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1.
Heliyon ; 9(6): e16603, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37332904

RESUMO

Gas extraction is an important way to solve coal mine gas in China. At present, the development of new and more efficient gas sealing materials is an urgent problem in China's coal mining industry. In order to improve the gas extraction efficiency and promote the development and utilization of coalbed methane, we developed a new inorganic slow setting material which used bentonite as main material. We added two kinds of organic modified materials and two kinds of inorganic modified materials to optimize the sealing performance, and analyzed the viscosity, sealing and particle size changes after modification. The rheological properties and diffusion properties of sealing materials was studied. Meanwhile, field experiments were carried out to verify that it has more efficient sealing performance than traditional cement materials and could improves the efficiency of gas drainage and reduces mine gas disaster accidents.

2.
Materials (Basel) ; 15(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36079226

RESUMO

Electrode materials are key factors for supercapacitors to endow them with excellent electrochemical properties. Here, a novel hybrid structure of a CoSe/Co3O4-CNTs binder free composite electrode on nickel foam was prepared via a facile flame method, followed by an electrodeposition process. Benefitting from the synergetic effects of the multicomponent (with low resistances of 1.542 Ω cm2 and a moderate mesoporous size of 3.12 nm) and the enlarged specific surface area of the composite material (77.4 m2 g-1), the CoSe/Co3O4-CNTs composite electrode delivers a high specific capacitance of 2906 F g-1 at 5 mV s-1 with an excellent rate stability. The fabricated CoSe/Co3O4-CNTs/NF//AC ASC exhibits a high energy density of 43.4 Wh kg-1 at 0.8 kW kg-1 and a long cycle life (92.7% capacitance retention after 10,000 cycles).

3.
Small ; 18(14): e2106657, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35023632

RESUMO

Mapping technique has been the powerful tool for the design of next-generation energy storage devices. Unlike the traditional ion-insertion based lithium batteries, the Li-S battery is based on the complex conversion reactions, which require more cooperation from mapping techniques to elucidate the underlying mechanism. Therefore, in this review, the representative works of mapping techniques for Li-S batteries are summarized, and categorized into the studies of lithium metal anode and sulfur cathode, with sub-sections based on shared characterization mechanisms. Due to specific features of mapping techniques, various aspects such as compositional distribution, in-plain/cross section characterization, coin cell/pouch cell configuration, and structural/mechanical analysis are emphasized in each study, aiming for the guidance for developing strategies to improve the battery performances. Benefited from the achieved progresses, suggestions for future studies based on mapping techniques are proposed to accelerate the development and commercialization of the Li-S battery.

4.
ACS Appl Mater Interfaces ; 13(21): 24833-24855, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34014637

RESUMO

Sr0.7Bi0.2TiO3 (SBT) is a promising pulse energy storage material due to minor hysteresis, but its low maximum polarization (Pmax) is bad for energy storage. K+-Bi3+ defect pairs were introduced into the A-site of SBT to obtain Sr0.35Bi0.35K0.25TiO3 (SBKT) with larger Pmax. Through first-principles calculations, we determined that the introduction of defect pairs destroys the paraelectric order phase and increases local polarization, resulting in more and larger polar nanoregion (PNR) formation. On this basis, doping NaNbO3 (NN) in A- and B-sites of SBKT increases the cationic disorder and ferroelectric destabilization, further destroying the long-range order structure and forming more PNRs with smaller sizes. This enhances relaxation and decreases remnant polarization, and the broadened dielectric peak enables 0.85SBKT-0.15NN to meet the X7R specification. Furthermore, the decreased grain size and oxygen vacancy, increased thermal conductivity, and weakened local electric field (simulated by COMSOL) increase the dielectric breakdown strength (BDS). As a result, 0.95SBKT-0.05NN exhibits a high energy storage density (W) of 2.45 J/cm3 with a high efficiency of 93.1%, a high pulsed discharge energy density of 2.1 J/cm3, and a high power density of 54.1 MW/cm3 at 220 kV/cm. The energy storage properties show excellent stability of temperature (-55 to 150 °C), frequency (10-500 Hz), and cycling (105 cycles). Notably, for the pulse charge-discharge properties, 0.95SBKT-0.05NN shows great fatigue resistance during 105 cycles under 25 and 150 °C, accompanied by excellent thermal stability. Moreover, the BDS and Pmax of 0.95SBKT-0.05NN sintered in O2 further enhance. A higher W of 2.92 J/cm3 with a high efficiency of 89% at 250 kV/cm is achieved. Therefore, 0.95SBKT-0.05NN shows great application potential for pulse energy storage. In this work, we provide a novel strategy and systematic in-depth study for improving the energy storage properties of SBT.

