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1.
Drug Deliv ; 27(1): 161-169, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31913730

RESUMO

Bone-metastasis prostate cancer (BMPCa)-targeting gene therapy is gaining increasing concern in recent years. The peptide T7-modified polypeptide nanoparticles for delivery DNA (CRD-PEG-T7/pPMEPA1) was prepared as our previous study. However, the feasibility of CRD-PEG-T7/pPMEPA1 for BMPCa treatment, the mechanisms underlying cellular uptake, anti-BMPCa effect, and administration safety requires further research. LNCaP cells treated with endocytosis inhibitors and excessive T7 under different culture condition were carried out to investigate the mechanisms of cellular uptake of the CRD-PEG-T7-pPMEPA1. A transwell assay was applied to evaluate the cell migration ability. Besides, the tumor volume and survival rates of the PCa xenograft mice model were recorded to estimate the anti-tumor effect. In addition, the weight profiles of the PCa tumor-bearing mice, the blood chemistry, and the HE analysis of visceral organs and tumor was conducted to investigate the administration safety of CRD-PEG-T7/pPMEPA1. The results showed that PCa cellular uptake was decreased after treating with excessive free T7, endocytosis inhibitors and lower incubation temperature. Besides, CRD-PEG-T7/pPMEPA1 could inhibit the LNCaP cells chemotaxis and tumor growth. In addition, the survival duration of the PCa tumor-bearing mice treating with CRD-PEG-T7/pPMEPA1 was significantly prolonged with any systemic toxicity or damage to the organs. In conclusion, this research proposes a promising stratagem for treatment BMPCa by providing the biocompatible and effective carrier for delivery DNA therapeutic agents.

2.
J Biomol Struct Dyn ; : 1-9, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31872783

RESUMO

Src homology 3 (SH3) domains are small protein modules involved in the regulation of important cellular pathways such as proliferation and migration, which canonically prefer to recognize and interact with proline-rich peptide ligands with class I or class II motif. Previously, we identified two self-binding peptides (SBPs) in human c-Src tyrosine kinase, of which the first SBP (fSBP) segment (248SKPQTQGLAK257) fulfills intramolecular interaction with the kinase SH3 domain to regulate the kinase function. The segment (and its equivalents in other c-Src family members) does not contain canonical class II motif (PxxQxL versus PxxPx+), but can bind to SH3 domain in a routine class II mode. Existing theories such as non-polyproline-II binding conformation, unusual peptide-binding pocket and extensive use of contacts cannot explain this atypical recognition phenomenon. Here, we performed a systematic investigation of SH3-fSBP binding in different conditions, including the segment in full-length kinase or in isolated state, the kinase in different forms and the fSBP residue mutations, by using microsecond molecular dynamics simulations, conformational clustering analyses and binding energetics calculations. We purposed a new mechanism that the protein context is primarily responsible for the atypical intramolecular SH3-fSBP recognition in c-Src kinase, which can promote the tight packing of segment against domain surface, support the segment polyproline-II (PPII) conformation in unbound state, and avoid unfavorable segment interactions with SH3 charged region by forming a C-terminal t-turn. In addition, the only proline residue Pro250 of fSBP segment is also required for the segment recognition by SH3 domain in c-Src kinase context; lack of Pro250 residue the segment exhibits considerable disorder and cannot maintain in PPII helical conformation, thus largely impairing the domain-segment binding capability. Further binding analysis confirms that the isolated fSBP peptide cannot bind effectively to SH3 domain out of kinase context, whereas its mutant version, i.e. fSBP(Q253P/L255R) peptide, which possesses the canonical class II motif, exhibits an increased affinity to the domain.Communicated by Ramaswamy H. Sarma.

3.
J Hazard Mater ; 380: 120904, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31336270

RESUMO

A hierarchical porous composite of Pt@MIL-101/ployvinylidene fluoride (Pt@MIL-101/PVDF) was successfully prepared through a solution-processed method. This composite possesses advanced superhydrophobic and superaerophilic performance which makes it a promising catalyst facilitating liquid phase catalytic exchange techniques (LPCE) in hydrogen-water isotope exchange process. Its superhydrophobic property results in the repellence of water drops from flooding the catalytic surface with a relatively large contact angle in the exchange reaction, and its superaerophilic surface broke hydrogen bubbles into thin film so as to reach higher catalytic reactive efficiency. High reactivity and long-term stability in the reaction process can also be achieved by the configuration of mesoporous cages of MIL-101 confining Pt nanoparticles and preventing them from sintering.

