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1.
Plant Physiol Biochem ; 210: 108663, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38678947

RESUMO

The vacuolar H+-ATPase (V-ATPase) is a multi-subunit membrane protein complex, which plays pivotal roles in building up an electrochemical H+-gradient across tonoplast, energizing Na+ sequestration into the central vacuole, and enhancing salt stress tolerance in plants. In this study, a B subunit of V-ATPase gene, PbVHA-B1 was discovered and isolated from stress-induced P. betulaefolia combining with RT-PCR method. The RT-qPCR analysis revealed that the expression level of PbVHA-B1 was upregulated by salt, drought, cold, and exogenous ABA treatment. Subcellular localization analyses showed that PbVHA-B1 was located in the cytoplasm and nucleus. Moreover, overexpression of PbVHA-B1 gene noticeably increased the ATPase activity and the tolerance to salt in transgenic Arabidopsis plants. In contrast, knockdown of PbVHA-B1 gene in P.betulaefolia by virus-induced gene silencing had reduced resistance to salt stress. In addition, using yeast one-hybride (Y1H) and yeast two-hybride (Y2H) screens, PbbHLH62, a bHLH transcription factor, was identified as a partner of the PbVHA-B1 promoter and protein. Then, we also found that PbbHLH62 positively regulate the expression of PbVHA-B1 and the ATPase activity after salt stress treatment. These findings provide evidence that PbbHLH62 played a critical role in the salt response. Collectively, our results demonstrate that a PbbHLH62/PbVHA-B1 module plays a positive role in salt tolerance by maintain intracellular ion and ROS homeostasis in pear.


Assuntos
Homeostase , Proteínas de Plantas , Pyrus , Espécies Reativas de Oxigênio , Tolerância ao Sal , Sódio , Tolerância ao Sal/genética , Pyrus/metabolismo , Pyrus/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Espécies Reativas de Oxigênio/metabolismo , Sódio/metabolismo , Plantas Geneticamente Modificadas , Potássio/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , ATPases Vacuolares Próton-Translocadoras/metabolismo , ATPases Vacuolares Próton-Translocadoras/genética , Arabidopsis/genética , Arabidopsis/metabolismo
2.
Plant Sci ; 341: 112009, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316345

RESUMO

NAD+ and NADH play critical roles in energy metabolism, cell death, and gene expression. The NADH-ubiquinone oxidoreductase complex (Complex I) has been long known as a key enzyme in NAD+ and NADH metabolism. In the present study, we found and analyzed a new subunit of Complex I (NDH9), which was isolated from Pyrus ussuriensis combined with RT-PCR. Following infection with A. alternata, RT-qPCR analysis demonstrated an increase in the expression of PuNDH9. Genetic manipulation of PuNDH9 levels suggested that PuNDH9 plays key roles in NADH/NAD+ homeostasis, defense enzyme activities, ROS generation, cell death, gene expression, energy metabolism, and mitochondrial functions during the pear- A. alternata interaction. Furthermore, Y2H, GST-pull down, and a split-luciferase complementation imaging assays revealed that PuNDH9 interacts with PuPR1. We discover that PuNDH9 and PuPR1 synergistically activate defense enzyme activities, ROS accumulation, cell death, and plant defenses. Collectively, our findings reveal that PuNDH9 is likely important for plant defenses.


Assuntos
Complexo I de Transporte de Elétrons , NAD , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , NAD/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Morte Celular
3.
Plant Sci ; 341: 112015, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325662

RESUMO

Flavonoids are plant pigments that play a major role in plant defense and have significant health benefits to humans. Chalcone synthase (CHS) is an important enzyme in flavonoid biosynthesis and investigation transcription factors (TFs) regulating its expression and downstream targets is critical to understanding its mechanism. Here, a novel TF, PbWRKY18, was isolated from the pear Pyrus betulaefolia. Its expression was evaluated in various tissues by RT-PCR, particularly in response to Alternaria alternata, the pathogen responsible for black spot disease, and exogenous hormone administration. The PbWRKY18 protein was primarily found in the nucleus where it regulated transcriptional activity. Yeast one-hybrid and dual-luciferase reporter assays showed a strong association between PbWRKY18 and the PbCHS3 promoter, which drives PbCHS3 expression. It was also found that PbCHS3 was critical for the development of resistance against black spot disease. In addition, PbWRKY18 was found to significantly increase the expression of PbCHS3 and salicylic acid-related genes, as well as defense enzyme activity and tolerance to black spot disease. PbWRKY18 or PbCHS3 knockdown in pear attenuates resistance to Alternaria alternata. In summary, the study identified a novel WRKY18-CHS3 axis involved in resistance against black spot disease in pear.