5.
J Gen Physiol ; 153(4)2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33651884

RESUMO

Adrenal chromaffin cells (CCs) in rodents express rapidly inactivating, tetrodotoxin (TTX)-sensitive sodium channels. The resulting current has generally been attributed to Nav1.7, although a possible role for Nav1.3 has also been suggested. Nav channels in rat CCs rapidly inactivate via two independent pathways which differ in their time course of recovery. One subpopulation recovers with time constants similar to traditional fast inactivation and the other ∼10-fold slower, but both pathways can act within a single homogenous population of channels. Here, we use Nav1.3 KO mice to probe the properties and molecular components of Nav current in CCs. We find that the absence of Nav1.3 abolishes all Nav current in about half of CCs examined, while a small, fast inactivating Nav current is still observed in the rest. To probe possible molecular components underlying slow recovery from inactivation, we used mice null for fibroblast growth factor homology factor 14 (FGF14). In these cells, the slow component of recovery from fast inactivation is completely absent in most CCs, with no change in the time constant of fast recovery. The use dependence of Nav current reduction during trains of stimuli in WT cells is completely abolished in FGF14 KO mice, directly demonstrating a role for slow recovery from inactivation in determining Nav current availability. Our results indicate that FGF14-mediated inactivation is the major determinant defining use-dependent changes in Nav availability in CCs. These results establish that Nav1.3, like other Nav isoforms, can also partner with FGF subunits, strongly regulating Nav channel function.


Assuntos
Células Cromafins , Sódio , Animais , Fatores de Crescimento de Fibroblastos/genética , Camundongos , Canal de Sódio Disparado por Voltagem NAV1.3 , Ratos , Bloqueadores dos Canais de Sódio , Tetrodotoxina/farmacologia
6.
Small ; 15(35): e1901980, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31267654

RESUMO

As one important electrode reaction in electrocatalytic and photoelectrochemical cells for renewable energy circulation, oxygen catalysis has attracted considerable research in developing efficient and cost-effective catalysts. Due to the inevitable formation of oxygenic intermediates on surface sites during the complex reaction steps, the surface structure dynamically evolves toward reaction-preferred active species. To date, transition metal compounds, here defined as TM-Xides, where "X" refers to typical nonmetal elements from group IIIA to VIA, including hydroxide as well, are reported as high-performance oxygen evolution reaction (OER) electrocatalysts. However, more studies observe at least exterior oxidation or amorphization of materials. Thus, whether the TM-Xides can be defined as OER catalysts deserves further discussion. This Review pays attention to recent progress on the surface reconstruction of TM-Xide OER electrocatalysts with an emphasis on the identification of the true active species for OER, and aims at disseminating the real contributors of OER performance, especially under long-duration electrocatalysis.

7.
Nat Commun ; 10(1): 881, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787325

RESUMO

Red blood cells mature within the erythroblastic island (EI) niche that consists of specialized macrophages surrounded by differentiating erythroblasts. Here we establish an in vitro system to model the human EI niche using macrophages that are derived from human induced pluripotent stem cells (iPSCs), and are also genetically programmed to an EI-like phenotype by inducible activation of the transcription factor, KLF1. These EI-like macrophages increase the production of mature, enucleated erythroid cells from umbilical cord blood derived CD34+ haematopoietic progenitor cells and iPSCs; this enhanced production is partially retained even when the contact between progenitor cells and macrophages is inhibited, suggesting that KLF1-induced secreted proteins may be involved in this enhancement. Lastly, we find that the addition of three secreted factors, ANGPTL7, IL-33 and SERPINB2, significantly enhances the production of mature enucleated red blood cells. Our study thus contributes to the ultimate goal of replacing blood transfusion with a manufactured product.