4.
Micromachines (Basel) ; 10(6)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31248148

RESUMO

The single-cell capture microfluidic chip has many advantages, including low cost, high throughput, easy manufacturing, integration, non-toxicity and good stability. Because of these characteristics, the cell capture microfluidic chip is increasingly becoming an important carrier on the study of life science and pharmaceutical analysis. Important promises of single-cell analysis are the paring, fusion, disruption and analysis of intracellular components for capturing a single cell. The capture, which is based on the fluid dynamics method in the field of micro fluidic chips is an important way to achieve and realize the operations mentioned above. The aim of this study was to compare the ability of three fluid dynamics-based microfluidic chip structures to capture cells. The effects of cell growth and distribution after being captured by different structural chips and the subsequent observation and analysis of single cells on the chip were compared. It can be seen from the experimental results that the microfluidic chip structure most suitable for single-cell capture is a U-shaped structure. It enables single-cell capture as well as long-term continuous culture and the single-cell observation of captured cells. Compared to the U-shaped structure, the cells captured by the microcavity structure easily overlapped during the culture process and affected the subsequent analysis of single cells. The flow shortcut structure can also be used to capture and observe single cells, however, the shearing force of the fluid caused by the chip structure is likely to cause deformation of the cultured cells. By comparing the cell capture efficiency of the three chips, the reagent loss during the culture process and the cell growth state of the captured cells, we are provided with a theoretical support for the design of a single-cell capture microfluidic chip and a reference for the study of single-cell capture in the future.

5.
ACS Appl Mater Interfaces ; 11(6): 6396-6403, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30652848

RESUMO

Triboelectric nanogenerators (TENGs) have been investigated for mechanical energy harvesting because of their high-energy conversion efficiency, low cost, ease of manufacturing, and so on. This paper deals with designing a kind of water-fluid-driven rotating TENG (WR-TENG) inspired by the structure of a water meter. The designed WR-TENG is effectively integrated into a self-powered electrostatic scale-preventing and rust protection system. The WR-TENG can generate a constant DC voltage up to about 7.6 kV by using a voltage-doubling rectifier circuit (VDRC) to establish a high-voltage electrostatic field in the water tank. A WR-TENG, a VDRC, and an electric water heating tank are the components of the whole system. The system is convenient to be installed in any waterway system, effectively preventing the rusting of stainless steel and restraining the formation of scale when the water is heated to 65 ± 5 °C. Moreover, the approximately linear relationship between the short-circuit current and the rotation rate of the WR-TENG makes employing it as a self-powered water flow sensor possible. This work enables a facile, safe, and effective approach for electrostatic scale prevention, rust protection, and flow sensing in solar heaters, which will enrich the high-voltage applications of TENGs.

6.
Nanoscale ; 10(30): 14747-14754, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30043011

RESUMO

With the rapid development of portable electronics, exploring sustainable power sources is becoming more and more urgent. Utilizing a nanogenerator to harvest ambient mechanical energy could be an effective approach to solve this challenge. In this work, a novel spring-assisted hybrid nanogenerator (HG) consisting of a triboelectric nanogenerator (TENG) and an electromagnetic generator (EMG) was developed for harvesting low-frequency vibration energy. The results show that the TENG with a PTFE surface nanostructure has better output performance than that without the nanostructure. The effect of operating frequency on the open-circuit voltage and short-circuit current of the TENG and EMG is systematically investigated. Under a 2 Hz operating frequency, the EMG and TENG are able to produce a peak power of about 57.6 mW with a resistive load of 2000 Ω and 1682 µW with a resistive load of 50 MΩ, respectively. The impedance matching between the TENG and EMG can be realized by using a transformer to reduce the impedance of the TENG. The charging performance of the HG is much better than that of the individual EMG or TENG. The HG enabled us to develop a self-powered safety system and to power LEDs, and drive some electronic devices. The present work provides a superior solution to improve the output performance of the HG for harvesting low-frequency vibration energy.