Assuntos
Aciltransferases , Pyrus , Humanos , Pyrus/genética , Alternaria , Regiões Promotoras Genéticas
4.
Opt Lett ; 48(22): 5992-5995, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966771

RESUMO

A numerical calculating model is proposed for characterizing the BER performance of the detector working among the 2-D asymmetric distorted spot on the effects of atmospheric turbulence under weak turbulent conditions. Based on the isotropy of the beam wander effect, we introduce a beam wander vector to describe the behavior of the detector drifting among the receiving plane. Furthermore, using the cake-cutting method, the overall PDF of the light intensity is approximated by the average PDF of light intensity intercepted by the detector drifting in all different directions. The results demonstrate that the model obtains the overall PDF of the light intensity received by the detector and analyzes the BER performance of the communication system efficiently. Being an extension of the traditional 1-D calculation, our proposed model has important implications for designing the space uplink optical communication system.

5.
Adv Mater ; 35(45): e2305535, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37607503

RESUMO

The progress of solar-driven water-splitting technology has been impeded by the limited light response capability of semiconductor materials. Despite attempts to leverage nearly 50% of infrared radiation for photothermal synergy and catalytic reaction enhancement, heat loss during liquid phase reactions results in low energy conversion efficiency. Here, the photothermally driven catalytic water-splitting system, which designs K-SrTiO3 -loaded TiN silica wool at the water-air interface. Photocatalytic tests and density functional theory calculations demonstrate that the thermal effect transforms liquid water into water vapor, thereby reducing the reaction free energy of catalysts and improving the transmission rate of catalytic products. Hence, the hydrogen evolution rate reaches 275.46 mmol m-2  h-1 , and the solar-to-hydrogen (STH) efficiency is 1.81% under 1 sun irradiation in this gas-solid system, which is more than twice that of liquid water splitting. This novel photothermal catalytic pathway, which involves a coupled reaction of water evaporation and water splitting, is anticipated to broaden the utilization range of the solar spectrum and significantly enhance the conversion efficiency of STH.

6.
J Hematol Oncol ; 16(1): 84, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37501059

RESUMO

Hyperhomocysteinemia (HHcy) is closely associated with thrombotic diseases such as myocardial infarction and stroke. Enhanced platelet activation was observed in animals and humans with HHcy. However, the influence of HHcy on thrombopoiesis remains largely unknown. Here, we reported increased platelet count (PLT) in mice and zebrafish with HHcy. In hypertensive patients (n = 11,189), higher serum level of total Hcy was observed in participants with PLT ≥ 291 × 109/L (full adjusted ß, 0.59; 95% CI 0.14, 1.04). We used single-cell RNA sequencing (scRNA-seq) to characterize the impact of Hcy on transcriptome, cellular heterogeneity, and developmental trajectories of megakaryopoiesis from human umbilical cord blood (hUCB) CD34+ cells. Together with in vitro and in vivo analysis, we demonstrated that Hcy promoted megakaryocytes (MKs) differentiation via growth hormone (GH)-PI3K-Akt axis. Moreover, the effect of Hcy on thrombopoiesis is independent of thrombopoietin (TPO) because administration of Hcy also led to a significant increase of PLT in homozygous TPO receptor (Mpl) mutant mice and zebrafish. Administration of melatonin effectively reversed Hcy-induced thrombopoiesis in mice. ScRNA-seq showed that melatonin abolished Hcy-facilitated MK differentiation and maturation, inhibited the activation of GH-PI3K-Akt signaling. Our work reveals a previously unrecognized role of HHcy in thrombopoiesis and provides new insight into the mechanisms by which HHcy confers an increased thrombotic risk.Trial Registration clinicaltrials.gov Identifier: NCT00794885.


