdU incorporation assays after two-dimensional (2D) culture for 8 days. In addition, AT2 cells were co-cultured with mouse lung fibroblasts (Mlg) in three-dimensional (3D) culture system. After 13 days of co-culture, the organoids were fixed in 2% paraformaldehyde for histological analysis and IF staining. The results showed that the purity of the AT2 cells was over 95%, as assessed by proSPC staining. 2D cultured AT2 cells were negative for EdU staining, which indicates that no proliferation occurs. proSPC expression was gradually disappeared, whereas T1α and HopX expression was gradually increased after 3, 5 and 8 days of culture. In 3D culture system, the alveolar organoids were formed after co-culturing AT2 cells with Mlg for 4 days. Histological analysis showed that alveolar organoids displayed a hollow morphology. proSPC was highly expressed in the peripheral cells, whereas type 1 alveolar epithelial (AT1) cells transdifferentiated from AT2 cells expressing HopX were mainly located in the interior of organoid bodies after 13 days. Some of the proSPC-positive AT2 cells located in the outer circle of alveolar organoids were stained positive for both proSPC and EdU, indicating that the AT2 cells in the alveolar organoids were proliferative. These results showed that the 3D organoid culture system of mouse AT2 cells was successfully established.


Assuntos
Células Epiteliais Alveolares , Organoides , Células Epiteliais Alveolares/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Células Epiteliais , Pulmão , Camundongos , Camundongos Endogâmicos ICR
16.
J Cell Mol Med ; 25(8): 4124-4135, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33624364

RESUMO

Thrombocytopenia is independently related with increased mortality in severe septic patients. Renin-angiotensin system (RAS) is elevated in septic subjects; accumulating studies show that angiotensin II (Ang II) stimulate the intrinsic apoptosis pathway by promoting reactive oxygen species (ROS) production. However, the mechanisms underlying the relationship of platelet apoptosis and RAS system in sepsis have not been fully elucidated. The present study aimed to elucidate whether the RAS was involved in the pathogenesis of sepsis-associated thrombocytopenia and explore the underlying mechanisms. We found that elevated plasma Ang II was associated with decreased platelet count in both patients with sepsis and experimental animals exposed to lipopolysaccharide (LPS). Besides, Ang II treatment induced platelet apoptosis in a concentration-dependent manner in primary isolated platelets, which was blocked by angiotensin II type 1 receptor (AT1R) antagonist losartan, but not by angiotensin II type 2 receptor (AT2R) antagonist PD123319. Moreover, inhibiting AT1R by losartan attenuated LPS-induced platelet apoptosis and alleviated sepsis-associated thrombocytopenia. Furthermore, Ang II treatment induced oxidative stress level in a concentration-dependent manner in primary isolated platelets, which was partially reversed by the AT1R antagonist losartan. The present study demonstrated that elevated Ang II directly stimulated platelet apoptosis through promoting oxidative stress in an AT1R-dependent manner in sepsis-associated thrombocytopenia. The results would helpful for understanding the role of RAS system in sepsis-associated thrombocytopenia.


Assuntos
Angiotensina II/farmacologia , Apoptose , Plaquetas/patologia , Estresse Oxidativo , Receptor Tipo 1 de Angiotensina/metabolismo , Sepse/complicações , Trombocitopenia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/química , Receptor Tipo 1 de Angiotensina/genética , Transdução de Sinais , Trombocitopenia/etiologia , Trombocitopenia/metabolismo
17.
Opt Express ; 29(23): 37418-37428, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808813

RESUMO

In this paper, we propose an optofluidic lenticular lens array (OLLA) for a two-dimensional/three-dimensional (2D/3D) switchable display. The OLLA includes a bottom substrate layer with lenticular lens structure, a microfluidic layer with microchannels, and a top substrate layer with inlets as well as outlets. A micro gap is formed between the lenticular lens of the bottom substrate layer and the top substrate layer. When air is in the micro gap, the OLLA behaves as a lenticular lens array, which can realize 3D display. When fluid is filled in the micro gap, because the refractive index of the fluid is the same with the lenticular lens structure, the OLLA equivalents to a transparent flat panel, which can realize a 2D display. Experiments verify that a switchable 2D/3D display prototype based on this OLLA and a smartphone achieves both high-resolution 2D display and high-quality 3D display.

