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1.
Nature ; 591(7848): 66-71, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658693

RESUMO

The deep sea remains the largest unknown territory on Earth because it is so difficult to explore1-4. Owing to the extremely high pressure in the deep sea, rigid vessels5-7 and pressure-compensation systems8-10 are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths11-17. Here, inspired by the structure of a deep-sea snailfish15, we develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, we decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot's flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. We validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Our work highlights the potential of designing soft, lightweight devices for use in extreme conditions.

2.
Sensors (Basel) ; 22(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36298066

RESUMO

The issue of identity authentication for online medical services has been one of the key focuses of the healthcare industry in recent years. Most healthcare organizations use centralized identity management systems (IDMs), which not only limit the interoperability of patient identities between institutions of healthcare, but also create isolation between data islands. The more important matter is that centralized IDMs may lead to privacy disclosure. Therefore, we propose Health-zkIDM, a decentralized identity authentication system based on zero-knowledge proof and blockchain technology, which allows patients to identify and verify their identities transparently and safely in different health fields and promotes the interaction between IDM providers and patients. The users in Health-zkIDM are uniquely identified by one ID registered. The zero-knowledge proof technology is deployed on the client, which provides the user with a proof of identity information and automatically verifies the user's identity after registration. We implemented chaincodes on the Fabric, including the upload of proof of identity information, identification, and verification functions. The experiences show that the performance of the Health-zkIDM system can achieve throughputs higher than 400 TPS in Caliper.


Assuntos
Blockchain , Humanos , Atenção à Saúde , Privacidade , Tecnologia
3.
Chemistry ; 27(50): 12890-12899, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34288181

RESUMO

Chemical fixation of CO2 as C1 source at ambient temperature and low pressure is an energy-saving way to make use of the green-house gas, but it still remains a challenge since efficient catalyst with high catalytic active sites is required. Here, a novel monoclinic azo-functionalized Zr-based metal-organic polyhedron (Zr-AZDA) has been prepared and applied in CO2 fixation with epoxides. The inherent azo groups not only endow Zr-AZDA with good solubilization, but also act as basic sites to enrich CO2 showing efficient synergistic catalysis as confirmed by TPD-CO2 analysis. XPS results demonstrate that the Zr active sites in Zr-AZDA possess suitable Lewis acidity, which satisfies both substrates activation and products desorption. DFT calculation indicates the energy barrier of the rate-determining step in CO2 cycloaddition could be reduced remarkably (by ca. 60.9 %) in the presence of Zr-AZDA, which may rationalize the mild and efficient reaction condition employed (80 °C and 1 atm of CO2 ). The work provides an effective multi-functional cooperative method for improvement of CO2 cycloaddition.

4.
J Clin Pharm Ther ; 46(3): 599-609, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33543814

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The aim of this study was to systematically assess drug therapy in the guidelines for inflammatory bowel disease and to provide recommendations for the development of such guidelines. STUDY DESIGN: A systematic search was conducted in databases and on websites to identify guidelines for the treatment of inflammatory bowel disease. Qualified guidelines were assessed through the Appraisal of Guidelines for Research and Evaluation (AGREE II). Evidence from the guidelines was extracted from the guidelines themselves. The Oxford Centre for Evidence-based Medicine (OCEBM) evidence grading system was used to regrade and assess this evidence. RESULTS: A total of 11 guidelines for the medical treatment of inflammatory bowel disease (Crohn's disease and ulcerative colitis) (2015-2019) were finally included, and after scoring using the AGREE II tool, the median scores in each domain were as follows: Ⅰ. scope and purpose (median score=88.9%, range: 76.4%-91.7%), Ⅱ. stakeholder involvement (median =38.9%, range: 18.1%-61.1%), Ⅲ. rigour of development (median =69.3%, range: 39.6%-77.6%), Ⅳ. clarity and presentation (median =97.2%, range: 91.7%-100%), Ⅴ. applicability (median =45.8%, range: 24%-68.8%) and Ⅵ. editorial independence (median =94.0%, range: 0-100%). Most of the guidelines scored over 60%, which is worthy of clinical recommendation, but different guidelines suggest that there is a great difference in drug therapy, mainly due to various populations, diverse focuses of attention, distinct efficacy of drugs between Crohn's disease and ulcerative colitis, and the preference of guiding developers for select evidence. WHAT IS NEW AND CONCLUSION: The quality of medical treatment guidelines for inflammatory bowel disease varies considerably. Over the past 5 years, medical treatment has been heterogeneous among different guidelines. Consideration of factors leading to heterogeneity of recommendations for drug treatment, especially preferences for evidence selection, will help upgrade the guidelines.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Guias de Prática Clínica como Assunto , Corticosteroides/uso terapêutico , Ácidos Aminossalicílicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/fisiopatologia
5.
Int J Mol Sci ; 22(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34830071