Assuntos
Hiper-Homocisteinemia , Melatonina , Humanos , Camundongos , Animais , Trombopoese/genética , Megacariócitos , Plaquetas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/genética , Peixe-Zebra , Hormônio do Crescimento/farmacologia , Melatonina/farmacologia , Hiper-Homocisteinemia/complicações , Diferenciação Celular
7.
Cell Biol Toxicol ; 39(6): 3077-3100, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37495868

RESUMO

Hyperhomocysteinemia (HHcy) plays a salient role in male infertility. However, whether HHcy interferes with testosterone production remains inconclusive. Here, we reported a lower serum testosterone level in HHcy mice. Single-cell RNA sequencing revealed that genes related to testosterone biosynthesis, together with nuclear receptor subfamily 5 group A member 1 (Nr5a1), a key transcription factor for steroidogenic genes, were downregulated in the Leydig cells (LCs) of HHcy mice. Mechanistically, Hcy lowered trimethylation of histone H3 on lysine 4 (H3K4me3), which was bound on the promoter region of Nr5a1, resulting in downregulation of Nr5a1. Intriguingly, we identified an unknown cell cluster annotated as Macrophage-like Leydig cells (McLCs), expressing both LCs and macrophages markers. In HHcy mice, McLCs were shifted toward pro-inflammatory phenotype and thus promoted inflammatory response in LC. Betaine supplementation rescued the downregulation of NR5A1 and restored the serum testosterone level in HHcy mice. Overall, our study highlights an etiological role of HHcy in LCs dysfunction.


Assuntos
Hiper-Homocisteinemia , Células Intersticiais do Testículo , Camundongos , Masculino , Animais , Células Intersticiais do Testículo/metabolismo , Testosterona , Hiper-Homocisteinemia/metabolismo , Macrófagos/metabolismo , Fatores de Transcrição/genética
8.
J Sci Food Agric ; 103(13): 6553-6565, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37229574

RESUMO

BACKGROUND: Post-harvest quality assurance is a crucial link between grain production and end users. It is essential to ensure that grain does not deteriorate due to heating during storage. To visualize the temperature distribution of a grain pile, the present study proposed a three-dimensional (3D) temperature field visualization method based on an adaptive neighborhood clustering algorithm (ANCA). The ANCA-based visualization method contains four calculation modules. First, discrete grain temperature data, obtained by sensors, are collected and interpolated using back propagation (BP) neural networks to model the temperature field. Then a new adaptive neighborhood clustering algorithm is applied to divide interpolation data into different categories by combining spatial characteristics and spatiotemporal information. Next, the Quickhull algorithm is used to compute the boundary points of each cluster. Finally, the polyhedrons determined by boundary points are rendered into different colors and are constructed in a 3D temperature model of the grain pile. RESULTS: The experimental results show that ANCA is much better than the DBSCAN and MeanShift algorithms on compactness (around 95.7% of tested cases) and separation (approximately 91.3% of tested cases). Moreover, the ANCA-based visualization method for grain pile temperatures has a shorter rendering time and better visual effects. CONCLUSION: This research provides an efficient 3D visualization method that allows managers of grain depots to obtain temperature field information for bulk grain visually in real time to help them protect grain quality during storage. © 2023 Society of Chemical Industry.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Imageamento Tridimensional , Imageamento Tridimensional/métodos , Temperatura , Algoritmos , Análise por Conglomerados , Tecnologia
9.
J Colloid Interface Sci ; 626: 662-673, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35810705

RESUMO

SrTiO3 as a photocatalytic overall water splitting material has received extensive attention in recent years, while effectively suppressing Ti3+ is the key to enhancing the photocatalytic performance. Herein, a polymerizable complexation method is employed to enable Al3+ uniformly enter into SrTiO3 lattice for reducing Ti3+, and substituting Ti4+ with the formation of oxygen vacancy. Thus, the photogenerated carrier transport is promoted, and the resulting appropriate surface oxygen vacancy is also conducive to the adsorption of water molecules and OH*. The optimized 2% Al3+-doped SrTiO3 possesses a lower Ti3+ concentration, compared with the same sample prepared by the solid-phase griding method. Consequently, 2% Al-STO sample deposited co-catalysts achieves the highest activity and durability with the H2 and O2 evolution rates of 1.256 mmol·h-1 and 0.692 mmol·h-1 (0.04 g catalyst), respectively, corresponding to the AQE value of 55.46% at 365 nm. The characterizations and DFT calculation results reveal that the uniform Al3+ doping promotes the increase in the surface oxygen vacancy, which is beneficial for accelerating the reduction reaction and facilitating carrier separation and migration, therefore enhancing the overall water splitting reaction.

