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The performance of tin halide perovskite solar cells (PSCs) has been severely limited by the rapid crystallization of tin perovskites, which usually leads to an undesirable film quality. In this work, we tackle this issue by regulating the nucleation and crystal growth of tin perovskite films using a small Lewis base additive, urea. The urea-SnI2 interaction facilitates the formation of larger and more uniform clusters, thus accelerating the nucleation process. Additionally, the crystal growth process is extended, resulting in a high-quality tin perovskite film with compact morphology, increased crystallinity, and reduced defects. Consequently, the efficiency of tin PSCs is significantly increased from 10.42% to 14.22%. This work highlights the importance of manipulating the nucleation and crystal growth of tin perovskites to realize efficient tin PSCs.
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All-inorganic cesium lead triiodide perovskites (CsPbI3) have attracted increasing attention due to their good thermal stability, remarkable optoelectronic properties, and adaptability in tandem solar cells. However, N2-filled glovebox is generally required to strictly control the humidity during film fabrication due to the moisture-induced black-to-yellow phase transition, which remains a great hinderance for further commercialization. Herein, we report an effective approach via incorporating multifunctional ethacridine lactate (EAL) to mitigate moisture invasion and enable the fabrication of efficient inverted (p-i-n) CsPbI3 perovskite solar cells (PSCs) under ambient condition. It is revealed that the lactate anions accelerate the crystallization of CsPbI3, shortening the exposure time to moisture during film fabrication. Meanwhile, the conjugated backbone and multiple functional groups in the ethacridine cations can interact with I- and Pb2+ to reduce the undesired defects, stabilize the perovskite structure and facilitate the charge transport in the film. Moreover, EAL incorporation also leads to better energy alignment, thus favoring charge extraction at both upper and bottom interfaces. Consequently, the device efficiency and stability are enormously enhanced, with the champion efficiency reaching 21.08 %. This even surpasses the highest value reported for the devices fabricated in glovebox, representing a record efficiency of inverted all-inorganic PSCs.
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Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.
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Dissecção Aórtica , RNA de Interação com Piwi , Humanos , Camundongos , Animais , Nicotina/farmacologia , Proliferação de Células , Dissecção Aórtica/tratamento farmacológico , Dissecção Aórtica/genética , Aorta , Miócitos de Músculo Liso/metabolismo , Células CultivadasRESUMO
Cardiovascular disease (CVD) has overtaken infectious illnesses as the leading cause of mortality and disability worldwide. The pathology that underpins CVD is atherosclerosis, characterized by chronic inflammation caused by the accumulation of plaques in the arteries. As our knowledge about the microenvironment of blood vessel walls deepens, there is an opportunity to fine-tune treatments to target the mechanisms driving atherosclerosis more directly. The application of non-coding RNAs (ncRNAs) as biomarkers or intervention targets is increasing. Although these ncRNAs play an important role in driving atherosclerosis and vascular dysfunction, the cellular and extracellular environments pose a challenge for targeted transmission and therapeutic regulation of ncRNAs. Specificity, delivery, and tolerance have hampered the clinical translation of ncRNA-based therapeutics. Nanomedicine is an emerging field that uses nanotechnology for targeted drug delivery and advanced imaging. Recently, nanoscale carriers have shown promising results and have introduced new possibilities for nucleic acid targeted drug delivery, particularly for atherosclerosis. In this review, we discuss the latest developments in nanoparticles to aid ncRNA-based drug development, particularly miRNA, and we analyze the current challenges in ncRNA targeted delivery. In particular, we highlight the emergence of various kinds of nanotherapeutic approaches based on ncRNAs, which can improve treatment options for atherosclerosis.
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Aterosclerose , Doenças Cardiovasculares , MicroRNAs , Aterosclerose/genética , Aterosclerose/terapia , Biomarcadores , Doenças Cardiovasculares/genética , Humanos , MicroRNAs/genética , RNA não Traduzido/genéticaRESUMO
With the widespread use of electrical equipment, cognitive functions such as working memory (WM) could be severely affected when people are exposed to 50 Hz electromagnetic fields (EMF) for long term. However, the effects of EMF exposure on WM and its neural mechanism remain unclear. In the present paper, 15 rats were randomly assigned to three groups, and exposed to an EMF environment at 50 Hz and 2 mT for a different duration: 0 days (control group), 24 days (experimental group I), and 48 days (experimental group II). Then, their WM function was assessed by the T-maze task. Besides, their local field potential (LFP) in the media prefrontal cortex (mPFC) was recorded by the in vivo multichannel electrophysiological recording system to study the power spectral density (PSD) of θ and γ oscillations and the phase-amplitude coupling (PAC) intensity of θ-γ oscillations during the T-maze task. The results showed that the PSD of θ and γ oscillations decreased in experimental groups I and II, and the PAC intensity between θ and high-frequency γ (hγ) decreased significantly compared to the control group. The number of days needed to meet the task criterion was more in experimental groups I and II than that of control group. The results indicate that long-term exposure to EMF could impair WM function. The possible reason may be the impaired communication between different rhythmic oscillations caused by a decrease in θ-hγ PAC intensity. This paper demonstrates the negative effects of EMF on WM and reveals the potential neural mechanisms from the changes of PAC intensity, which provides important support for further investigation of the biological effects of EMF and its mechanisms.
