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Mammalian brain tubulins undergo a reversible posttranslational modification-polyglutamylation-which attaches a secondary polyglutamate chain to the primary sequence of proteins. Loss of its erasers can disrupt polyglutamylation homeostasis and cause neurodegeneration. Tubulin tyrosine ligase like 4 (TTLL4) and TTLL7 were known to modify tubulins, both with preference for the ß-isoform, but differently contribute to neurodegeneration. However, differences in their biochemical properties and functions remain largely unknown. Here, using an antibody-based method, we characterized the properties of a purified recombinant TTLL4 and confirmed its sole role as an initiator, unlike TTLL7, which both initiates and elongates the side chains. Unexpectedly, TTLL4 produced stronger glutamylation immunosignals for α-isoform than ß-isoform in brain tubulins. Contrarily, the recombinant TTLL7 raised comparable glutamylation immunoreactivity for two isoforms. Given the site selectivity of the glutamylation antibody, we analyzed modification sites of two enzymes. Tandem mass spectrometry analysis revealed their incompatible site selectivity on synthetic peptides mimicking carboxyl termini of α1- and ß2-tubulins and a recombinant tubulin. Particularly, in the recombinant α1A-tubulin, a novel region was found glutamylated by TTLL4 and TTLL7, that again at distinct sites. These results pinpoint different site specificities between two enzymes. Moreover, TTLL7 exhibits less efficiency to elongate microtubules premodified by TTLL4, suggesting possible regulation of TTLL7 elongation activity by TTLL4-initiated sites. Finally, we showed that kinesin behaves differentially on microtubules modified by two enzymes. This study underpins the different reactivity, site selectivity, and function of TTLL4 and TTLL7 on brain tubulins and sheds light on their distinct role in vivo.
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Microtúbulos , Peptídeo Sintases , Tubulina (Proteína) , Animais , Encéfalo/metabolismo , Microtúbulos/metabolismo , Ácido Poliglutâmico/química , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Tubulina (Proteína)/metabolismo , Peptídeo Sintases/metabolismoRESUMO
All-inorganic lead halide perovskites (CsPbX3, X = Cl, Br or I) are becoming increasingly important for energy conversion and optoelectronics because of their outstanding performance and enhanced environmental stability. Morphing perovskites into specific shapes and geometries without damaging their intrinsic functional properties is attractive for designing devices and manufacturing. However, inorganic semiconductors are often intrinsically brittle at room temperature, except for some recently reported layered or van der Waals semiconductors. Here, by in situ compression, we demonstrate that single-crystal CsPbX3 micropillars can be substantially morphed into distinct shapes (cubic, L and Z shapes, rectangular arches and so on) without localized cleavage or cracks. Such exceptional plasticity is enabled by successive slips of partial dislocations on multiple [Formula: see text] systems, as evidenced by atomic-resolution transmission electron microscopy and first-principles and atomistic simulations. The optoelectronic performance and bandgap of the devices were unchanged. Thus, our results suggest that CsPbX3 perovskites, as potential deformable inorganic semiconductors, may have profound implications for the manufacture of advanced optoelectronics and energy systems.
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The peptide quantitative structure-activity relationship (QSAR), also known as the quantitative sequence-activity model (QSAM), has attracted much attention in the bio- and chemoinformatics communities and is a well developed computational peptidology strategy to statistically correlate the sequence/structure and activity/property relationships of functional peptides. Amino acid descriptors (AADs) are one of the most widely used methods to characterize peptide structures by decomposing the peptide into its residue building blocks and sequentially parametrizing each building block with a vector of amino acid principal properties. Considering that various AADs have been proposed over the past decades and new AADs are still emerging today, we herein query the following: is it necessary to develop so many AADs and do we need to continuously develop more new AADs? In this study, we exhaustively collect 80 published AADs and comprehensively evaluate their modeling performance (including fitting ability, internal stability, and predictive power) on 8 QSAR-oriented peptide sample sets (QPSs) by employing 2 sophisticated machine learning methods (MLMs), totally building and systematically comparing 1280 (80 AADs × 8 QPSs × 2 MLMs) peptide QSAR models. The following is revealed: (i) None of the AADs can work best on all or most peptide sets; an AAD usually performs well for some peptides but badly for others. (ii) Modeling performance is primarily determined by the peptide samples and then the MLMs used, while AADs have only a moderate influence on the performance. (iii) There is no essential difference between the modeling performances of different AAD types (physiochemical, topological, 3D-structural, etc.). (iv) Two random descriptors, which are separately generated randomly in standard normal distribution N(0, 1) and uniform distribution U(-1, +1), do not perform significantly worse than these carefully developed AADs. (v) A secondary descriptor, which carries major information involved in the 80 (primary) AADs, does not perform significantly better than these AADs. Overall, we conclude that since there are various AADs available to date and they already cover numerous amino acid properties, further development of new AADs is not an essential choice to improve peptide QSAR modeling; the traditional AAD methodology is believed to have almost reached the theoretical limit nowadays. In addition, the AADs are more likely to be a vector symbol but not informative data; they are utilized to mark and distinguish the 20 amino acids but do not really bring much original property information to these amino acids.
