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Photocatalytic ozonation is considered to be a promising approach for the treatment of refractory organic pollutants, but the design of efficient catalyst remains a challenge. Surface modification provides a potential strategy to improve the activity of photocatalytic ozonation. In this work, density functional theory (DFT) calculations were first performed to check the interaction between O3 and TiO2-OH (surface hydroxylated TiO2) or TiO2-F (surface fluorinated TiO2), and the results suggest that TiO2-OH displays better O3 adsorption and activation than does TiO2-F, which is confirmed by experimental results. The surface hydroxyl groups greatly promote the O3 activation, which is beneficial for the generation of reactive oxygen species (ROS). Importantly, TiO2-OH displays better performance towards pollutants (such as berberine hydrochloride) removal than does TiO2-F and most reported ozonation photocatalysts. The total organic carbon (TOC) removal efficiency reaches 84.4% within two hours. This work highlights the effect of surface hydroxylation on photocatalytic ozonation and provides ideas for the design of efficient photocatalytic ozonation catalysts.
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Recently, amorphous materials have gained great attention as an emerging kind of functional material, and their characteristics such as isotropy, absence of grain boundaries, and abundant defects are very likely to outrun the disadvantages of crystalline counterparts, such as low conductivity, and ultimately lead to improved charge transfer efficiency. Herein, we investigated the effect of amorphization on the charge transfer process and photocatalytic performance with a phosphonate-based metal-organic framework (FePPA) as the research object. Comprehensive experimental results suggest that compared to crystalline FePPA, amorphous FePPA has more distorted metal nodes, which affects the electron distribution and consequently improves the photogenerated charge separation efficiency. Meanwhile, the distorted metal nodes in amorphous FePPA also greatly promote the adsorption and activation of O2. Hence, amorphous FePPA exhibits a better performance of photocatalytic C(sp3)-H bond activation for selective oxidation of toluene to benzaldehyde. This work illustrates the advantages of amorphous MOFs in the charge transfer process, which is conducive to the further development of high performance MOFs-based photocatalysts.
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BACKGROUND: Postoperative sleep disturbance (PSD) is a prevalent clinical complication that may arise due to various factors. The purpose of this investigation is to identify the risk factors for PSD in spinal surgery and establish a risk prediction nomogram. METHODS: The clinical records of individuals who underwent spinal surgery from January 2020 to January 2021 were gathered prospectively. The least absolute shrinkage and selection operator (LASSO) regression, along with multivariate logistic regression analysis, was employed to establish independent risk factors. A nomogram prediction model was devised based on these factors. The nomogram's effectiveness was evaluated and verified via the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). RESULTS: A total of 640 patients who underwent spinal surgery were analyzed in this investigation, among which 393 patients experienced PSD with an incidence rate of 61.4%. After conducting LASSO regression and logistic regression analyses using R software on the variables in training set, 8 independent risk factors associated to PSD were identified, including female, preoperative sleep disorder, high preoperative anxiety score, high intraoperative bleeding volume, high postoperative pain score, dissatisfaction with ward sleep environment, non-use of dexmedetomidine and non-use of erector spinae plane block (ESPB). The nomogram and online dynamic nomogram were constructed after incorporating these variables. In the training and validation sets, the area under the curve (AUC) in the receiver operating characteristic (ROC) curves were 0.806 (0.768-0.844) and 0.755 (0.667-0.844), respectively. The calibration plots indicated that the mean absolute error (MAE) values in both sets were respectively 1.2% and 1.7%. The decision curve analysis demonstrated the model had a substantial net benefit within the range of threshold probabilities between 20% and 90%. CONCLUSIONS: The nomogram model proposed in this study included eight frequently observed clinical factors and exhibited favorable accuracy and calibration. TRIAL REGISTRATION: The study was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2200061257, 18/06/2022).