Assuntos
Eritroblastos/citologia , Eritrócitos/citologia , Eritropoese/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Fatores de Transcrição Kruppel-Like/metabolismo , Macrófagos/citologia , Proteína 7 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/metabolismo , Antígenos CD34/metabolismo , Substitutos Sanguíneos/uso terapêutico , Transfusão de Sangue , Células-Tronco Hematopoéticas/citologia , Humanos , Interleucina-33/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Inibidor 2 de Ativador de Plasminogênio/metabolismo
8.
ACS Omega ; 3(9): 11033-11040, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31459213

RESUMO

We investigated the structure and antireduction of Ti4+ in orthorhombic perovskite Ca0.61Nd0.26TiO3 (CNT) ceramic by doping with three different additives (Cr2O3, MnO2, and SnO2). The X-ray diffraction patterns showed that the main phase of orthorhombic perovskite was formed in all the samples. In addition, the substitution of M (M = Cr3+, Mn4+, Sn4+) for Ti4+ resulted in the oxygen octahedral distortion and changes of order degree of B-site, which was confirmed by Raman spectra. The εr and τf values were concerned with the average ionicity of B-O bond f i(B-ave) and the linear expansion coefficient α, respectively. The X-ray photoelectron spectra indicated that three different additives could restrain the reduction of Ti4+, which was beneficial to the improvement of the Q × f value for CNT ceramic. High Q × f value of 16 123 GHz was obtained in the CNT + 1 mol % Cr2O3 ceramic compared with Q × f value of 11 207 GHz in pure CNT ceramic.

9.
Chemistry ; 24(17): 4390-4398, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29230886

RESUMO

A facile calcination method is developed for the in situ synthesis of nanohybrids of Ti3+ self-doped TiO2 /graphene quantum dot nanosheets (Ti3+ -TiO2 /GQD NSs). Ti3+ sites are formed on the surface of the TiO2 nanosheets through carbothermal reduction by GQDs, using citric acid as a carbon source. Such heterojunctions exhibit enhanced visible-light absorption properties, large photocurrent current densities, and low recombination of photoinduced carriers. The methylene blue (MB) and rhodamine B (RhB) photodegradation result demonstrates a higher visible-light photocatalysis performance than that of the original TiO2 . On one hand, inducing Ti3+ sites is efficient for the separation of photogenerated charge carriers and for reducing electron-hole pair recombination. On the other hand, GQDs are beneficial for generating more photocurrent carriers and facilitating the charge transfer across the TiO2 surface. It is proposed that Ti3+ sites and GQDs induced in TiO2 nanosheets have a synergistic effect, leading to excellent photocatalysis properties. Finally, a theoretical calculation is provided of the carbothermal reduction for the formation mechanism of the Ti3+ defect sites.

10.
Proc Natl Acad Sci U S A ; 114(18): E3739-E3747, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28416688

RESUMO

Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca2+, suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KO mice with a ß-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons. We establish the presence of LRRC26 protein in eight secretory tissues or tissues with significant secretory epithelium and show that LRRC26 protein coassembles with the pore-forming BK α-subunit in at least three tissues: lacrimal gland, parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar cells, LRRC26 KO shifts BK gating to be like α-subunit-only BK channels. Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva. LRRC26-containing BK channels are competent to contribute to resting K+ efflux at normal cell membrane potentials with resting cytosolic Ca2+ concentrations and likely play a critical physiological role in supporting normal secretory function in all secretory epithelial cells.


Assuntos
Colo/metabolismo , Células Epiteliais/metabolismo , Aparelho Lacrimal/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Potenciais da Membrana , Glândula Parótida/metabolismo , Animais , Cálcio/metabolismo , Colo/citologia , Células Epiteliais/citologia , Aparelho Lacrimal/citologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Camundongos , Camundongos Knockout , Glândula Parótida/citologia , Potássio/metabolismo
11.
Stem Cells ; 35(4): 886-897, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28026072

RESUMO

Blood transfusion is widely used in the clinic but the source of red blood cells (RBCs) is dependent on donors, procedures are susceptible to transfusion-transmitted infections and complications can arise from immunological incompatibility. Clinically-compatible and scalable protocols that allow the production of RBCs from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been described but progress to translation has been hampered by poor maturation and fragility of the resultant cells. Genetic programming using transcription factors has been used to drive lineage determination and differentiation so we used this approach to assess whether exogenous expression of the Erythroid Krüppel-like factor 1 (EKLF/KLF1) could augment the differentiation and stability of iPSC-derived RBCs. To activate KLF1 at defined time points during later stages of the differentiation process and to avoid transgene silencing that is commonly observed in differentiating pluripotent stem cells, we targeted a tamoxifen-inducible KLF1-ERT2 expression cassette into the AAVS1 locus. Activation of KLF1 at day 10 of the differentiation process when hematopoietic progenitor cells were present, enhanced erythroid commitment and differentiation. Continued culture resulted the appearance of more enucleated cells when KLF1 was activated which is possibly due to their more robust morphology. Globin profiling indicated that these conditions produced embryonic-like erythroid cells. This study demonstrates the successful use of an inducible genetic programing strategy that could be applied to the production of many other cell lineages from human induced pluripotent stem cells with the integration of programming factors into the AAVS1 locus providing a safer and more reproducible route to the clinic. Stem Cells 2017;35:886-897.