7.
Artif Cells Nanomed Biotechnol ; 46(6): 1122-1131, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28754059

RESUMO

Proto-oncogene non-receptor tyrosine protein kinase c-Src has been involved in the development, progression and metastasis of a variety of human cancers. This protein contains two self-binding peptide (SBP) sites separately between the SH3 domain and polyproline-II (PPII) helix and between the SH2 domain and C-terminal phosphorylatable tail (CTPT), which are potential targets of anticancer drugs to regulate the kinase activity. Here, we described an integrated protocol to systematically investigate the structural basis, energetic property and dynamics behaviour of PPII binding to SH3, and to rationally design potent peptide ligands to target the SBP site of SH3-PPII interaction. Our study found that the PPII peptide is a non-typical binder that can only interact effectively with its cognate SH3 domain when it is integrated into the full-length c-Src kinase protein; stripping the peptide from the protein would considerably impair SH3 affinity by increasing entropy penalty upon the domain-peptide binding, suggesting that the protein context plays an essential role in the SBP's biological function. Next, we identified that the PPII peptide binds to SH3 domain in a class II manner and, on this basis, we derived a series of modified versions of the wild-type PPII peptide using a structure-based rational strategy. These modified peptide mutants have been structurally optimized with respect to their molecular flexibility and interaction potency with SH3 domain, in order to minimize indirect entropy penalty and to maximize direct binding enthalpy simultaneously. Consequently, several rationally designed peptides were obtained, including PPIIm2 (TSKPQTPGRA), PPIIm5 (KPPTPPRA), PPIIm6 (FPPPPPRA) and PPIIm7 (YPPLPPRA), which exhibit a moderately or considerably increased affinity (Kd = 72, 34, 15 and 5.7 µM, respectively) relative to the wild-type PPII (TSKPQTQGLA) (Kd = 160 µM). These peptides can be used as lead molecular entities to further develop new anticancer therapeutics to regulate c-Src kinase activity by targeting the SBP site of SH3-PPII interaction.


Assuntos
Peptídeos/química , Peptídeos/metabolismo , Domínios de Homologia de src , Quinases da Família src/química , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Humanos , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade , Termodinâmica , Quinases da Família src/metabolismo
8.
Se Pu ; 35(10): 1023-1027, 2017 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-29048797

RESUMO

CPL-1 is a metal organic framework (MOF) with potential application as stationary phase material in gas chromatographic (GC) analysis, due to its large specific surface area, uniform pore size and good quantum sieving effect on hydrogen isotopes at low temperatures. Herein, a microporous column packed with CPL-1 was used at cryogenic temperature (77 K), and the column was 1.0 mm in inner diameter, 0.5 m in length. Single crystals of Al2O3 was used to build flow path for chromatographic carrier gas. The results showed that the adsorption of H2 and D2 with CPL-1 was 4 mmol/g at 77 K, which was better than MnCl2/γ -Al2O3 and γ -Al2O3. With the injection volume increasing from 0.25 mL to 2 mL, the results showed good linear relationship, and the relative error was less than 4%. The results indicated that the column packed with CPL-1 has wide linear range, good repeatability and high accuracy, and it has potential use in hydrogen isotope analysis with gas chromatography.

9.
Se Pu ; 35(7): 766-771, 2017 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-29048843

RESUMO

The conventional packed column gas chromatographic analysis of hydrogen isotopes has low column efficiency, broad peak and long retention time. In this work, a γ-Al2O3 with MnCl2 coated capillary packed column was tested at cryogenic temperature. The systematic column efficiency analysis and the hydrogen isotopes analytical technique research had been carried out. The results showed that, the γ-Al2O3 with MnCl2 coating could greatly improve the surface degree of order, pore structure and adsorption properties. Also the o-H2 peak and p-H2 peak were eluted in a single area. The γ-Al2O3 with MnCl2 coating was packed into a 0.53 mm inner diameter and 1.0 m long fused silica capillary column. It had a good linear relationship used this column with thermal conductivity detector (TCD) to detect the volume concentrations of hydrogen isotopes from 1 to 10 mL/L, and the relative error was less than 5% for low concentration sample testing. For H2, HD and D2, the retention times can be shortened to 39, 46 and 60 s, respectively. The limits of detection were reduced to 0.046, 0.067 and 0.072 mL/L, respectively. Compared with conventional packed column, capillary packed column had sharper peak form, higher separation degree of adjacent components, shorter retention time and lower detection limits. The above results indicate that the capillary packed column with TCD detector can be used for fast detection of low concentration of hydrogen isotopes and their online analysis.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(4): 430-435, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28407831