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Nomogramas , Transtornos do Sono-Vigília , Adulto , Feminino , Humanos , Povo Asiático , Procedimentos Neurocirúrgicos , Estudos ProspectivosRESUMO
OBJECTIVE: The contractile behavior of collecting lymphatic vessels occurs in essential hypertension in response to homeostasis, suggesting a possible role for microcirculation. We aimed to clarify the nature of the lymphatic microcirculation profile in spontaneously hypertensive rats (SHRs) and normotensive controls. METHODS: The vasomotion of collecting lymphatic vessels in eight- and thirteen-week-old SHRs and age-matched Wistar-Kyoto rats (WKYs, n = 4 per group) was visualized by intravital video and VasTrack. The lymphatic vasomotion profile (frequency and amplitude) and contractile parameters (contraction fraction and total contractility activity index) were compared. Plasma nitrite/nitrate levels were assessed by the Griess reaction, and plasma endothelin-1 was measured by enzyme-linked immunosorbent assay. RESULTS: WKYs and SHRs differed in the vasomotion of collecting lymphatic vessels. Both eight- and thirteen-week-old WKYs revealed a high-amplitude pumping pattern, whereas a low-amplitude pattern was observed in SHRs. Moreover, compared with age-matched WKYs, SHRs exhibited deteriorated output and reflux capability and lost the ability to regulate collecting lymphatic vasomotion. Additionally, the chemistry complements the microcirculatory lymphatic profile as demonstrated by an increase in plasma nitrite, nitrate, and endothelin-1 in SHRs. ET-1 inhibitor meliorated the lymphatic contractile capability in SHRs partially through regulating frequency of lymphatic vasomotion. CONCLUSIONS: We used an intravital lymphatic imaging system to observe that SHRs exhibit an impaired collecting lymphatic vasomotion profile and deteriorated contractility and reflux.
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Hipertensão , Vasos Linfáticos , Ratos , Animais , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Microcirculação , Endotelina-1 , Nitratos , Nitritos , Pressão SanguíneaRESUMO
We experimentally demonstrate the real-time 100/200/400 Gb/s/λ coherent passive optical networks (PONs) based on silicon photonic integrated transceiver. We investigate different configuration schemes of coherent PONs including: (1) using a Erbium doped optical fiber amplifier (EDFA) as a booster at the transmitter side; (2) using a semiconductor optical amplifier (SOA) as a booster at the transmitter side; (3) using EDFA at the transmitter side and a pre-amplified SOA at receiver side; (4) using an SOA at the transmitter side and an SOA at the receiver side. The performance of these schemes for different data rates of downstream transmission is evaluated, and the appropriate choices under different circumstances are analyzed. The real-time experimental results indicate that the EDFA can be replaced by SOA as a booster at the transmitter side in 100/200 Gb/s/λ coherent PON based on the dual-polarization QPSK (DP-QPSK) scheme with a small performance penalty. In dual-polarization a 16 quadrature amplitude modulation (DP-16QAM) 400â G/s/λ PON system, EDFA booster is preferred because an SOA introduces more nonlinearity for the 16QAM scheme. The power budget of 32.5â dB is achieved for 400 Gb/s/λ coherent PON after the 20â km standard single mode fiber (SSMF) transmission under the soft-decision feedforward error correction (SD-FEC) threshold.
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We sought to propose an innovative vessel blood flow tracking (VBFT) method to extract coronary artery tree (CAT) and to assess the effectiveness of this VBFT versus the single-frame method. Construction of a CAT from a segmented artery is the basis of artificial intelligence-aided angiographic diagnosis. However, construction of a CAT using a single frame remains challenging, due to bifurcations and overlaps in two-dimensional angiograms. Overall, 13,222 angiograms, including 28,539 vessels, were retrospectively collected from 3275 patients and were then annotated. Coronary arteries were automatically segmented by a previously established deep neural networks (DNNs), and the skeleton lines were then extracted from segmentation images to construct CAT using the single-frame method and the VBFT method. Additionally, 1322 angiograms with 2201 vessels were used to test these two methods. Compared to the single-frame method, the VBFT method can significantly improve the accuracy of CAT as (84.3% vs. 72.3%; p < 0.001). Overlap (OV) was higher in the VBFT group than that in the Single-Frame group (91.1% vs. 87.5%; p < 0.001). The VBFT method significantly reduced the incidence of the lack of branching (7.30% vs. 13.9%, p < 0.001), insufficient length (6.70% vs. 11.0%, p < 0.001), and redundant branches (1.60% vs. 3.10%, p < 0.001). The VBFT method improved the extraction of a CAT structure, which will facilitate the development of artificial intelligence-aided angiographic diagnosis. Cardiologists can efficiently diagnose CAD using this method.