Assuntos
Diferenciação Celular , Eritrócitos/citologia , Eritrócitos/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Fatores de Transcrição Kruppel-Like/metabolismo , Núcleo Celular/metabolismo , Proliferação de Células , Eritropoese/genética , Regulação da Expressão Gênica , Globinas/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Células K562 , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-27642359

RESUMO

Xerostomia is one of the most common acute and late complications of radiotherapy for head and neck cancer, and it affects quality of life. We conducted a prospective study to evaluate the efficacy of traditional Chinese medicine (TCM) in toxicities and quality of life during radiotherapy. Head and neck cancer patients who were scheduled for radiotherapy were checked for inclusion/exclusion criteria before enrollment. Patients in the study group (inpatients) were hospitalized in a Chinese medicine ward and received concomitant TCM intervention during radiotherapy, while those in the control group (outpatients) received only conventional cancer treatments at the Western outpatient department. The primary end point was amelioration of postradiotherapy side effects. The secondary end points were quality of life during the cancer therapy and occurrence of adverse events following the TCM treatments. Thirty inpatients and 50 outpatients completed the study. Compared to the control group, those in the TCM group had decreased severity of xerostomia. There was no treatment-related impairment of renal or hepatic function among TCM group. Although better outcomes of social contact, dyspnea, physical and emotional function, and financial problems were found in the TCM group, we need further confirmation about the impact of hospitalization itself on these results.

13.
J Nanosci Nanotechnol ; 16(3): 2866-71, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27455722

RESUMO

To solve some problems existing in PZT films, such as: large residual stresses, interface diffusion, and lead loss, etc., which were caused by high post-annealing temperatures, and to obtain thin films with high-preferred orientation and uniform size grain and dense microstructure, different technological conditions of microwave plasma assisted post-annealing had been pilot studied. X-ray diffraction was used to analyze the crystal structures of the films. Transmission electronic microscope was used to analyze the surface and the interface morphology of the films. Ferroelectric properties were showed by measuring the remnant polarization and the leakage current dependence of electric field. The results indicated that it was good for reducing lead loss and annealing temperature of PZT films by microwave plasma assisted annealing. Ferroelectric properties of the film could also be enhanced by this pilot annealing method.


Assuntos
Metais/química , Micro-Ondas , Humanos
14.
Int J Rheum Dis ; 19(9): 880-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25940989

RESUMO

AIM: To compare the diagnostic performance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) in the diagnosis of patients with rheumatoid arthritis (RA) in Taiwan. METHODS: Serum concentrations of RF and anti-CCP were measured in 246 cases, including 39 patients with RA and 207 patients with other rheumatic diseases (non-RA). The age, sex, clinical presentation, RF, anti-CCP results and the final diagnoses were recorded and analyzed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were calculated. RESULTS: Among all 246 patients, 39 (15.9%) were diagnosed with RA and 207 (84.1%) were diagnosed with other rheumatic diseases (non-RA). In the diagnosis of RA, the sensitivity, specificity, PPV, NPV, LR+ and LR- of the RF test were 67%, 79%, 37%, 93%, 3.12, and 0.42, respectively. The corresponding data for the anti-CCP test were 79%, 98%, 86%, 96%, 32.91 and 0.21, respectively. The presence of either anti-CCP or RF increased the sensitivity to 85%, and when they both were present, the specificity increased to 98%. Among the 39 RA patients, 26 (66.7%) tested positive for RF, and 31 (79.5%) tested positive for anti-CCP. RF was positive in two of eight anti-CCP-negative patients with RA, and anti-CCP was positive in seven of 13 RF-negative patients with RA. CONCLUSIONS: The RF and anti-CCP tests are complementary, and the co-detection of these antibodies can increase the detection rate and provide important clinical value in the diagnosis of RA. Both anti-CCP and RF positivity are useful for the diagnosis of RA, and use of both tests together improves the diagnostic sensitivity.


Assuntos
Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue , Adulto , Idoso , Área Sob a Curva , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Feminino , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taiwan
15.
Elife ; 42015 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-26559620

RESUMO

Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na(+)-dependent K(+) (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations.