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Aminoácidos , Relação Quantitativa Estrutura-Atividade , Modelos Moleculares , PeptídeosRESUMO
OBJECTIVE: To explore the risk factors for different types of hypospadias. METHODS: According to the 1â¶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 â ¡; preterm birth, fetal growth restriction, rural residence of the mother, and exposure to high temperature in early pregnancy were those for type â ¢; and exposure to high temperature in early pregnancy and oral progesterone during pregnancy were those for type â £. 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.
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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 JovemRESUMO
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.
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Ventilação de Alta Frequência , Respiração Artificial , Síndrome do Desconforto Respiratório/terapia , Humanos , Oxigênio/sangue , Síndrome do Desconforto Respiratório/mortalidadeRESUMO
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.
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The effects of tritium at low doses and low dose rates have received increasing attention due to recent developments in fusion energy and the associated risks of tritium releases into the environment. Mitochondria have been identified as a potential candidate for studying the effects of low-dose/low-dose-rate radiation, with extensive experimental results obtained using X-ray irradiation. In this study, irradiation experiments were conducted on normal B-lymphoblastoid cells using HTO at varying doses. When compared to X-ray irradiation, no significant differences in cell viability induced by different doses were observed. However, the results of ATP levels showed a significant difference between the irradiated sample at a dose of 500 mGy by tritium beta-rays and the sham-irradiated sample, while the levels obtained with X-ray irradiation were almost identical to the sham-irradiated sample. In contrast, ATP levels for both tritium beta-rays and X-rays at a dose of 1.0 Gy showed minimal differences compared to the sham-irradiated sample. Furthermore, distinct effects at 500 mGy were also confirmed in both ROS levels and apoptosis results obtained through tritium beta-ray irradiation. This suggests that mitochondria might be a potential sensitive target for investigating the effects of tritium beta-ray irradiation.
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Controlled buckling of colloidal droplets via acoustic levitation plays an important role in pharmaceutical, coating, and material self-assembly. In this study, the evaporation process of PTFE colloidal droplets with two particle concentrations (60 wt% and 20 wt%) was investigated under acoustic levitation. We report the occurrence of surface invagination caused by evaporation. For the high particle concentration droplet, the upper surface was invaginated, eventually forming a bowl-shaped structure. While for the low particle concentration droplet, both the upper and lower surfaces of the droplet were invaginated, resulting in a doughnut-like structure. For the acoustically levitated oblate spherical droplet, the dispersant loss at the equatorial area of the droplet is greater than that at the two poles. Therefore, the thickness of the solid shell on the surface of the droplet was not uniform, resulting in invagination at the weaker pole area. Moreover, once the droplet surface was buckling, the hollow cavity on the droplet surface would absorb the sound energy and results in strong positive acoustic radiation pressure at bottom of the invagination, thus further prompting the invagination process.