RESUMO

Enhancing the phagocytosis of immune cells with medicines provides benefits to the physiological balance by removing foreign pathogens and apoptotic cells. The fungal immunomodulatory protein (FIP) possessing various immunopotentiation functions may be a good candidate for such drugs. However, the effect and mechanism of FIP on the phagocytic activity is limitedly investigated. Therefore, the present study determined effects of Cordyceps militaris immunomodulatory protein (CMIMP), a novel FIP reported to induce cytokines secretion, on the phagocytosis using three different types of models, including microsphere, Escherichia Coli and Candida albicans. CMIMP not only significantly improved the phagocytic ability (p < 0.05), but also enhanced the bactericidal activity (p < 0.05). Meanwhile, the cell size, especially the cytoplasm size, was markedly increased by CMIMP (p < 0.01), accompanied by an increase in the F-actin expression (p < 0.001). Further experiments displayed that CMIMP-induced phagocytosis, cell size and F-actin expression were alleviated by the specific inhibitor of TLR4 (p < 0.05). Similar results were observed in the treatment with the inhibitor of the NF-κB pathway (p < 0.05). In conclusion, it could be speculated that CMIMP promoted the phagocytic ability of macrophages through increasing F-actin expression and cell size in a TLR4-NF-κB pathway dependent way.


Assuntos
Cordyceps/química , Proteínas Fúngicas/farmacologia , Fatores Imunológicos/farmacologia , Macrófagos , NF-kappa B/imunologia , Fagocitose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/imunologia , Animais , Candida albicans/imunologia , Escherichia coli/imunologia , Proteínas Fúngicas/química , Fatores Imunológicos/química , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Células RAW 264.7 , Transdução de Sinais/imunologia
6.
Ecotoxicol Environ Saf ; 169: 370-375, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30466017

RESUMO

Modified nano-graphene quantum dots (M-GQDs) are widely used in bioimaging, drug delivery, and chemical engineering. Because M-GQDs could induce reactive oxygen species and DNA damage, we hypothesized that M-GQDs modulate DNA methylation. To test this hypothesis, zebrafish were exposed to reduced, hydroxylated, or aminated GQDs (graphene quantum dots) at different concentrations for 7 days; global DNA methylation in liver, gill, and intestine was then studied. M-GQDs induced global DNA hypermethylation in various tissues in a dose-dependent manner. The global DNA methylation of reduced and aminated GQDs exposure showed a significant increase in intestines even at low concentrations (2 mg/L), suggesting that intestines are the main target for these two M-GQDs. The effects of global DNA methylation were evaluated 14 days after exposure had ceased. DNA methylation in the livers of exposure groups was significantly higher than in control zebrafish. Global DNA methylation increased in livers of zebrafish even after exposure to aminated GQDs (2 mg/L) had ceased, indicating a more complex mechanism of DNA methylation deregulation. The present results showed that chemical groups in the surface of GQDs are a critical factor for modulating DNA methylation.