Assuntos
Potenciais de Ação , Gânglios Espinais/fisiologia , Técnicas de Inativação de Genes , Proteínas do Tecido Nervoso/deficiência , Neurônios/fisiologia , Canais de Potássio/deficiência , Prurido , Animais , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Dor , Canais de Potássio/metabolismo , Canais de Potássio Ativados por Sódio
16.
Proc Natl Acad Sci U S A ; 112(8): 2599-604, 2015 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-25675513

RESUMO

Following entry into the female reproductive tract, mammalian sperm undergo a maturation process termed capacitation that results in competence to fertilize ova. Associated with capacitation is an increase in membrane conductance to both Ca(2+) and K(+), leading to an elevation in cytosolic Ca(2+) critical for activation of hyperactivated swimming motility. In mice, the Ca(2+) conductance (alkalization-activated Ca(2+)-permeable sperm channel, CATSPER) arises from an ensemble of CATSPER subunits, whereas the K(+) conductance (sperm pH-regulated K(+) current, KSPER) arises from a pore-forming ion channel subunit encoded by the slo3 gene (SLO3) subunit. In the mouse, both CATSPER and KSPER are activated by cytosolic alkalization and a concerted activation of CATSPER and KSPER is likely a common facet of capacitation-associated increases in Ca(2+) and K(+) conductance among various mammalian species. The properties of heterologously expressed mouse SLO3 channels differ from native mouse KSPER current. Recently, a potential KSPER auxiliary subunit, leucine-rich-repeat-containing protein 52 (LRRC52), was identified in mouse sperm and shown to shift gating of SLO3 to be more equivalent to native KSPER. Here, we show that genetic KO of LRRC52 results in mice with severely impaired fertility. Activation of KSPER current in sperm lacking LRRC52 requires more positive voltages and higher pH than for WT KSPER. These results establish a critical role of LRRC52 in KSPER channels and demonstrate that loss of a non-pore-forming auxiliary subunit results in severe fertility impairment. Furthermore, through analysis of several genotypes that influence KSPER current properties we show that in vitro fertilization competence correlates with the net KSPER conductance available for activation under physiological conditions.


Assuntos
Canais de Cálcio/metabolismo , Fertilidade , Ativação do Canal Iônico , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Proteínas de Membrana/metabolismo , Subunidades Proteicas/metabolismo , Espermatozoides/metabolismo , Potenciais de Ação , Álcalis , Animais , Epididimo/fisiologia , Deleção de Genes , Genótipo , Proteínas de Fluorescência Verde/metabolismo , Masculino , Proteínas de Membrana/deficiência , Camundongos Knockout
17.
Stem Cells Dev ; 24(9): 1082-95, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25519920

RESUMO

The differentiation of human pluripotent stem cells to the B-cell lymphoid lineage has important clinical applications that include in vitro modeling of developmental lymphogenesis in health and disease. Here, we first demonstrate the capacity of human induced pluripotent stem cells (hiPSCs) to differentiate into CD144(+)CD73(-)CD43/CD235a(-) cells, characterized as hemogenic endothelium, and show that this population is capable of differentiating to CD10(+)CD19(+) B lymphocytes. We also demonstrate that B lymphocytes generated from hiPSCs are able to undergo full VDJ rearrangement and express surface IgM (sIgM(+)), thus representing an immature B-cell subset. Efficiency of sIgM expression on the hiPSC-derived B lymphocytes (∼ 5% of CD19(+) cells) was comparable with B lymphocytes generated from human umbilical cord blood (UCB) hematopoietic progenitor cells. Importantly, when assessed by global transcriptional profiling, hiPSC-derived B-cells show a very high level of similarity when compared with their UCB-derived counterparts, such that from more than 47,000 different transcripts, only 45 were significantly different (with a criteria adjusted P value P<0.05, log FC >1.5 or 2.8-fold). This represents a unique in vitro model to delineate critical events during lymphogeneisis in development and lymphoid diseases such as acute lymphocytic leukemia.


Assuntos
Linfócitos B/citologia , Células Progenitoras Endoteliais/citologia , Imunoglobulina M/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Linfopoese , Antígenos CD/genética , Antígenos CD/metabolismo , Linfócitos B/metabolismo , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Humanos , Imunoglobulina M/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Transcriptoma , Recombinação V(D)J
18.
J Gen Physiol ; 144(4): 275-95, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25267913

RESUMO

Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four ß2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 α subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of ß2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing ß2 subunits, we generated mice in which the gene encoding ß2 was deleted (ß2 knockout [KO]). Comparison of proteins from wild-type (WT) and ß2 KO mice allowed unambiguous demonstration of the presence of ß2 subunit in various tissues and its coassembly with the Slo1 α subunit. We compared current properties and cell firing properties of WT and ß2 KO CCs in slices and found that ß2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the ß2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from ß2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of ß2 subunits may predispose to burst firing.


