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1.
Chem Soc Rev ; 53(4): 2056-2098, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38214051

RESUMEN

Global warming has become a growing concern over decades, prompting numerous research endeavours to reduce the carbon dioxide (CO2) emission, the major greenhouse gas (GHG). However, the contribution of other non-CO2 GHGs including methane (CH4), nitrous oxide (N2O), fluorocarbons, perfluorinated gases, etc. should not be overlooked, due to their high global warming potential and environmental hazards. In order to reduce the emission of non-CO2 GHGs, advanced separation technologies with high efficiency and low energy consumption such as adsorptive separation or membrane separation are highly desirable. Advanced porous materials (APMs) including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), porous organic polymers (POPs), etc. have been developed to boost the adsorptive and membrane separation, due to their tunable pore structure and surface functionality. This review summarizes the progress of APM adsorbents and membranes for non-CO2 GHG separation. The material design and fabrication strategies, along with the molecular-level separation mechanisms are discussed. Besides, the state-of-the-art separation performance and challenges of various APM materials towards each type of non-CO2 GHG are analyzed, offering insightful guidance for future research. Moreover, practical industrial challenges and opportunities from the aspect of engineering are also discussed, to facilitate the industrial implementation of APMs for non-CO2 GHG separation.

2.
J Am Chem Soc ; 146(28): 19303-19309, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38970779

RESUMEN

Sulfur hexafluoride (SF6) is extensively employed in the power industry. However, its emissions significantly contribute to the greenhouse effect. The direct recovery of high purity SF6 from industrial waste gases would benefit its sustainable use, yet this represents a considerable challenge. Herein, we report the enrichment of SF6 from SF6/N2 mixtures via adsorptive separation in a stable Co(II)-pyrazolate MOF BUT-53 (BUT: Beijing University of Technology), which features dynamic molecular traps. BUT-53 exhibits an excellent SF6 adsorption uptake of 2.82 mmol/g at 0.1 bar and 298 K, as well as an unprecedented SF6/N2 (10:90) selectivity of 2485. Besides, the remarkable SF6/N2 selectivity of BUT-53 enables recovery of high purity (>99.9%) SF6 from a low concentration (10%) mixture through a breakthrough experiment. The excellent SF6/N2 separation efficiency was also well maintained under humid conditions (RH = 90%) over multiple cycles. Molecular simulation, single-crystal diffraction, and adsorption kinetics studies elucidate the associated adsorption mechanism and water tolerance.

3.
Small ; 20(25): e2307281, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38225701

RESUMEN

Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti-inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA-DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA-DCF) as the MNs tips and then modifying the surface of MNs tips with a self-adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti-inflammatory cell tests and therapeutic animal experiments, down-regulating the expression levels of pro-inflammatory factors and alleviating articular cartilage destruction.


Asunto(s)
Diclofenaco , Sistemas de Liberación de Medicamentos , Ácido Hialurónico , Agujas , Osteoartritis , Osteoartritis/tratamiento farmacológico , Animales , Diclofenaco/administración & dosificación , Diclofenaco/uso terapéutico , Diclofenaco/farmacología , Ácido Hialurónico/química , Lubrificación , Humanos , Preparaciones de Acción Retardada/química
4.
Cytometry A ; 105(6): 437-445, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38549391

RESUMEN

Circulating inflammatory cells in eyes have emerged as early indicators of numerous major diseases, yet the monitoring of these cells remains an underdeveloped field. In vivo flow cytometry (IVFC), a noninvasive technique, offers the promise of real-time, dynamic quantification of circulating cells. However, IVFC has not seen extensive applications in the detection of circulating cells in eyes, possibly due to the eye's unique physiological structure and fundus imaging limitations. This study reviews the current research progress in retinal flow cytometry and other fundus examination techniques, such as adaptive optics, ultra-widefield retinal imaging, multispectral imaging, and optical coherence tomography, to propose novel ideas for circulating cell monitoring.