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Inteligência Artificial , Vasos Coronários , Algoritmos , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In this work, a Bi-based metal-organic framework (MOF; Bi-MMTAA) with 2-mercapto-4-methyl-5-thiazoleacetic acid (MMTAA) as the organic ligand is synthesized. The crystal structure of Bi-MMTAA was determined by single-crystal X-ray diffraction. Theoretical calculations reveal that Bi-MMTAA is a p-type semiconductor, and electrons can delocalize through the π-conjugation when excited by a photon with an energy higher than the Bi-MMTAA band gap, which is beneficial to charge separation and transfer. The photoelectrical properties suggest that free electrons can be produced over Bi-MMTAA under light irradiation. The photocatalytic results suggest that Bi-MMTAA can decolorize rhodamine B (RhB) and oxidize phenylboronic acid to phenol under visible light (λ > 420 nm), with superoxide radicals being the main reactive oxygen species. Our results enrich the family of Bi-based MOFs and may inspire further exploration of Bi-based MOFs, including both synthesis and potential applications.
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This publication has been retracted by the Editor due to concerns regarding the originality of the figure images. Reference: Xin Wang, Rong Zhao, Honggang Zhang, Min Zhou, Ming Zhang, Tong Qiao. Levo-Tetrahydropalmatine Attenuates Progression of Abdominal Aortic Aneurysm in an Elastase Perfusion Rat Model via Suppression of Matrix Metalloproteinase and Monocyte Chemotactic Protein-1. Med Sci Monit, 2018; 24: 625-660. DOI: 10.12659/MSM.906153.
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Cis-alkenes are ubiquitous in biological molecules, which makes it greatly significant to develop efficient methods toward construction of cis-olefins. Herein, we reported a facile semi-hydrogenation of alkynes to cis-alkenes in an efficient way with cuprous bromide/tributylphosphine as the catalyst and bis(pinacolato)diboron/methanol as the hydrogen donor. The method features convenient and facile reaction conditions, wide substrate scope, high yields, and high stereoselectivity.
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Alcinos , Cobre , Alcinos/química , Cobre/química , Hidrogenação , Alcenos/química , CatáliseRESUMO
OBJECTIVE: As an integrated system, pancreatic microcirculatory disturbance plays a vital role in the pathogenesis of type 1 diabetes mellitus (T1DM), which involves changes in microcirculatory oxygen and microhemodynamics. Therefore, we aimed to release type 1 diabetic and insulin-administrated microcirculatory profiles of the pancreas. METHODS: BALB/c mice were assigned to control, T1DM, and insulin-administrated groups randomly. T1DM was induced by intraperitoneal injection of streptozotocin (STZ). 1.5 IU insulin was administrated subcutaneously to keep the blood glucose within the normal range. After anesthetizing by isoflurane, the raw data set of pancreatic microcirculation was collected by the multimodal device- and computer algorithm-based microcirculatory evaluating system. After adjusting outliers and normalization, pancreatic microcirculatory oxygen and microhemodynamic data sets were imported into the three-dimensional module and compared. RESULTS: Microcirculatory profiles of the pancreas in T1DM exhibited a loss of microhemodynamic coherence (significantly decreased microvascular blood perfusion) accompanied by an impaired oxygen balance (significantly decreased PO2 , SO2 , and rHb). More importantly, with insulin administration, the pathological microcirculatory profiles were partially restored. Meanwhile, there were correlations between pancreatic microcirculatory blood perfusion and PO2 levels. CONCLUSIONS: Our findings establish the first integrated three-dimensional pancreatic microcirculatory profiles of STZ-induced and insulin-administrated T1DM.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Microcirculação , Animais , Diabetes Mellitus Tipo 1/induzido quimicamente , Insulina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Oxigênio , Pâncreas , EstreptozocinaRESUMO
Pericytes facilitate vessel maturation and endothelial barrier functions closely related with the pathogenesis of organ damage from cardiovascular and cerebrovascular diseases such as hypertension. We used a computational-based strategy to first screen for differentially expressed genes and lncRNAs and characterized associations between lncRNAs of microvascular pericytes and hypertension. In total, 22 lncRNAs were upregulated and 46 were downregulated in the rats afflicted with spontaneous hypertension. Expression profiles for lncRNAs were significantly altered in the hypertension afflicted tissue samples and the transcripts have good potential for use as molecular targets to inhibit the progression of hypertension.