RESUMO

OBJECTIVE: To systematically assess the clinical efficacy of high-frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) for treating pediatric acute respiratory distress syndrome (ARDS). METHODS: Data from randomized controlled trials comparing HFOV and CMV in the treatment of pediatric ARDS published before July 2016 were collected from the Cochrane Library, PubMed, Medline, CNKI, and Wanfang Data. Literature screening, data extraction, and quality assessment were performed by two independent reviewers according to the inclusion and exclusion criteria. The selected studies were then subjected to a Meta analysis using the RevMan 5.3 software. RESULTS: A total of 6 studies involving 246 patients were included. The results of the Meta analysis showed that there were no significant differences between the HFOV and CMV groups in the in-hospital or 30-day mortality rate, incidence of barotrauma, mean ventilation time, and oxygenation index (P>0.05). However, compared with CMV, HFOV increased the PaO2/FiO2 ratio by 17%, 24%, and 31% at 24, 48, and 72 hours after treatment respectively, and improved oxygenation in patients. CONCLUSIONS: Although the mortality rate is not reduced by HFOV in children with ARDS, this treatment can result in significant improvement in oxygenation compared with CMV. Further large-sample, multicenter, randomized clinical trials will be required to draw a definitive conclusion.


Assuntos
Ventilação de Alta Frequência , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/terapia , Humanos , Oxigênio/sangue , Síndrome do Desconforto Respiratório do Adulto/mortalidade
11.
Oncotarget ; 8(69): 113966-113976, 2017 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-29371961

RESUMO

Proximal symphalangism (SYM1) is an autosomal dominant disorder, mainly characterized by bony fusions of the proximal phalanges of the hands and feet. GDF5 and NOG were identified to be responsible for SYM1. We have previously reported on a p.Leu373Arg mutation in the GDF5 proregion present in a Chinese family with SYM1. Here, we investigated the effects of the GDF-L373R mutation. The variant caused proteolysis efficiency of GDF5 increased in ATDC5 cells. The variant also caused upregulation of SMAD1/5/8 phosphorylation and increased expression of target genes SMURF1, along with COL2A1 and SOX9 which are factors associated with chondrosis. Furthermore, we developed a human-relevant SYM1 mouse model by making a Gdf5L367R (the orthologous position for L373R in humans) knock-in mouse. Gdf5L367R/+ and Gdf5L367R/L367R mice displayed stiffness and adhesions across the proximal phalanx joint which were in complete accord with SYM1. It was also confirmed the joint formation and development was abnormal in Gdf5L367R/+ and Gdf5L367R/L367R mice, including the failure to develop the primary ossification center and be hypertrophic chondrocytes during embryonic development. This knock-in mouse model offers a tool for assessing the pathogenesis of SYM1 and the function of the GDF5 proregion.

12.
Zhonghua Nan Ke Xue ; 23(5): 441-447, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-29717836

RESUMO

Objective: To explore the risk factors for different types of hypospadias. METHODS: According to the 1∶1 ratio, we included hypospadias children in the case group and those without urinary abnormality as controls, all from the Third Affiliated Hospital of Zhengzhou University between October 2015 to October 2016. Using univariate and multivariate logistic regression analyses, we investigated the risk factors for hypospadias as well as for four different types of the disease. RESULTS: Among the 440 subjects, the risk factors for hypospadias included preterm birth, fetal growth restriction, rural residence of the mother, pregnancy age <20 or >35 years, primipara, maternal smoking (including passive smoking), oral progesterone, cold or fever during pregnancy, and exposure to high temperature in early pregnancy, while the protective factors included protein supplement in early pregnancy. The pregnancy age <20 or >35 years was the main risk factor for type I hypospadias; preterm birth, fetal growth restriction, rural residence of the mother, primipara, and maternal smoking (including passive smoking) during pregnancy were the risk factors for type Ⅱ; preterm birth, fetal growth restriction, rural residence of the mother, and exposure to high temperature in early pregnancy were those for type Ⅲ; and exposure to high temperature in early pregnancy and oral progesterone during pregnancy were those for type Ⅳ. CONCLUSIONS: The risk factors for hypospadias vary for different types, and therefore hypospadias-related clinical studies should be conducted and preventive measures should be taken accordingly. However, a larger sample size is needed to get more scientific and reliable results concerning the risk factors for different types of hypospadias.