Asunto(s)
Citometría de Flujo , Tomografía de Coherencia Óptica , Citometría de Flujo/métodos , Humanos , Tomografía de Coherencia Óptica/métodos , Retina/citología , Retina/diagnóstico por imagen , Ojo , Animales
5.
Artículo en Inglés | MEDLINE | ID: mdl-38969612

RESUMEN

With advancements in extracorporeal life support (ECLS) technologies, venoarterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a crucial cardiopulmonary support mechanism. This review explores the significance of VA-ECMO system configuration, cannulation strategies, and timing of initiation. Through an analysis of medication management strategies, complication management, and comprehensive preweaning assessments, it aims to establish a multidimensional evaluation framework to assist clinicians in making informed decisions regarding weaning from VA-ECMO, thereby ensuring the safe and effective transition of patients.

6.
Nano Lett ; 23(2): 523-532, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36622363

RESUMEN

Ultralong carbon nanotubes (CNTs) are in huge demand in many cutting-edge fields due to their macroscale lengths, perfect structures, and extraordinary properties, while their practical application is limited by the difficulties in their mass production. Herein, we report the synthesis of ultralong CNTs with a dramatically increased yield by a simple but efficient substrate interception and direction strategy (SIDS), which couples the advantages of floating-catalyst chemical vapor deposition with the flying-kite-like growth mechanism of ultralong CNTs. The SIDS-assisted approach prominently improves the catalyst utilization and significantly increases the yield. The areal density of the ultralong CNT arrays with length of over 1 cm reached a record-breaking value of ∼6700 CNTs mm-1, which is 2-3 orders of magnitude higher than the previously reported values obtained by traditional methods. The SIDS provides a solution for synthesizing high-quality ultralong CNTs with high yields, laying the foundation for their mass production.

7.
Pharm Biol ; 62(1): 423-435, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38757785

RESUMEN

CONTEXT: Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota. OBJECTIVE: This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation. METHODS: We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD. RESULTS: Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD. CONCLUSION: This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.


Asunto(s)
Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Medicina Tradicional China , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Humanos , Nefropatías Diabéticas/tratamiento farmacológico , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Animales
8.
Angew Chem Int Ed Engl ; : e202411744, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012658

RESUMEN

Adsorptive C2H2/C2H4 separation using metal-organic frameworks (MOFs) has emerged as a promising technology for the removal of C2H2 (acetylene) impurity (1%) from C2H4 (ethylene). The practical application of these materials involves the optimization of separation performance as well as development of scalable and green production protocols.Herein, we report the efficient C2H2/C2H4 separation in a MOF, Cu(OH)INA (INA: isonicotinate) which achieves a record C2H2 packing density of 351 mg cm-3 at 0.01 bar through high affinity towards C2H2. DFT (density functional theory) calculations reveal the synergistic binding mechanism through pore confinement and the oxygen sites in pore wall.The weakly basic nature of binding sites leads to a relatively low heat of adsorption (Qst) of approximately 36 kJ/mol, which is beneficial for material regeneration and thermal management. Furthermore, a scalable and environmentally friendly synthesis protocol with a high space-time yield of 544 kg m-3 day-1 has been developed without using any modulating agents. This material also demonstrates enduring separation performance for multiple cycles, maintaining its efficacy after exposure to water or air for three months.

9.
Langmuir ; 38(49): 15178-15189, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36468673

RESUMEN

The lubrication property of implanted biomedical devices is of great significance as it affects the clinical performance owing to direct contact with soft tissues. In the present study, a bioinspired copolymer with dual functions of both self-adhesion and lubrication was synthesized with N-(3-aminopropyl) methacrylamide hydrochloride, gallic acid, and 3-[dimethyl-[2-(2-methylprop-2-enoyloxy) ethyl] azaniumyl] propane-1-sulfonate by free radical polymerization and a carbodiimide coupling reaction. The copolymer was further modified on the surface of poly(vinyl chloride) (PVC) samples using a simple dip-coating method and was characterized by different evaluations including Fourier transform infrared spectroscopy, the water contact angle, X-ray photoelectron spectroscopy, optical interferometry, and atomic force microscopy. Additionally, the results of a series of tribological tests at the microscopic level demonstrated that the friction coefficient of the copolymer-coated PVC samples was significantly reduced compared to that of the bare PVC samples. Furthermore, the pull out test at the macroscopic level was performed using copolymer-coated PVC catheters on a poly(dimethylsiloxane)-based test rig, and the result showed that the copolymer-coated PVC catheters were endowed with a greatly decreased and much more stable pull out force compared with that of the bare PVC catheters. In conclusion, the bioinspired self-adhesive lubricated coating developed herein may be applied as a universal and versatile method to enhance the lubrication performance of implanted biomedical devices.