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Hipertensão , RNA Longo não Codificante , Animais , Hipertensão/genética , Pericitos/metabolismo , RNA Longo não Codificante/genética , RatosRESUMO
BACKGROUND The aim of this study was to compare the clinical efficacy and postoperative recovery between uterine artery embolization (UAE) and infrarenal aortic balloon occlusion (IABO) in planned cesarean sections for placenta accreta spectrum disorders. MATERIAL AND METHODS A retrospective analysis using the clinical data of 62 patients with placenta previa combined with placenta accreta for planned cesarean between January 2014 and December 2019 was performed at the First People's Hospital in Lianyungang. Thirty-five cases undergoing UAE during cesarean section were defined as group A, while the other 27 cases undergoing IABO were defined as group B. Intraoperative and postoperative parameters including intraoperative blood loss, blood transfusion volume, radiation duration, radiation dose, hysterectomy rate, operation duration, Intensive Care Unit hospitalization, complications, and neonatal outcomes as well as the maternal recovery during follow-up were compared between the 2 groups. RESULTS Intraoperative blood loss, transfusion volume, radiation time, radiation dose, hysterectomy rate, duration of surgery, Intensive Care Unit admission, and complications were higher in group A than group B, with differences being statistically significant (P<0.05). There were no significant differences in birth weight, 1-min Apgar score, neonatal asphyxia rate, admission to Neonatal Intensive Care Unit, breastfeeding time, duration of postpartum lochia, and data related to menstruation between the 2 groups (P>0.05). CONCLUSIONS IABO, which was more effective than UAE in cesarean section of patients with placenta accreta spectrum, could be further applied in treatment.
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Oclusão com Balão/métodos , Cesárea , Placenta Acreta/terapia , Complicações Pós-Operatórias/prevenção & controle , Embolização da Artéria Uterina/métodos , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Histerectomia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Evapotranspiration (ET) is a central process in the climate system that plays a crucial role in the regional water cycle and climate regulation. However, estimating the effects of regional ET on the regional water cycle and climate regulation remains challenging due to the lack of quantitative methods and large-scale direct observational data. This study develops a new method to estimate evapotranspiration at regional scales using long-term monitoring data and the bootstrap resampling approach to calculate the ET unit area per year for China. This study applies the deviance information criterion as a goodness-of-fit index to select the most optimal formula for estimating regional ET for different climatic zones in China. The bootstrap resampling method was used to estimate parameter distribution in different climatic zones based on the outcome of 2000 trials. The results show that the predicted ET of adjacent climates overlaps with each other. The subtropical monsoonal climatic zone had the widest range of predicted ET (0-8000 mm/year), followed by the temperate and monsoonal climatic zones (0-1500 mm/year), mountain plateau climatic zone (0-1000 mm/year), and temperate continental climatic zone (0-500 mm/year). The probability distributions and isopleths of regionally predicted ET were also determined for China. The methods used in this study provide a promising tool to assess the effects of introducing large-scale forestation or restoration of trees on local water resources management.
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Clima , Água , ChinaRESUMO
OBJECTIVE: This study is to explore the exact roles of extracellular vesicle (EVs) miRNAs from brain microvascular pericytes in the pathogenesis of hypertension. RESULTS: Forty-eight significantly differentially expressed miRNAs were identified, of which 17 were found to be upregulated and 31 were found to be downregulated in brain microvascular pericytes of spontaneous hypertensive rats, compared with that of normotension Wistar Kyoto rats. The GO enrichment analysis verified that the target genes were enriched in signaling pathways and molecular functions, such as metal ion binding, nucleotide binding and ATP binding. The KEGG analysis indicated that the target genes were enriched in Linoleic acid, alpha-linolenic acid and sphingolipid metabolism pathways. CONCLUSIONS: Several EV derived miRNAs, such as miR-21-5p, let-7c-5p and let-7a-5p, were found to be abnormally expressed in brain microvascular pericytes obtained from spontaneous hypertensive rats, compared with that of normotension Wistar Kyoto rats. The results of our research provide more insights into the functional link between brain microvascular pericytes and the pathogenesis of hypertension.