10.
Materials (Basel) ; 15(12)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35744293

RESUMO

In this study, ball mill pretreated iron ore tailings were modified with tetraethoxysilane (TEOS) and hexadecyltrimethoxysilane (HDTMS) to obtain iron ore tailings/polysiloxane (IOT/POS) superhydrophobic powders, which were subsequently mixed with chloroprene rubber solution (CRS) to prepare durable superhydrophobic composite coatings. The effect of HDTMS amount and reaction time on the wettability of the superhydrophobic powder was investigated. The influence of the superhydrophobic powders concentration on the wettability of the composite coatings as well as the degree of damage of the superhydrophobicity of the composite coating was analyzed by using the sandpaper abrasion and tape peeling tests. Further, SEM and FTIR were used to analyze the formation mechanism of the IOT/POS superhydrophobic powders and coatings. The results showed for an HDTMS amount of 2.5 mmol and reaction time of 4 h, the contact angle of the IOT/POS powder was 157.3 ± 0.6°, whereas the slide angle was determined to be 5.9 ± 0.8°. For an IOT/POS powder content of 0.06 g/mL in CRS, the contact angle value of the superhydrophobic composite coating was 159.2 ± 0.5°, whereas the slide angle value was 5.5 ± 0.8°. The superhydrophobic composite coating still maintained the superhydrophobicity after the sandpaper abrasion and tape peeling tests, which indicated the iron ore tailings solid waste has the potential to prepare superhydrophobic coatings.

11.
Chem Commun (Camb) ; 58(58): 8101-8104, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35766812

RESUMO

Appropriate metal ions can act as transport media for enhancing the water oxidation of a BiVO4 photoanode by balancing the hole transfer and consumption in a reaction.

12.
Materials (Basel) ; 15(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35268987

RESUMO

In order to realize the high value-added resource utilization of solid waste and reduce the cost of rubber manufacturing, iron ore tailings (IOTs) were used as raw material to prepare a reinforcing filler of rubber through ultrafine grinding and surface organic modification techniques. We studied the effects of ball mill grinding conditions on the particle size and distribution of grinded iron ore tailings (G-IOTs). The effects of bis-(triethoxy-silyl-propyl)-tetrasulfide (Si69)-modified G-IOT (Si69-G-IOT) loading levels on the cure characteristics, static mechanical and dynamic mechanical properties of the styrene butadiene rubber (SBR) composites were also explored in this paper. The grinding and modification mechanism of IOTs and the combination of filler and SBR matrix were explored by grinding simulation of population balance model, X-ray diffraction analysis, Fourier transform infrared spectroscopy and scanning electron microscopy. The results showed that when grinding IOTs at 2000 r/min for 150 min, the particle size distribution of the resulting G-IOTs was the narrowest, with a D90 value of 4.42 µm. The tensile strength and elongation at break of SBR filled with 120 phr Si69-G-IOT were 14.97 MPa and 596.36%, respectively.

13.
BMC Musculoskelet Disord ; 22(1): 383, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33894744

RESUMO

BACKGROUND: Symptomatic pulmonary embolism (PE) after knee arthroscopy is extremely rare. If the embolism is not treated promptly, the patient may die. Bilateral pulmonary embolism with associated pulmonary infarct without concomitant deep vein thrombosis has never been reported following routine knee arthroscopy. CASE PRESENTATION: A 50-year-old female patient with no other risk factors other than hypertension, obesity, varicose veins in the ipsilateral lower extremities and elevated triglyceride (TG) presented to our ward. She had experienced sudden chest tightness, polypnea and fainting after going to the bathroom the morning of the second postoperative day and received emergency medical attention. Colour ultrasonography of the extremities showed no deep vein thrombosis. Lung computed tomography angiography (CTA) showed multiple embolisms scattered in both pulmonary artery branches. Thus, emergency interventional thrombolysis therapy was performed, followed by postoperative symptomatic treatment with drugs with thrombolytic, anticoagulant and protective activities. One week later, lung CTA showed a significant improvement in the PEs compared with those in the previous examination. Since the aetiology of PE and no obvious symptoms were discerned, the patient was discharged. CONCLUSION: Although knee arthroscopy is a minimally invasive and quick procedure, the risk factors for PE in the perioperative period should be considered and fully evaluated to enhance PE detection. Moreover, a timely diagnosis and effective treatment are important measures to prevent and cure PE after knee arthroscopy. Finally, clear guidelines regarding VTE thromboprophylaxis following knee arthroscopy in patients with a low risk of VTE development are needed.


Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Anticoagulantes , Artroscopia/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/etiologia , Fatores de Risco , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
14.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(7): 854-859, 2019 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-31298003

RESUMO

OBJECTIVE: To compare the early effectiveness and safety of simultaneous bilateral and staged bilateral unicompartmental knee arthroplasty (UKA) in treatment of anteromedial compartment osteoarthritis. METHODS: The clinical data of 31 patients with bilateral anteromedial compartment osteoarthritis who underwent bilateral UKAs between January 2015 and January 2017 was retrospectively analyzed. Of them, 17 patients were treated with simultaneous bilateral UKAs (simultaneous group) and 14 patients with staged bilateral UKAs (staged group). There was no significant difference in gender, age, body mass index, osteoarthritis grading, and preoperative hip-knee-ankle angle, knee society score (KSS), visual analogue scale (VAS) score, and range of motion (ROM) of knee between the two groups ( P>0.05). The operation time, blood loss, hospitalization stay, minimum hemoglobin value during 10 days after operation, and hospitalization cost were recorded. The staged group was compared by the sum of two operations. The effectiveness was evaluated by KSS score, VAS score, ROM at 3, 6, 12 months after operation, and patient satisfaction scores were recorded at 12 months after operation. RESULTS: The operation time, hospitalization stay, and hospitalization cost of the simultaneous group were significantly lower than those of the staged group ( P<0.05). There was no significant difference in blood loss and the minimum hemoglobin value during 10 days after operation between the two groups ( P>0.05). Superficial infection occurred in 1 side of 1 case (7.1%) in staged group. Postoperative delirium occurred in 1 case (5.9%) in simultaneous group. There was no significant difference in incidence of postoperative complications between the two groups ( P=1.000). Patients in both groups were followed up 12-32 months (mean, 24.7 months). There was no significant difference in KSS score between the two groups at 3 months after operation ( t=0.896, P=0.392). KSS scores were significanly higher in simultaneous group than in staged group at 6 and 12 months after operation ( P<0.05). There was no significant difference in ROM and VAS scores between the two groups at 3, 6, and 12 months after operation ( P>0.05). At 12 months after operation, the patient satisfaction scores were significantly higher in simultaneous group than in staged group ( P<0.05). X-ray films showed no loosening of the prosthesis in the two groups. CONCLUSION: Simultaneous bilateral UKAs has the same security as staged bilateral UKAs. Meanwhile knee function recovery was better, hospitalization stay and hospitalization cost reduced, and patient satisfaction was higher in simultaneous bilateral UKAs.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
16.
Antioxid Redox Signal ; 30(15): 1797-1816, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-29890853

RESUMO

AIMS: Mitochondrial fragmentation is a crucial mechanism contributing to tubular cell apoptosis during acute kidney injury (AKI). However, the mechanism of modulating mitochondrial dynamics during AKI remains unclear. Numb is a multifunction adaptor protein that is expressed in renal tubules. The aim of the present study was to evaluate the role of Numb in mitochondrial dysfunction during AKI. RESULTS: The expression of Numb was upregulated in both ischemia-reperfusion- and cisplatin-induced AKI. Depletion of Numb from proximal tubules (PT-Nb-KO) exacerbated AKI shown as more severe renal tubular damage and higher serum creatinine than wild-type mice. Numb depletion alone significantly increased mitochondrial fragmentation without altering mitochondrial mass and function, including adenosine triphosphate production, mitochondrial membrane potential, oxygen consumption, and reactive oxygen species production. However, mitochondrial fragmentation and dysfunction were significantly aggravated after cisplatin exposure in PT-Nb-KO mice. Mechanistically, Numb depletion triggered dynamin-related protein 1 (Drp1) recruitment to mitochondria by increasing the phosphorylation of Drp1 at serine 656 residue (human Drp1 ser637). Inhibiting the activity of Rho-associated coiled-coil containing protein kinase (ROCK) by Y-27632 attenuated phosphorylation of Drp1 ser656 and mitochondrial fragmentation in Numb-deficient cells. Administration of mdivi-1, a pharmacological inhibitor of Drp1, restored mitochondrial morphology, attenuated cisplatin-induced tubular injury, and renal dysfunction in PT-Nb-KO mice. Innovation and Conclusion: Our data suggest that Numb depletion promotes mitochondrial fragmentation by promoting the phosphorylation of Drp1 Ser637 and thus exacerbates cisplatin-induced mitochondrial dysfunction and tubular cell apoptosis. These findings add a novel insight into modulating mechanism of mitochondrial dynamics during AKI.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Proteínas Quinases Associadas com Morte Celular/genética , Suscetibilidade a Doenças , Proteínas de Membrana/metabolismo , Dinâmica Mitocondrial/genética , Proteínas do Tecido Nervoso/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose , Biomarcadores , Biópsia , Cisplatino/efeitos adversos , Proteínas Quinases Associadas com Morte Celular/metabolismo , Progressão da Doença , Técnicas de Silenciamento de Genes , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Proteínas de Membrana/genética , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas do Tecido Nervoso/genética , Transporte Proteico , Radiação Ionizante , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
17.
Neural Regen Res ; 12(8): 1329-1337, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28966649

RESUMO

Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 µg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 µg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.