Asunto(s)
Adhesivos , Cementos de Resina , Polimerizacion , Polímeros/química , Microscopía de Fuerza Atómica , Propiedades de Superficie
10.
Langmuir ; 38(18): 5924-5933, 2022 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-35446583

RESUMEN

In orthopedics, developing functionalized biomaterials to enhance osteogenesis and bacterial resistance is crucial. Although poly(ether ether ketone) (PEEK) is regarded as an important engineering plastic for biomedical material with excellent mechanical properties and biocompatibility, its biological inertness has greatly compromised its application in biomedical engineering. Inspired by the catecholamine chemistry of mussels, we propose a universal and versatile approach for enhancing the osteogenesis and antibacterial performances of PEEK based on surface functionalization of polydopamine-modified nanohydroxyapatite and lysozyme simultaneously. The characterizations of surface morphology and elemental composition revealed that the composite coating was successfully added to the PEEK surface. Additionally, the in vitro cell experiment and biomineralization assay indicated that the composite coating-modified PEEK was biocompatible with significantly improved bioactivity to promote osteogenesis and biomineralization compared with the untreated PEEK. Furthermore, the antibacterial test demonstrated that the composite coating had a strongly destructive effect on two bacteria (Staphylococcus aureus and Escherichia coli) with antibacterial ratios of 98.7% and 96.1%, respectively. In summary, the bioinspired method for surface functionalization can enhance the osteogenesis and bacterial resistance of biomedical materials, which may represent a potential approach for designing functionalized implants in orthopedics.


Asunto(s)
Cetonas , Osteogénesis , Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Éter/farmacología , Éteres/farmacología , Cetonas/farmacología , Polietilenglicoles/farmacología , Propiedades de Superficie
11.
Entropy (Basel) ; 24(1)2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35052155

RESUMEN

Cognitive radio, as a key technology to improve the utilization of radio spectrum, acquired much attention. Moreover, spectrum sensing has an irreplaceable position in the field of cognitive radio and was widely studied. The convolutional neural networks (CNNs) and the gate recurrent unit (GRU) are complementary in their modelling capabilities. In this paper, we introduce a CNN-GRU network to obtain the local information for single-node spectrum sensing, in which CNN is used to extract spatial feature and GRU is used to extract the temporal feature. Then, the combination network receives the features extracted by the CNN-GRU network to achieve multifeatures combination and obtains the final cooperation result. The cooperative spectrum sensing scheme based on Multifeatures Combination Network enhances the sensing reliability by fusing the local information from different sensing nodes. To accommodate the detection of multiple types of signals, we generated 8 kinds of modulation types to train the model. Theoretical analysis and simulation results show that the cooperative spectrum sensing algorithm proposed in this paper improved detection performance with no prior knowledge about the information of primary user or channel state. Our proposed method achieved competitive performance under the condition of large dynamic signal-to-noise ratio.

12.
Opt Express ; 28(24): 36176-36187, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33379718

RESUMEN

Accurate overlapping-peaks extraction plays a critical role in chromatic confocal thickness measurement of ultra-thin transparent film. However, the current algorithms usually appear as a perceptible extraction error resulting from the disturbing influence among peaks in the process of fitting the spectral axial response signal (sARS) of the two measuring surfaces. In this paper, we propose an adaptive modal decomposition method to extract multi peaks for the ultra-thin materials. With this method, the sARS can be firstly decomposed into several sub-modes, which can be used to obtain the peak wavelength of each measuring surface by the existing single peak extraction algorithms, such as the centroid method and Gauss fitting method. Monte Carlo simulations and experimental tests demonstrate that the proposed algorithm has significant improvements over the existing nonlinear fitting algorithms in terms of peak extraction accuracy and precision.