Assuntos
Metilação de DNA , Grafite/toxicidade , Pontos Quânticos/toxicidade , Peixe-Zebra/metabolismo , Animais , Relação Dose-Resposta a Droga , Grafite/análise , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pontos Quânticos/análise , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Testes de Toxicidade
7.
Ecotoxicol Environ Saf ; 167: 76-82, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30308403

RESUMO

Samples of soil, earthworms, and tree roots from the forest ecosystem in the Dexing Pb/Zn mining area of Jiangxi Province were collected and the status of trace metal pollution analyzed to assess potential ecological risks. Chemometric and geographic information system methods were used to identify and describe the spatial distributions and the main contamination sources of trace metals. The order of potential ecological risks of trace metals in this area are as follows: cadmium (Cd) > arsenic (As) > copper (Cu) > nickel (Ni) > lead (Pb) > chromium (Cr) > zinc (Zn). Elemental spatial distribution maps showed the existence of zones heavily polluted by trace metals around the mining area. Earthworms and roots of three tree species were also heavily contaminated, with concentrations of trace metals in earthworms much higher than in previous studies. The potential ecological risk index and other soil quality indices indicated that soil had moderate to severe contamination and there were high ecological risks, with Cd making the greatest contribution. Multivariate statistical analyses showed that Cd, As, Cu, Pb, and Zn in soil came from a mining activity source, whereas Ni and Cr primarily originated from a natural source.


Assuntos
Florestas , Metais Pesados/análise , Mineração , Poluentes do Solo/análise , Animais , China , Monitoramento Ambiental , Sistemas de Informação Geográfica , Análise Multivariada , Oligoquetos/química , Raízes de Plantas/química , Medição de Risco , Solo/química , Árvores/química
8.
Environ Geochem Health ; 41(2): 967-980, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30264359

RESUMO

Surface agricultural soil samples obtained from Dexing Pb/Zn mining area in Jiangxi province were analyzed for trace metals to assess their pollution status and potential ecological risk. The spatial distributions and the major trace metals pollution sources were described and identified with the combination of chemical measures and geographic information systems technology. The level of pollution in seven metals is decreasing in the following order: zinc (Zn 128.9 mg/kg) > chromium (Cr 64.1 mg/kg) > lead (Pb 58.4 mg/kg) > arsenic (As 45.3 mg/kg) > copper (Cu 41.9 mg/kg) > nickel (Ni 31.3 mg/kg) > cadmium (Cd 1.5 mg/kg). Trace metal spatial distribution maps established by geographic information system techniques displayed two high-pollution zones around mining sites in the study area. Multivariate statistical analyses were also applied, and the results demonstrated that Cd, As, Pb, Cu and Zn in the soils originated from mining activities, whereas Cr and Ni primarily originated from natural sources. The values of pollution index ranged from 4.79 to 71.59, and the values of modified pollution index ranged from 1.98 to 24.69. Moreover, the potential ecological risk values ranged from 264.0 to 3263.5, which indicated considerable ecological risk to very high ecological risk. The potential ecological risk values and other soil contamination indices showed similar patterns that the high-risk areas were around Dexing Pb/Zn mining site. The surface agricultural soil in study area is heavily to extremely polluted , with Cd that made the most dominant contribution.


Assuntos
Metais Pesados/análise , Poluentes do Solo/análise , Agricultura , China , Monitoramento Ambiental/métodos , Sistemas de Informação Geográfica , Chumbo/análise , Mineração , Análise Multivariada , Medição de Risco , Zinco/análise
9.
Mikrochim Acta ; 185(10): 473, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30242509

RESUMO

A molecularly imprinted polymer (MIP) was fabricated for selective recognition of the highly persistent pollutant perfluorooctane sulfonate (PFOS). The MIP was prepared from chitosan and doped with fluorescent carbon quantum dots (CQDs). It was characterized by fluorescence spectrophotometry, scanning electron microscopy, and Fourier transform infrared spectroscopy. The fluorescence of the CQDs, best measured at excitation/emission wavelengths of 350/460 nm, is enhanced by PFOS, and the effect is much stronger for the MIP than for the nonimprinted polymer (NIP). The imprinting factor is 2.75. The method has good specificity over sodium dodecyl sulfate (SDS), perfluorooctanoic acid (PFOA), sodium dodecyl sulfonate (SDS'), sodium dodecyl benzene sulfonate (SDBS), perfluorooctanesulfonyl fluoride (POSF), perfluorobutane sulfonate (PFBS) and 1-octanesulfonic acid sodium (OSA). Fluorescence increases linearly in the 20-200 pg·L-1 POSF concentration range in aqueous solution. The method was applied to the determination of PFOS in spiked serum and urine samples. The limits of detection are 66 and 85 pg·L-1 for serum and urine samples respectively. The recoveries ranged from to 81-98%, with relative standard deviations in the range of 1.8-8.2%. Compared with LC-MS/MS, this assay is more convenient since the material can be prepared flexibly and the method can be applied on-site. Graphical abstract Schematic of the fabrication of a molecularly imprinted chitosan hydrogel doped with CQDs for selective fluorometric determination of PFOS. a. The photo of chitosan hydrogel. b, c, d, e represents the hydrogel observed under UV lamp. b', c', d', e' represents the inner structure of hydrogel bead.