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Encéfalo , MicroRNA Circulante/biossíntese , Vesículas Extracelulares/metabolismo , Regulação da Expressão Gênica , Hipertensão/metabolismo , Microvasos/metabolismo , Pericitos/metabolismo , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Vesículas Extracelulares/patologia , Hipertensão/patologia , Microvasos/patologia , Pericitos/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
OBJECTIVES: In cardiovascular disease, deep vein thrombosis is one of the vital symptoms causing pulmonary thromboembolism. However, the pathogenesis of deep vein thrombosis is still not clear. One of the critical factors leading to deep vein thrombosis is the platelet aggregation that is mediated by a set of key genes including platelet membrane protein coded by platelet glycoprotein Ib alpha chain (GPIBA). METHODS: Deep vein thrombosis model was established according to the previous protocol, and venous blood and thrombi were collected for further analysis. RESULTS: The dynamic changes of GPIBA and coagulation factor, von Willebrand factor, were observed in deep vein thrombosis models. Meanwhile, critical proteins participating in adhesion and binding of platelets such as epithelial membrane protein 2 (EMP2), vascular cell adhesion protein 1 (VCAM1), immunoreceptor tyrosine-based activation motif 1 (ITAM1), integrin subunit alpha M (ITGAM), or fibronectin were also differentially expressed in deep vein thrombosis models. CONCLUSIONS: Application of heparin could reverse these dynamic changes in deep vein thrombosis models. Thus, we explained the potential synergic role of GPIBA and von Willebrand factor in regulating the occurrence of deep vein thrombosis and provide therapeutic target against cardiovascular disease.
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Coagulação Sanguínea , Plaquetas/metabolismo , Agregação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Trombose Venosa/metabolismo , Fator de von Willebrand/metabolismo , Animais , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Fibrinolíticos/farmacologia , Fibronectinas/metabolismo , Heparina/farmacologia , Motivo de Ativação do Imunorreceptor Baseado em Tirosina , Glicoproteínas de Membrana/metabolismo , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Transdução de Sinais , Molécula 1 de Adesão de Célula Vascular/metabolismo , Trombose Venosa/sangue , Trombose Venosa/prevenção & controleRESUMO
It has been previously reported that the blockade of interleukin-7 receptor (IL-7R) promotes functional recovery following spinal cord injury (SCI), however, the direct function and molecular mechanism of IL-7 involved in this pathogenic process are unclear. Here, we report that, contrary to IL-7R blockade, the intraspinal administration of IL-7 limits functional recovery following SCI. In addition, IL-7 treatment promotes neuronal apoptosis in spinal cord lesions, which may be attributed to exacerbated focal inflammatory response, as shown by increased accumulation of activated microglia/macrophage and production of proinflammatory mediators. Moreover, IL-7 treatment activates JAK/STAT5 pathway following SCI. At last, more importantly, the pharmacological inhibition of STAT5 abrogates the effects of IL-7 treatment on functional recovery, neuronal apoptosis and focal inflammatory response, suggesting that the effects of IL-7 treatment following SCI are dependent on activating the JAK/STAT5 pathway. Overall, this study reveals the JAK/STAT5 pathway-dependent detrimental role of IL-7 following SCI, and also implies that targeting the IL-7/JAK/STAT5 axis may represent a potential therapeutic approach for SCI treatment.
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Apoptose , Interleucina-7/administração & dosagem , Janus Quinases/metabolismo , Recuperação de Função Fisiológica , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Inflamação/patologia , Injeções Espinhais , Interleucina-7/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Pimozida/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the effects of TNF-α-induced exosomes release on the biological behavior, metabolism, and bioenergetics of HUVECs. METHODS: Exosomes were isolated from conditioned media of HUVECs by ultracentrifugation after treatment with or without TNF-α. HUVECs were treated with or without TNF-α, or different concentrations of exosomes isolated from conditioned media with or without TNF-α induction (TExo and CExo , respectively). RESULTS: The results showed that TNF-α significantly inhibited migration, tube formation, and increased apoptosis rate of HUVECs compared with controls. Furthermore, TNF-α-induced exosomes (TExo ) rather than CExo , indicated similar effects to inhibit migration, tube formation and promote endothelial apoptosis. Although TNF-α treatment did not show a statistical difference, TExo significantly inhibited extracellular OCR compared with controls. TExo could significantly inhibited intracellular OCR in a hypoxia condition. TNF-α significantly increased L-ECA compared with control cells, and TExo showed similar stimulative effect on L-ECA. CONCLUSIONS: TNF-α-induced exosomes could significantly (a) change migration, tube formation, and apoptosis; (b) inhibit endothelial extracellular OCR and intracellular OCR (hypoxia); (c) increase glycolysis rate of the endothelial cells. These data provide new evidence for exploring endothelial behavior regulation using exosomes and their effects on endothelial metabolism and bioenergetics.