13.
Nat Chem Biol ; 13(9): 994-1001, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28759015

RESUMEN

The binding of adenomatous polyposis coli (APC) to its receptor Asef relieves the negative intramolecular regulation of Asef and leads to aberrant cell migration in human colorectal cancer. Because of its crucial role in metastatic dissemination, the interaction between APC and Asef is an attractive target for anti-colorectal-cancer therapy. We rationally designed a series of peptidomimetics that act as potent inhibitors of the APC interface. Crystal structures and biochemical and cellular assays showed that the peptidomimetics in the APC pocket inhibited the migration of colorectal cells by disrupting APC-Asef interaction. By using the peptidomimetic inhibitor as a chemical probe, we found that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation in colorectal cancer cells. Our work demonstrates the feasibility of exploiting APC-Asef interaction to regulate the migration of colorectal cancer cells, and provides what to our knowledge is the first class of protein-protein interaction inhibitors available for the development of cancer therapeutics targeting APC-Asef signaling.


Asunto(s)
Poliposis Adenomatosa del Colon/metabolismo , Neoplasias Colorrectales , Oligopéptidos/química , Péptidos/farmacología , Peptidomiméticos , Poliposis Adenomatosa del Colon/química , Unión Competitiva , Movimiento Celular , Neoplasias Colorrectales/fisiopatología , Humanos , Oligopéptidos/farmacología , Péptidos/química , Unión Proteica/efectos de los fármacos , Factores de Intercambio de Guanina Nucleótido Rho/química , Factores de Intercambio de Guanina Nucleótido Rho/efectos de los fármacos , Factores de Intercambio de Guanina Nucleótido Rho/metabolismo
14.
Acta Pharmacol Sin ; 40(4): 563-568, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29941870

RESUMEN

The chemokine receptor CCR5 is an important anti-HIV (human immunodeficiency virus) drug target owning to its pivotal role in HIV-1 viral entry as a co-receptor. Here, we present a 2.9 Å resolution crystal structure of CCR5 bound to PF-232798, a second-generation oral CCR5 antagonist currently in phase II clinical trials. PF-232798 and the marketed HIV drug maraviroc share a similar tropane scaffold with different amino (N)- and carboxyl (C)- substituents. Comparison of the CCR5-PF-232798 structure with the previously determined structure of CCR5 in complex with maraviroc reveals different binding modes of the two allosteric antagonists and subsequent conformational changes of the receptor. Our results not only offer insights into the phenomenon that PF-232798 has higher affinity and alternative resistance profile to maraviroc, but also will facilitate the design of new anti-HIV drugs.


Asunto(s)
Fármacos Anti-VIH/farmacología , Compuestos de Azabiciclo/farmacología , Imidazoles/farmacología , Receptores CCR5/metabolismo , Fármacos Anti-VIH/química , Compuestos de Azabiciclo/química , Sitios de Unión/efectos de los fármacos , Cristalografía por Rayos X , Humanos , Imidazoles/química , Modelos Moleculares , Receptores CCR5/química , Tropanos
15.
J Neuroinflammation ; 15(1): 167, 2018 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-29807548