10.
Angew Chem Int Ed Engl ; 57(32): 10168-10172, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-29947070

RESUMO

Ambient-temperature sodium-sulfur (Na-S) batteries are considered a promising energy storage system due to their high theoretical energy density and low costs. However, great challenges remain in achieving a high rechargeable capacity and long cycle life. Herein we report a stable quasi-solid-state Na-S battery enabled by a poly(S-pentaerythritol tetraacrylate (PETEA))-based cathode and a (PETEA-tris[2-(acryloyloxy)ethyl] isocyanurate (THEICTA))-based gel polymer electrolyte. The polymeric sulfur electrode strongly anchors sulfur through chemical binding and inhibits the shuttle effect. Meanwhile, the in situ formed polymer electrolyte with high ionic conductivity and enhanced safety successfully stabilizes the Na anode/electrolyte interface, and simultaneously immobilizes soluble Na polysulfides. The as-developed quasi-solid-state Na-S cells exhibit a high reversible capacity of 877 mA h g-1 at 0.1 C and an extended cycling stability.

11.
J Nanosci Nanotechnol ; 17(2): 1133-139, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29676879

RESUMO

In this work, the morphology and properties of graphene modified natural rubber (NR) was studied. Graphite oxide was chemically reduced with poly(sodium 4-styrenesulfonate) as a stabilizer, then the obtained graphene was blended with NR using latex technique. It is observed that a stable graphene suspension was fabricated by chemical reduction of graphite oxide in the presence of surfactant, while graphene was dispersed homogeneous in NR matrix as tested by WAXD and TEM. Dynamic mechanical analysis showed that storage modulus enhanced dramatically after the incorporation of graphene due to the high surface area of graphene and the exfoliated structure of graphene in NR. The electrical property and thermal conductive properties of NR/graphene nanocomposites improved significantly following the increase in graphene concentration.

12.
Int J Mol Sci ; 18(11)2017 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-29156556

RESUMO

Caudal type homeobox 2 (CDX2) is expressed in intestinal epithelial cells and plays a role in gut development and homeostasis by regulating cell proliferation. However, whether CDX2 cooperates with the mammalian target of rapamycin complex 1 (mTORC1) and Wnt/ß-catenin signaling pathways to stimulate cell proliferation remains unknown. The objective of this study was to investigate the effect of CDX2 on the proliferation of porcine jejunum epithelial cells (IPEC-J2) and the correlation between CDX2, the mTORC1 and Wnt/ß-catenin signaling pathways. CDX2 overexpression and knockdown cell culture models were established to explore the regulation of CDX2 on both pathways. Pathway-specific antagonists were used to verify the effects. The results showed that CDX2 overexpression increased IPEC-J2 cell proliferation and activated both the mTORC1 and Wnt/ß-catenin pathways, and that CDX2 knockdown decreased cell proliferation and inhibited both pathways. Furthermore, the mTORC1 and Wnt/ß-catenin pathway-specific antagonist rapamycin and XAV939 (3,5,7,8-tetrahydro-2-[4-(trifluoromethyl)]-4H -thiopyrano[4,3-d]pyrimidin-4-one) both suppressed the proliferation of IPEC-J2 cells overexpressing CDX2, and that the combination of rapamycin and XAV939 had an additive effect. Regardless of whether the cells were treated with rapamycin or XAV939 alone or in combination, both mTORC1 and Wnt/ß-catenin pathways were down-regulated, accompanied by a decrease in CDX2 expression. Taken together, our data indicate that CDX2 stimulates porcine intestinal epithelial cell proliferation by activating the mTORC1 and Wnt/ß-catenin signaling pathways.