18.
Comput Math Methods Med ; 2015: 185726, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25945120

RESUMO

The key problem of computer-aided diagnosis (CAD) of lung cancer is to segment pathologically changed tissues fast and accurately. As pulmonary nodules are potential manifestation of lung cancer, we propose a fast and self-adaptive pulmonary nodules segmentation method based on a combination of FCM clustering and classification learning. The enhanced spatial function considers contributions to fuzzy membership from both the grayscale similarity between central pixels and single neighboring pixels and the spatial similarity between central pixels and neighborhood and improves effectively the convergence rate and self-adaptivity of the algorithm. Experimental results show that the proposed method can achieve more accurate segmentation of vascular adhesion, pleural adhesion, and ground glass opacity (GGO) pulmonary nodules than other typical algorithms.


Assuntos
Diagnóstico por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico , Algoritmos , Análise por Conglomerados , Bases de Dados Factuais , Detecção Precoce de Câncer/métodos , Lógica Fuzzy , Humanos , Processamento de Imagem Assistida por Computador/métodos , Pulmão/irrigação sanguínea , Modelos Estatísticos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X
19.
J Renin Angiotensin Aldosterone Syst ; 16(4): 995-1000, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25501308

RESUMO

BACKGROUND: The authors tested the hypothesis that combined use of dexmedetomidine on fetal rats during isoflurane exposure in maternal anesthesia can attenuate the abnormal spatial learning and memory abilities in adults via the renin-angiotensin-aldosterone system. METHODS: Fifty timed-pregnancy rats were randomly assigned to five groups (Dex+Iso, Sal+Iso, Sal+Oxy, Dex+Oxy, and a control group ) on embryonic day 14 to receive five different dispositions, i.e. combined injection of dexmedetomidine (Dex) or saline (Sal) and inhalation of isoflurane (Iso), oxygen (Oxy), or normal air for 4 h (n = 10). RESULTS: The latency time(s) from day 1 to day 4 all showed a decreasing tendency in all four groups. The synaptic count of the Sal+Iso group was significantly lower than the Control group (p < 0.05), suggesting that severe neurodegeneration occurred under the influence of fetal isoflurane exposure. In contrast, the synapse count of the Dex+Iso group was near to that of Control group. The rats are protected in neurodevelopmental, normal development. CONCLUSION: Combine use of dexmedetomidine during exposure to isoflurane in utero during middle-pregnancy can attenuate the impairment of spatial learning and memory abilities for the rats in adulthood.


Assuntos
Dexmedetomidina/farmacologia , Memória/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Animais , Feminino , Período de Latência Psicossexual , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos
20.
Curr Comput Aided Drug Des ; 10(3): 217-25, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25756667

RESUMO

Antibody drugs are used in the treatment of many chronic diseases. Recently, however, patients and doctors have encountered problems with drug resistance, and improving the affinity of antibody drugs has therefore become a pressing issue. Ibalizumab is a humanized monoclonal antibody that binds human CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1). In this study, we sought to identify the key residues of the complementaritydetermining regions (CDRs) of ibalizumab. Virtual alanine mutations (complementarity-determining regions of ibalizumab) were also studied using solvated interaction energies derived from molecular dynamics and the explicit water model. Using 1,000 nanosecond molecular dynamic simulations, we identified six residues: Tyr50 [HCDR2], Tyr53 [HCDR3], Asp58 [HCDR2], Glu95 [HCDR2], and Arg95 [LCDR3]. The Robetta alanine-scanning mutagenesis method and crystallographic information were used to verify our simulations. Our simulated binding affinity of -17.33 kcal/mol is close to the experimentally determined value of -16.48 kcal/mol. Our findings may be useful for protein engineering the structure of the ibalizumab-human CD4 receptor complex. Moreover, the six residues that we identified may play a significant role in the development of bioactive antibody analogues.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD4/imunologia , Inibidores da Fusão de HIV/imunologia , Simulação de Dinâmica Molecular , Alanina/genética , Anticorpos Monoclonais/metabolismo , Antígenos CD4/metabolismo , Cristalografia por Raios X , Inibidores da Fusão de HIV/metabolismo , Humanos , Mutagênese
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