RESUMEN

BACKGROUND: Remote ischemic preconditioning (RIPC) of a limb has been reported to protect against ischemic stroke. Our previous results demonstrated that the RIPC-mediated neuroprotection is associated with alterations in circulating immune cell populations. Here, we evaluated the effect of the spleen, the largest reservoir of immune cells, on RIPC-mediated neuroprotection against stroke. METHODS: Noninvasive RIPC was achieved by four repeated cycles of 5-min blood flow constriction in the hindlimbs using a tourniquet. The blood and spleens were collected before and 1 h and 3 days after preconditioning to analyze the effect of RIPC on the spleen and the correlation between splenic and peripheral lymphocytes. Moreover, spleen weight and splenic lymphocytes were compared in stroke rats with or without RIPC. Finally, splenectomy was made 1 day or 2 weeks before RIPC and 90-min middle cerebral artery occlusion (MCAO). The infarct areas and deficits were assessed. Blood was collected 1 h after RIPC and 3 days after MCAO to explore the impact of splenectomy on RIPC-induced neuroprotection and immune changes. The contralateral and ipsilateral hemispheres were collected 3 days after MCAO to detect the infiltration of immune cells after RIPC and splenectomy. RESULTS: Flow cytometry analysis demonstrated that the RIPC promptly increased the percentages of CD3+CD8+ cytotoxic T (Tc) cells in the spleen with a relatively delayed elevation in CD3+CD161+ natural killer T (NKT) and CD3-CD45RA+ B lymphocytes. The percentages of circulating lymphocytes are positively correlated with the percentages of splenic lymphocytes in normal rats. Interestingly, RIPC resulted in negative correlations between the percentages of splenic and circulating T lymphocytes, while the correlation between splenic and circulating B lymphocytes remained positive. For animals subjected to RIPC followed by MCAO, RIPC increased splenic volume with an expansion of splenic lymphocytes 3 days after MCAO. Furthermore, the removal of the spleen 1 day or 2 weeks before RIPC and MCAO reduced the protective effect of RIPC on ischemic brain injury and reversed the effects of RIPC on circulating immune cell composition. RIPC significantly reduced brain infiltration of Tc and NKT cells. Prior splenectomy showed no effect on immune cell infiltration after RIPC and stroke. CONCLUSION: These results reveal an immunomodulatory effect of the spleen, effecting mainly the spleen-derived lymphocytes, during RIPC-afforded neuroprotection against cerebral ischemia.


Asunto(s)
Miembro Posterior/fisiología , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/terapia , Precondicionamiento Isquémico/métodos , Bazo/fisiopatología , Animales , Antígenos CD/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/complicaciones , Leucocitos/metabolismo , Masculino , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/prevención & control , Equilibrio Postural , Ratas , Ratas Sprague-Dawley , Reperfusión , Bazo/patología , Esplenectomía , Factores de Tiempo
16.
Biotechnol Lett ; 38(5): 835-40, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26906344

RESUMEN

OBJECTIVES: To develop a sensitive and specific molecular assay for detection of mango malformation disease (MMD), which is caused primarily by Fusarium mangiferae. RESULTS: We screened 100 ISSR primers and identified one (UBC888) that directed the stable amplification of a specific gene fragment of 479 bp (GenBank accession number KJ526382). Based on the DNA sequence of this fragment, a pair of SCAR primers (W342 and W1772) were designed to amplify another gene fragment of 1376 bp (GenBank accession number KJ526383), demonstrating the successful conversion of an ISSR marker to a SCAR marker. An effective and simple detection assay for MMD was established based on this pair of PCR primers, with a high level of specificity and sensitivity to the DNA of F. mangiferae and other species of Fusarium both in vitro and in vivo. It can detect as little as 10 pg fungal DNA from the DNA of mango's tissues. CONCLUSIONS: Our assay provides a practical method for the early diagnosis so that proper prevention of the mango malformation disease can be developed.


Asunto(s)
Fusarium/aislamiento & purificación , Mangifera/microbiología , Enfermedades de las Plantas/microbiología , Reacción en Cadena de la Polimerasa/métodos , Cartilla de ADN/genética , Fusarium/genética , Sensibilidad y Especificidad
17.
Acta Biochim Biophys Sin (Shanghai) ; 48(8): 714-22, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27353320

RESUMEN

Ischemia/reperfusion injury (IRI) is a major cause of acute kidney damage, which often occurs in deceased donor kidney transplants. Cathelicidin PR-39 peptide possesses anti-inflammatory and wound repair effects through tissue angiogenesis and anti-apoptosis. This study assessed the role of PR-39 in anti-apoptosis in vitro using a lentiviral vector with a kidney specific promoter (KSP) to drive PR-39 expression. Our data revealed that PR-39 peptide was specifically over-expressed in kidney-derived HK-2 cells, but was scarcely detected in non-kidney tissue-derived cells. PR-39 over-expression had a protective role in the hypoxia/re-oxygenation (H/R) treated cells. The anti-apoptotic activity of PR-39 peptide was mediated by the inhibition of caspase-2, caspase-12 and caspase-3 activity in the endoplasmic reticulum (ER) stress-induced apoptotic pathway. It was also revealed that the anti-apoptotic effect of PR-39 peptide was mediated by an apoptosis-related protein, cellular inhibitor apoptosis protein-2 (c-IAP-2). Taken together, the current data demonstrate that PR-39 expression driven by KSP could prevent kidney damage (apoptosis) from IRI via the ER stress-induced apoptotic pathway.