Assuntos
Fator de Transcrição CDX2/genética , Células Epiteliais/citologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Via de Sinalização Wnt , Animais , Fator de Transcrição CDX2/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Compostos Heterocíclicos com 3 Anéis/farmacologia , Sirolimo/farmacologia , Suínos , Via de Sinalização Wnt/efeitos dos fármacos
13.
Development ; 140(13): 2755-64, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23698347

RESUMO

Multiciliated cells (MCCs) possess multiple motile cilia and are distributed throughout the vertebrate body, performing important physiological functions by regulating fluid movement in the intercellular space. Neither their function during organ development nor the molecular mechanisms underlying multiciliogenesis are well understood. Although dysregulation of members of the miR-34 family plays a key role in the progression of various cancers, the physiological function of miR-34b, especially in regulating organ formation, is largely unknown. Here, we demonstrate that miR-34b expression is enriched in kidney MCCs and the olfactory placode in zebrafish. Inhibiting miR-34b function using morpholino antisense oligonucleotides disrupted kidney proximal tubule convolution and the proper distribution of distal transporting cells and MCCs. Microarray analysis of gene expression, cilia immunostaining and a fluid flow assay revealed that miR-34b is functionally required for the multiciliogenesis of MCCs in the kidney and olfactory placode. We hypothesize that miR-34b regulates kidney morphogenesis by controlling the movement and distribution of kidney MCCs and fluid flow. We found that cmyb was genetically downstream of miR-34b and acted as a key regulator of multiciliogenesis. Elevated expression of cmyb blocked membrane docking of centrioles, whereas loss of cmyb impaired centriole multiplication, both of which resulted in defects in the formation of ciliary bundles. Thus, miR-34b serves as a guardian to maintain the proper level of cmyb expression. In summary, our studies have uncovered an essential role for miR-34b-Cmyb signaling during multiciliogenesis and kidney morphogenesis.


Assuntos
MicroRNAs/fisiologia , Animais , Movimento Celular/genética , Movimento Celular/fisiologia , Rim/embriologia , Rim/metabolismo , MicroRNAs/genética , Reação em Cadeia da Polimerase , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
14.
Blood ; 124(8): 1320-30, 2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-24990885

RESUMO

Neutrophils play critical roles in vertebrate innate immune responses. As an emerging regulator in normal myelopoiesis, the precise roles of microRNA in the development of neutrophils have yet to be clarified. Using zinc-finger nucleases, we have successfully generated heritable mutations in miR-142a and miR-142b and showed that hematopoietic-specific miR-142-3p is completely deleted in miR-142 double mutant zebrafish. The lack of miR-142-3p resulted in aberrant reduction and hypermaturation of neutrophils in definitive myelopoiesis, as well as impaired inflammatory migration of neutrophils in the fetal stage. Furthermore, the adult myelopoiesis in the miR-142-3p-deficient zebrafish was also affected, producing irregular hypermature neutrophils with increased cell size and a decreased nucleocytoplasmic ratio. Additionally, miR-142-3p-deficient zebrafish are expected to develop a chronic failure of myelopoiesis with age. Transcriptome analysis showed an aberrant activation of the interferon γ (IFN-γ) signaling pathway in myelomonocytes after miR-142-3p deletion. We found that the reduced number and hypermaturation of neutrophils caused by loss of miR-142-3p was mainly mediated by the abnormally activated IFN-γ signaling, especially the upregulation of stat1a and irf1b. Taken together, we uncovered a novel role of miR-142-3p in maintaining normal neutrophil development and maturation.