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Exossomos/fisiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Apoptose , Movimento Celular , Células Cultivadas , Metabolismo Energético , Exossomos/efeitos dos fármacos , Glicólise , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Células Endoteliais da Veia Umbilical Humana/ultraestrutura , Humanos , Hipóxia , Ácido Láctico/metabolismo , Consumo de OxigênioRESUMO
This work was aimed to study skin blood perfusion, vasomotion and vascular responses of the Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in different stages of age using spectral. Laser-Doppler flowmetry (LDF) was used to examine the ears and limbs of WKY (12 and 48 weeks old) and SHR (12 and 48 weeks old). The skin blood flow oscillations (SBFOs) were studied by wavelet spectral analysis of LDF tracings. Then, we observed that old groups showed decreased perfusion and SBFO in the ears of both SHR and WKY. The SHR showed obviously lower postocclusive reactive hypera (PORH) ratio at the same age. A decreased peak-time occurred in the SHR of old age group. After PORH test, a statistically significant increase was observed within all subintervals in the absolute amplitude of 12-week WKY and only within IV and III subintervals in the absolute amplitude of 12-week SHR. But, the absolute amplitude of 48-week WKY and SHR showed no statistically significant increase within all subintervals. Results indicated that local regulating function of peripheral vascular was impaired in rat with hypertension and aging. Abbreviations LDF: Laser-Doppler flowmetry; SBF: Skin blood flow; SBFO: Skin blood flow oscillation; PORH: Postocclusive reactive hyperemia; SHR: Spontaneously hypertensive rats; WKY: Wistar-Kyoto rats; LDF: Laser-Doppler flowmetry; LDI: Laser Doppler Imaging; BP: Blood pressure.
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Envelhecimento/fisiologia , Hipertensão/fisiopatologia , Microvasos/diagnóstico por imagem , Pele/irrigação sanguínea , Animais , Pressão Sanguínea , Fluxometria por Laser-Doppler , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Análise de OndaletasRESUMO
BACKGROUND: To assess the safety profile, pharmacokinetics, pharmacodynamics and preliminary antitumour activity of fixed-dose SHR-1210, a novel anti-PD-1 antibody, in advanced solid tumours. METHODS: A total of 36 patients with advanced solid tumours received intravenous SHR-1210 at 60 mg, 200 mg and 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. The concentration of SHR-1210 was detected for pharmacokinetics, and receptor occupancy on circulating T lymphocytes was assessed for pharmacodynamics. RESULTS: No dose-limiting toxicities were observed. Maximum administered dose was not reached. Most adverse events were grade 1 or 2. Treatment-related severe adverse events were found in two patients. No treatment-related death was reported. Two complete responses (gastric cancer, bladder carcinoma) and seven partial responses were seen. In responders, the median follow-up time was 16.0 months (range 8.3-19.5), and the median duration of response was not reached (range 2.7-17.5+ months). The half-life of SHR-1210 was 2.94 d, 5.61 d and 11.0 d for 3 dose levels, respectively. CONCLUSIONS: Our results demonstrated a promising antitumour activity and a manageable safety profile of SHR-1210, displayed an explicit PK evidence of the feasibility of fixed dose, and established the foundation for further exploration.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Neoplasias/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: Islet microcirculation is mainly composed by IMECs. The aim of the study was to investigate the differences in gene expression profiles of IMECs upon glucose toxicity exposure and insulin treatment. METHODS: IMECs were treated with 5.6 mmol L-1 glucose, 35 mmol L-1 glucose, and 35 mmol L-1 glucose plus 10-8 mol L-1 insulin, respectively. Gene expression profiles were determined by microarray and verified by qPCR. GO terms and KEGG analysis were performed to assess the potential roles of differentially expressed genes. The interaction and expression tendency of differentially expressed genes were analyzed by Path-Net algorithm. RESULTS: Compared with glucose toxicity-exposed IMECs, 1574 mRNAs in control group and 2870 mRNAs in insulin-treated IMECs were identified with differential expression, respectively. GO and KEGG pathway analysis revealed that these genes conferred roles in regulation of apoptosis, proliferation, migration, adhesion, and metabolic process etc. Additionally, MAPK signaling pathway and apoptosis were the dominant nodes in Path-Net. IMECs survival and function pathways were significantly changed, and the expression tendency of genes from euglycemia and glucose toxicity exposure to insulin treatment was revealed and enriched in 7 patterns. CONCLUSIONS: Our study provides a microcirculatory framework for gene expression profiles of glucose toxicity-exposed IMECs.