Asunto(s)
Apoptosis/efectos de los fármacos , Catelicidinas/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hipoxia/prevención & control , Daño por Reperfusión/prevención & control , Animales , Citometría de Flujo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Riñón/patología , Ratones , Células 3T3 NIH , Daño por Reperfusión/patología
18.
Ann Hum Genet ; 79(4): 294-309, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25959545

RESUMEN

In genetic association studies of an ordered categorical phenotype, it is usual to either regroup multiple categories of the phenotype into two categories and then apply the logistic regression (LG), or apply ordered logistic (oLG), or ordered probit (oPRB) regression, which accounts for the ordinal nature of the phenotype. However, they may lose statistical power or may not control type I error due to their model assumption and/or instable parameter estimation algorithm when the genetic variant is rare or sample size is limited. To solve this problem, we propose a set-valued (SV) system model to identify genetic variants associated with an ordinal categorical phenotype. We couple this model with a SV system identification algorithm to identify all the key system parameters. Simulations and two real data analyses show that SV and LG accurately controlled the Type I error rate even at a significance level of 10(-6) but not oLG and oPRB in some cases. LG had significantly less power than the other three methods due to disregarding of the ordinal nature of the phenotype, and SV had similar or greater power than oLG and oPRB. We argue that SV should be employed in genetic association studies for ordered categorical phenotype.


Asunto(s)
Algoritmos , Estudios de Asociación Genética , Modelos Genéticos , Simulación por Computador , Humanos , Modelos Logísticos , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
19.
Hum Hered ; 78(2): 104-16, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25096228

RESUMEN

We propose in this paper a set-valued (SV) system model, which is a generalized form of logistic (LG) and Probit (Probit) regression, to be considered as a method for discovering genetic variants, especially rare genetic variants in next-generation sequencing studies, for a binary phenotype. We propose a new SV system identification method to estimate all underlying key system parameters for the Probit model and compare it with the LG model in the setting of genetic association studies. Across an extensive series of simulation studies, the Probit method maintained type I error control and had similar or greater power than the LG method, which is robust to different distributions of noise: logistic, normal, or t distributions. Additionally, the Probit association parameter estimate was 2.7-46.8-fold less variable than the LG log-odds ratio association parameter estimate. Less variability in the association parameter estimate translates to greater power and robustness across the spectrum of minor allele frequencies (MAFs), and these advantages are the most pronounced for rare variants. For instance, in a simulation that generated data from an additive logistic model with an odds ratio of 7.4 for a rare single nucleotide polymorphism with a MAF of 0.005 and a sample size of 2,300, the Probit method had 60% power whereas the LG method had 25% power at the α = 10(-6) level. Consistent with these simulation results, the set of variants identified by the LG method was a subset of those identified by the Probit method in two example analyses. Thus, we suggest the Probit method may be a competitive alternative to the LG method in genetic association studies such as candidate gene, genome-wide, or next-generation sequencing studies for a binary phenotype.


Asunto(s)
Estudios de Asociación Genética/estadística & datos numéricos , Variación Genética , Modelos Estadísticos , Análisis de Regresión , Simulación por Computador , Proteínas de Unión al ADN/genética , Exoma , Humanos , Fenotipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Factores de Transcripción/genética
20.
Bioinformatics ; 29(18): 2357-9, 2013 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-23842804

RESUMEN

MOTIVATION: The use of allosteric modulators as preferred therapeutic agents against classic orthosteric ligands has colossal advantages, including higher specificity, fewer side effects and lower toxicity. Therefore, the computational prediction of allosteric sites in proteins is receiving increased attention in the field of drug discovery. Allosite is a newly developed automatic tool for the prediction of allosteric sites in proteins of interest and is now available through a web server. AVAILABILITY: The Allosite server and tutorials are freely available at http://mdl.shsmu.edu.cn/AST CONTACT: jian.zhang@sjtu.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Proteínas/química , Programas Informáticos , Algoritmos , Sitio Alostérico , Descubrimiento de Drogas , Ligandos , Proteínas/metabolismo
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