Assuntos
MicroRNAs/metabolismo , Mielopoese/fisiologia , Neutrófilos/metabolismo , Transdução de Sinais/fisiologia , Peixe-Zebra/metabolismo , Animais , Deleção de Genes , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , MicroRNAs/genética , Neutrófilos/citologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Transcriptoma , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
15.
Biol Pharm Bull ; 39(5): 762-9, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26935150

RESUMO

To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t1/2, peak concentration (Cmax), the area of concentration-time curve from 0 to 6 h (AUC0-6 h) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of Cmax and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69- and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.


Assuntos
Sistemas de Liberação de Medicamentos , Flavonas/administração & dosagem , Flavonas/farmacocinética , Pueraria , Administração Oral , Animais , Liberação Controlada de Fármacos , Emulsões , Flavonas/sangue , Flavonas/química , Masculino , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Comprimidos
16.
Dev Biol ; 392(2): 233-44, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24892953

RESUMO

As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity. Furthermore, we found that Setdb2 functions through fine-tuning the expression of dvr1, a ligand of the TGF-ß superfamily, to an appropriate level to ensure proper C&E movements in a non-cell-autonomous manner. In addition, both overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E movements and acts by modulating the expression level of dvr1, suggesting that Dvr1 acts as a direct and essential mediator for C&E cell movements.


Assuntos
Movimento Celular/fisiologia , Gastrulação/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Histona-Lisina N-Metiltransferase/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/embriologia , Animais , Western Blotting , Imunofluorescência , Técnicas de Silenciamento de Genes , Histona Metiltransferases , Histona-Lisina N-Metiltransferase/metabolismo , Hibridização In Situ , Análise em Microsséries , Morfolinos/genética , Reação em Cadeia da Polimerase em Tempo Real , Fator de Crescimento Transformador beta/genética , Proteínas de Peixe-Zebra/genética
17.
Mol Pharm ; 12(1): 1-9, 2015 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-25389765

RESUMO

P-glycoprotein (P-gp)-mediated drug-drug interactions are important factors causing adverse effects of drugs in clinical use. The aim of this study was to determine whether trantinterol (also known as SPFF), a novel ß2-adrenoceptor agonist, was a P-gp inhibitor or substrate. The results showed that trantinterol was not a substrate of P-gp but increased rhodamine 123 (Rho 123) uptake by MDCK-MDR1 cells and decreased the efflux transport of both Rho 123 and cyclosporine A (CsA) in bidirectional transport studies across MDCK-MDR1 cell monolayers. This suggested that trantinterol was a P-gp inhibitor but not a P-gp substrate. The mechanism of inhibition was investigated in the P-gp-Glo assay system, where it was found that trantinterol inhibited P-gp ATPase activity in a dose-dependent manner. A subsequent study using the antibody binding assay with the conformation-sensitive P-gp-specific antibody UIC2 confirmed that trantinterol decreased UIC2 binding at 10 µM in contrast to the competitive inhibitor, verapamil. This suggested that trantinterol was a noncompetitive inhibitor of P-gp. Finally, a pharmacokinetic study in rat showed that trantinterol significantly increased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) of digoxin and paclitaxel (PAC), and the Cmax of cyclosporine A (CsA). In summary, trantinterol is a potent noncompetitive P-gp inhibitor which may increase the bioavailability of other P-gp substrate drugs coadministered with it.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Agonistas Adrenérgicos beta/química , Clembuterol/análogos & derivados , Adenosina Trifosfatases/química , Animais , Anticorpos Monoclonais/química , Área Sob a Curva , Sítios de Ligação , Transporte Biológico , Células CACO-2 , Clembuterol/química , Ciclosporina/química , Digoxina/química , Cães , Avaliação Pré-Clínica de Medicamentos , Humanos , Células Madin Darby de Rim Canino , Masculino , Paclitaxel/química , Ratos , Ratos Wistar , Rodamina 123/química
18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 32(4): 815-20, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26710453

RESUMO

Medical information exchange and integration is the effective method to solve the interoperability and medical information island, and is the basis of medical information sharing. In this paper, we take medical texts and medical images as the basic integrated objects, DICOM, HL7 messages and datasets as the integrated units, efficient DI-COM, HL7 message construction and parsing methods as basis, design and realize a universal medical information integration and exchange service middleware. Experimental results show that the prototype system could perform medical information integration and exchange among relational database, HL7 and DICOM message, provide a feasible scheme to solve the medical information island and lay a good foundation for establishing the unified medical information integration and sharing platform. The middleware has been applied in the project named "development and demonstration of opened medical information integration system".