Assuntos
Células Cromafins/metabolismo , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/deficiência , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Medula Suprarrenal/metabolismo , Animais , Técnicas In Vitro , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Técnicas de Patch-Clamp , RNA/biossíntese , RNA/genética
19.
Br J Haematol ; 166(3): 435-48, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24837254

RESUMO

Human induced pluripotent stem cells (hiPSCs), like embryonic stem cells, are under intense investigation for novel approaches to model disease and for regenerative therapies. Here, we describe the derivation and characterization of hiPSCs from a variety of sources and show that, irrespective of origin or method of reprogramming, hiPSCs can be differentiated on OP9 stroma towards a multi-lineage haemo-endothelial progenitor that can contribute to CD144(+) endothelium, CD235a(+) erythrocytes (myeloid lineage) and CD19(+) B lymphocytes (lymphoid lineage). Within the erythroblast lineage, we were able to demonstrate by single cell analysis (flow cytometry), that hiPSC-derived erythroblasts express alpha globin as previously described, and that a sub-population of these erythroblasts also express haemoglobin F (HbF), indicative of fetal definitive erythropoiesis. More notably however, we were able to demonstrate that a small sub-fraction of HbF positive erythroblasts co-expressed HbA in a highly heterogeneous manner, but analogous to cord blood-derived erythroblasts when cultured using similar methods. Moreover, the HbA expressing erythroblast population could be greatly enhanced (44·0 ± 6·04%) when a defined serum-free approach was employed to isolate a CD31(+) CD45(+) erythro-myeloid progenitor. These findings demonstrate that hiPSCs may represent a useful alternative to standard sources of erythrocytes (RBCs) for future applications in transfusion medicine.


Assuntos
Eritroblastos/citologia , Eritroblastos/metabolismo , Eritropoese/fisiologia , Expressão Gênica , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Globinas beta/genética , gama-Globinas/genética , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Linhagem da Célula , Variações do Número de Cópias de DNA , Humanos , Imunofenotipagem , Cariotipagem , Globinas beta/metabolismo , gama-Globinas/metabolismo
20.
Clin Rheumatol ; 31(11): 1549-57, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22847245

RESUMO

The aim of this retrospective study was to examine the predictors of discontinuation of anti-tumor necrosis factor (TNF) therapy due to adverse events in Chinese patients with rheumatoid arthritis (RA). Anti-TNF-related adverse events were recorded and analyzed in 217 consecutive patients with RA followed in our institution from 2003 to 2010. Time to discontinuation of anti-TNF-α therapy was estimated using survival analysis techniques. The anti-TNF agents administered were etanercept in 181 patients and adalimumab in 36 patients. The mean age at diagnosis was 45.2 ± 13.5 years, and mean age at initiation of anti-TNF therapy was 51.8 ± 13.0 years. The mean duration of anti-TNF agent use was 36.0 ± 26.5 months (range, 1.4-87.0; median, 26.4 months). Of the 217 patients, 39 (18.0 %) developed adverse events [etanercept in 34 (18.8 %] and adalimumab in 5 (13.9 %)] during the treatment period (tuberculosis in 5, bacterial infections in 19, virus infection in 7, neuropathy in 3, malignancy in 3, other drug-related events in 1, and appendicitis in 1). In patients with RA, older age (≥55 years) at initiation of anti-TNF therapy [odds ratio (OR), 3.20; 95 % confidence interval (CI), 1.67-6.20; p < 0.001], Cr ≥1.5 mg/dL (OR, 5.72; 95 % CI, 1.17-27.90; p = 0.031), and occurrence of adverse events (OR, 3.82; 95 % CI, 1.75-8.35; p = 0.001) were associated with increased likelihood of discontinuation of anti-TNF treatment. In the present study, a significant proportion (7.8 %, 17/217) of patients with RA discontinued anti-TNF treatment because of adverse events. In the elderly and in patients with renal insufficiency, caution is needed when starting anti-TNF treatment.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Imunoglobulina G/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adolescente , Adulto , Idoso , Estudos de Coortes , Etanercepte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Receptores do Fator de Necrose Tumoral , Estudos Retrospectivos , Reumatologia/métodos , Taiwan , Fatores de Tempo , Resultado do Tratamento
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