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Bubble dynamics plays a significant role in a wide range of industrial fields, such as food, pharmacy and chemical engineering. The physicochemical properties of complex fluids can greatly affect the speed with which bubbles rise, and the lifetime of bubbles, which in turn can affect the efficiency of food and drug manufacturing and also sewage purification. Therefore, it is of great scientific and practical significance to study the influence mechanism of nanoparticles and surfactants on bubble rising and impact in a complex fluid interface. This paper selects a mixed dispersion liquid of nanoparticles (SiO2) and a surfactant (SDS) as the objects of the study, observes in real-time the entire processes of bubbles rising, impact at the gas-liquid interface, and rupture, and analyzes the dynamic mechanism of bubble impact in a complex fluid interface. By analyzing the morphological changes of the rising bubbles, the rising velocity and the lifetime of the bubbles, it is found that the surfactant molecules are distributed in the ultrapure water liquid pool and the liquid film surrounding the bubbles. Such distribution can reduce the viscoelasticity between bubbles and the liquid surface, and lower the surface tension of the liquid, which can reduce the rising velocity of bubbles, delay the drainage process of bubbles on a liquid surface, and enhance the lifetime of bubbles. If the liquid surface is covered with nanoparticles, a reticulate structure will be formed on the bubble liquid film, which can inhibit bubble discharge and prolong bubble lifetime. In addition, the influence of such a reticulate structure on liquid surface tension is limited and its function is far smaller than a surfactant.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiological agent of the current rapidly growing outbreak of coronavirus disease (COVID-19), which is straining health systems around the world. Disrupting the intermolecular association of SARS-CoV-2 spike glycoprotein (S protein) with its cell surface receptor human angiotensin-converting enzyme 2 (hACE2) has been recognized as a promising therapeutic strategy against COVID-19. The association is a typical peptide-mediated interaction, where the hACE adopts an α1-helix, which can form a two-helix bundle with the α2-helix, to pack against a flat pocket on the S protein surface. Here, we demonstrate that the protein context of full-length hACE plays an essential role in supporting the hACE2 α1-helix recognition by viral S protein. Energetic analysis reveals that the α1-helical peptide (αHP) and also the two-helix bundle peptide (tBP) cannot bind effectively to S protein when they are split from the hACE protein. The context contributes moderately and considerably to the direct readout (DR) and indirect readout (IR) of peptide recognition, respectively. Dynamics simulation suggests that the two free peptides exhibit a large intrinsic disorder without the support of protein context, which would incur a considerable entropy penalty upon binding to S protein. To restore the IR effect lost by splitting peptides from hACE, we herein propose employing hydrocarbon stapling and cyclization strategies to constrain the free αHP and tBP peptides into their native ordered conformations, respectively. The stapling and cyclization are carefully designed in order to avoid influencing the peptide DR effect, which has been demonstrated to improve the peptide binding affinity (but not specificity) to S protein. The stapling/cyclization-imposed conformational constraint can effectively minimize the unfavorable IR effect (i) by reducing the peptide flexibility and entropy cost upon their binding to S protein, and (ii) by helping peptide pre-folding into their native state to facilitate the conformational selection by S protein.
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Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Peptídeos/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Sítios de Ligação , Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Humanos , Simulação de Dinâmica Molecular , Peptídeos/química , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/genética , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
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.
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Domínios de Homologia de src , Quinases da Família src , Sequência de Aminoácidos , Sítios de Ligação , Proteína Tirosina Quinase CSK , Humanos , Peptídeos/metabolismo , Ligação Proteica , Quinases da Família src/genética , Quinases da Família src/metabolismoRESUMO
BACKGROUND: Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. METHODS: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). RESULTS: Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane®), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles. CONCLUSIONS: This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.
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Paclitaxel Ligado a Albumina/farmacologia , Antineoplásicos/farmacologia , Paclitaxel Ligado a Albumina/administração & dosagem , Paclitaxel Ligado a Albumina/efeitos adversos , Paclitaxel Ligado a Albumina/farmacocinética , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células , Química Farmacêutica , Portadores de Fármacos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas , Tamanho da Partícula , Distribuição Aleatória , Propriedades de SuperfícieRESUMO
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.
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Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/secundário , Vetores Genéticos/química , Vetores Genéticos/farmacologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Animais , Arginina , Ácido Aspártico , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Cisteína , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tamanho da Partícula , Fragmentos de Peptídeos , Peptídeo T , Polietilenoglicóis/química , Carga TumoralRESUMO
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.
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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.
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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.
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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.
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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.
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Peptídeos/química , Peptídeos/metabolismo , Domínios de Homologia de src , Quinases da Família src/química , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Proteína Tirosina Quinase CSK , Humanos , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica , Proto-Oncogene Mas , Relação Estrutura-Atividade , Termodinâmica , Quinases da Família src/metabolismoRESUMO
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.
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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.