Assuntos
Sistemas Computacionais , Informática Médica , Disseminação de Informação , Software
19.
J Biol Chem ; 288(19): 13551-62, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23539630

RESUMO

BACKGROUND: The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. RESULTS: Cnr2 activation down-regulates 5-lipoxygenase (Alox5) expression by suppressing the JNK/c-Jun activation. CONCLUSION: The Cnr2-JNK-Alox5 axis modulates leukocyte inflammatory migration. SIGNIFICANCE: Linking two important regulators in leukocyte inflammatory migration and providing a potential therapeutic strategy for treating human inflammation-associated diseases. Inflammatory migration of immune cells is involved in many human diseases. Identification of molecular pathways and modulators controlling inflammatory migration could lead to therapeutic strategies for treating human inflammation-associated diseases. The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. Through a chemical genetic screen using a zebrafish model for leukocyte migration, we found that both an agonist of the Cnr2 and inhibitor of the 5-lipoxygenase (Alox5, encoded by alox5) inhibit leukocyte migration in response to acute injury. These agents have a similar effect on migration of human myeloid cells. Consistent with these results, we found that inactivation of Cnr2 by zinc finger nuclease-mediated mutagenesis enhances leukocyte migration, while inactivation of Alox5 blocks leukocyte migration. Further investigation indicates that there is a signaling link between Cnr2 and Alox5 and that alox5 is a target of c-Jun. Cnr2 activation down-regulates alox5 expression by suppressing the JNK/c-Jun activation. These studies demonstrate that Cnr2, JNK, and Alox5 constitute a pathway regulating leukocyte migration. The cooperative effect between the Cnr2 agonist and Alox5 inhibitor also provides a potential therapeutic strategy for treating human inflammation-associated diseases.


Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Movimento Celular/efeitos dos fármacos , Leucócitos/fisiologia , Sistema de Sinalização das MAP Quinases , Receptor CB2 de Canabinoide/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Araquidonato 5-Lipoxigenase/genética , Sequência de Bases , Agonistas de Receptores de Canabinoides/farmacologia , Regulação Enzimológica da Expressão Gênica , Técnicas de Inativação de Genes , Indóis/farmacologia , Leucócitos/efeitos dos fármacos , Dados de Sequência Molecular , Ligação Proteica , Proteínas Proto-Oncogênicas c-jun/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Cauda , Imagem com Lapso de Tempo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
20.
Math Biosci Eng ; 20(9): 16060-16082, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37920003

RESUMO

The purpose of infrared and visible image fusion is to integrate the complementary information from heterogeneous images in order to enhance their detailed scene information. However, existing deep learning fusion methods suffer from an imbalance between fusion performance and computational resource consumption. Additionally, fusion layers or fusion rules fail to effectively combine heteromodal feature information. To address these challenges, this paper presents a novel algorithm called infrared and visible image fusion network base on fast edge convolution (FECFusion). During the training phase, the proposed algorithm enhances the extraction of texture features in the source image through the utilization of structural re-parameterization edge convolution (RECB) with embedded edge operators. Subsequently, the attention fusion module (AFM) is employed to sufficiently fuze both unique and public information from the heteromodal features. In the inference stage, we further optimize the training network using the structural reparameterization technique, resulting in a VGG-like network architecture. This optimization improves the fusion speed while maintaining the fusion performance. To evaluate the performance of the proposed FECFusion algorithm, qualitative and quantitative experiments are conducted. Seven advanced fusion algorithms are compared using MSRS, TNO, and M3FD datasets. The results demonstrate that the fusion algorithm presented in this paper achieves superior performance in multiple evaluation metrics, while consuming fewer computational resources. Consequently, the proposed algorithm yields better visual results and provides richer scene detail information.

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