Assuntos
Hipospadia/etiologia , Adulto , Feminino , Retardo do Crescimento Fetal , Humanos , Hipospadia/classificação , Recém-Nascido , Masculino , Idade Materna , Gravidez , Nascimento Prematuro , Análise de Regressão , Fatores de Risco , População Rural , Fumar , Adulto Jovem
13.
Appl Opt ; 53(24): 5264-74, 2014 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-25321095

RESUMO

This study focuses on injection molding process window determination for obtaining optimal imaging optical properties, astigmatism, coma, and spherical aberration using plastic lenses. The Taguchi experimental method was first used to identify the optimized combination of parameters and significant factors affecting the imaging optical properties of the lens. Full factorial experiments were then implemented based on the significant factors to build the response surface models. The injection molding process windows for lenses with optimized optical properties were determined based on the surface models, and confirmation experiments were performed to verify their validity. The results indicated that the significant factors affecting the optical properties of lenses are mold temperature, melt temperature, and cooling time. According to experimental data for the significant factors, the oblique ovals for different optical properties on the injection molding process windows based on melt temperature and cooling time can be obtained using the curve fitting approach. The confirmation experiments revealed that the average errors for astigmatism, coma, and spherical aberration are 3.44%, 5.62%, and 5.69%, respectively. The results indicated that the process windows proposed are highly reliable.

14.
Rev Sci Instrum ; 84(10): 103302, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24182102

RESUMO

Energy deposition in ionization chambers has been theoretically studied for tritium measurements in gaseous form. A one-dimension model is introduced to establish the quantitative relationship between energy deposition rate and many factors, including carrier gas, gas pressure, wall material, chamber size, and gas temperature. Energy deposition rate has been calculated at pressure varying from 5 kPa to 500 kPa based on some approximations. It is found that energy deposition rate varies greatly for different parameters, especially at low gas pressure. For the same chamber, energy deposition rate in argon is much higher than in deuterium, as much as 70.7% higher at 5 kPa. Gold plated chamber gives highest energy deposition rate in the calculations while aluminum chamber results in the lowest. As chamber size gets smaller, ß ray emitted by tritium will deposit less energy in the sensitive region of the chamber. For chambers flowing through with the same gas, energy deposition rate in a 10 L chamber is 23.9% higher than in a 0.05 L chamber at 5 kPa. Gas temperature also places slight influence on energy deposition rate, and 373 K will lead to 6.7% lower deposition rate than 233 K at 5 kPa. In addition, experiments have been performed to obtain energy deposition rate in a gold plated chamber, which show good accordance with theoretical calculations.

15.
Rev Sci Instrum ; 81(7): 073302, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20687712

RESUMO

An open-walled ionization chamber is developed to monitor the tritium concentration in gloveboxes in tritium processing systems. Two open walls are used to replace the sealed wall in common ionization chambers, through which the tritium gas can diffuse into the chamber without the aid of pumps and pipelines. Some basic properties of the chamber are examined to evaluate its performance. Results turn out that an open-walled chamber of 1 l in volume shows a considerably flat plateau over 700 V for a range of tritium concentration. The chamber also gives a good linear response to gamma fields over 4 decades under a pressure condition of 1 atm. The pressure dependence characteristics show that the ionization current is only sensitive at low pressures. The pressure influence becomes weaker as the pressure increases mainly due to the decrease in the mean free path of beta particles produced by tritium decay. The minimum detection limit of the chamber is 3.7x10(5) Bq/m(3).

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