18.
Opt Express ; 29(23): 37464-37475, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808817

RESUMO

A four-mode 2D/3D switchable display using a 1D/2D convertible liquid crystal (LC) lens array is proposed in this paper. The LC lens array is composed of two orthogonal LC lens arrays, with a λ/2 film in the middle to rotate the polarization by 90°. Based on the LC lens array, a four-mode 2D/3D switchable display is realized, which is switchable between the turn-off and turn-on states: when the operating voltage V1 = 0, V2 = 0, the display operates in mode I, which is 2D display; when the operating voltage V1 = 0, V2 = 0, the display operates in mode II, and the 3D display effect is in x direction; when the operating voltage V1 = 0, V2 = 0, the display operates in mode III, and the 3D display effect is in y direction; when the operating voltage V1 = 0, V2 = 0, the display operates in mode IV, the 3D display effect is in x-y plane. Experimental results indicate that the LC lens array has simple fabrication process, low operating voltage (∼5.4V), and short focal length. Moreover, based on the designed LC lens array, the 2D/3D switchable display shows no moiré pattern.

19.
Opt Lett ; 46(23): 5870-5873, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851911

RESUMO

A fast responsive two-dimensional/three-dimensional (2D/3D) switchable display is demonstrated based on an active liquid crystal (LC) microlens array and a twisted nematic (TN) cell. Compared with the traditional LC microlens array, the fabricated LC microlens array has more ideal phase profile and better focusing effect. The TN cell can switch the polarization direction of the incident light with a very short switching time (4.3 ms) and a small driving voltage (5Vrms). By introducing the tilted elemental image arrays and tilted LC lens array, the moiré patterns are eliminated. The fast switching of the 2D/3D display can be realized by applying or removing voltage to the TN cell. The fast responsive 2D/3D switchable display with the LC microlens array and the TN cell is thin and compact without moiré pattern compared with other 2D/3D switchable display devices.

20.
Crit Care Med ; 47(7): e587-e596, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31205087

RESUMO

OBJECTIVES: The R-spondin family attenuates tissue damage via tightening endothelium and preventing vascular leakage. This study aims to investigate whether R-spondins protect against mechanical stretch-induced endothelial dysfunction and lung injury and to reveal the underlying mechanisms. DESIGN: Randomized controlled study. SETTING: University research laboratory. SUBJECTS: Patients scheduled to undergo surgery with mechanical ventilation support. Adult male Institute of Cancer Research mice. Primary cultured mouse lung vascular endothelial cells. INTERVENTIONS: Patients underwent a surgical procedure with mechanical ventilation support of 3 hours or more. Mice were subjected to mechanical ventilation (6 or 30 mL/kg) for 0.5-4 hours. Another group of mice were intraperitoneally injected with 1 mg/kg lipopolysaccharide, and 12 hours later subjected to mechanical ventilation (10 mL/kg) for 4 hours. Mouse lung vascular endothelial cells were subjected to cyclic stretch for 4 hours. MEASUREMENTS AND MAIN RESULTS: R-spondin1 were downregulated in both surgical patients and experimental animals exposed to mechanical ventilation. Intratracheal instillation of R-spondin1 attenuated, whereas knockdown of pulmonary R-spondin1 exacerbated ventilator-induced lung injury and mechanical stretch-induced lung vascular endothelial cell apoptosis. The antiapoptotic effect of R-spondin1 was mediated through the leucine-rich repeat containing G-protein coupled receptor 5 in cyclic stretched mouse lung vascular endothelial cells. We identified apoptosis-stimulating protein of p53 2 as the intracellular signaling protein interacted with leucine-rich repeat containing G-protein coupled receptor 5. R-spondin1 treatment decreased the interaction of apoptosis-stimulating protein of p53 2 with p53 while increased the binding of apoptosis-stimulating protein of p53 2 to leucine-rich repeat containing G-protein coupled receptor 5, therefore resulting in inactivation of p53-mediated proapoptotic pathway in cyclic stretched mouse lung vascular endothelial cells. CONCLUSIONS: Mechanical ventilation leads to down-regulation of R-spondin1. R-spondin1 may enhance the interaction of leucine-rich repeat containing G-protein coupled receptor 5 and apoptosis-stimulating protein of p53 2, thus inactivating p53-mediated proapoptotic pathway in cyclic stretched mouse lung vascular endothelial cells. R-spondin1 may have clinical benefit in alleviating mechanical ventilator-induced lung injury.


Assuntos
Regulação para Baixo/fisiologia , Pulmão/fisiopatologia , Trombospondinas/sangue , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Animais , Líquido da Lavagem Broncoalveolar/citologia , Células Cultivadas , Modelos Animais de Doenças , Masculino , Camundongos , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
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