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Campos Eletromagnéticos , Memória de Curto Prazo , Humanos , Ratos , Animais , Memória de Curto Prazo/fisiologia , Campos Eletromagnéticos/efeitos adversos , Córtex Pré-Frontal , CogniçãoRESUMO
Cutting tool wear state assessment during the manufacturing process is extremely significant. The primary purpose of this study is to monitor tool wear to ensure timely tool change and avoid excessive tool wear or sudden tool breakage, which causes workpiece waste and could even damage the machine. Therefore, an intelligent system, that is efficient and precise, needs to be designed for addressing these problems. In our study, an end-to-end improved fine-grained image classification method is employed for workpiece surface-based tool wear monitoring, which is named efficient channel attention destruction and construction learning (ECADCL). The proposed method uses a feature extraction module to extract features from the input image and its corrupted images, and adversarial learning is used to avoid learning noise from corrupted images while extracting semantic features by reconstructing the corrupted images. Finally, a decision module predicts the label based on the learned features. Moreover, the feature extraction module combines a local cross-channel interaction attention mechanism without dimensionality reduction to characterize representative information. A milling dataset is conducted based on the machined surface images for monitoring tool wear conditions. The experimental results indicated that the proposed system can effectively assess the wear state of the tool.
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The removal of low concentration ammonia-nitrogen in industrial wastewater is necessary before discharged into the environment. In this study, vacuum plate membrane distillation (VPMD) technology was utilized and operating parameters such as pH, feed temperature, vacuum degree, feed flow and time were investigated. Based on the experimental data, the heat and mass transfer mechanism and mathematic model were studied. The experimental results show that low solution pH was significantly beneficial to ammonia-nitrogen removal but permeate flux was nearly changeless. At pH = 4, a removal rate up to 93.33% was achieved. Ammonia-nitrogen mainly exists with NH4+ ions in acidic solution, so only water molecules pass through the membrane to acquire the water product in the permeate side. Increasing the temperature of the solution was disadvantageous to the ammonia-nitrogen removal due to membrane pores expanding and the mass transfer coefficient of NH3 molecules increasing; therefore a low temperature was chosen if possible. Because vapor pressure of the feed solution increases exponentially with temperature and results in membrane surface pressure difference increases, therefore increasing the temperature enhances the permeate flux. Raising the vacuum degree enhanced ammonia removal rate and permeate flux obviously, a vacuum degree of 0.09 MPa was chosen for the experiment. The effect of feed flow rate on ammonia-nitrogen removal instead of permeate flux is weak, the reason is that the boundary layer wears thin when the feed flow rate is increased, which is conducive to permeate flux increasing. In a two-parameter model of Knudsen diffusion, Poiseuille flow was chosen to demonstrate the heat and mass transfers in the process of VPMD in the study. Based on the experimental values of permeate flux, two parameters CK and CP in the model were calculated using a nonlinear fitting method software, which indicated that the Knudsen diffusion model more than the Poiseuille flow model was suitable. The maximum values of the relative average deviation (RAD) and root mean square difference (RMSD) of experimental and calculated values with model equations of the permeate flux at the different temperature, vacuum degree and feed flow rate were no more than 8.7% and 3.20 kg · (m2 · h)-1, respectively.
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Destilação , Purificação da Água , Destilação/métodos , Águas Residuárias/química , Amônia , Vácuo , Membranas Artificiais , Purificação da Água/métodos , Nitrogênio , Água , TecnologiaRESUMO
In recent years, exploring the physiological and pathological mechanisms of brain functional integration from the neural network level has become one of the focuses of neuroscience research. Due to the non-stationary and nonlinear characteristics of neural signals, its linear characteristics are not sufficient to fully explain the potential neurophysiological activity mechanism in the implementation of complex brain functions. In order to overcome the limitation that the linear algorithm cannot effectively analyze the nonlinear characteristics of signals, researchers proposed the transfer entropy (TE) algorithm. In recent years, with the introduction of the concept of brain functional network, TE has been continuously optimized as a powerful tool for nonlinear time series multivariate analysis. This paper first introduces the principle of TE algorithm and the research progress of related improved algorithms, discusses and compares their respective characteristics, and then summarizes the application of TE algorithm in the field of electrophysiological signal analysis. Finally, combined with the research progress in recent years, the existing problems of TE are discussed, and the future development direction is prospected.
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Algoritmos , Dinâmica não Linear , Encéfalo/fisiologia , Entropia , Redes Neurais de ComputaçãoRESUMO
Metal nanoparticles (NPs) are promising bonding materials to replace Sn alloys in fine size Cu-Cu bonding. However, the method of rapidly patterning NPs on solder joints with sizes less than 30 µm is one of the main barriers that impede the practical applications of NPs in Cu-Cu bonding, especially in mass production. In this paper, a novel method of patterning Ag NPs on Cu pads by selective wetting was introduced. Cu pads with diameters down to 5 µm were coated with Ag NPs successfully. When sizes of Cu pads were larger than 10 µm, high density could be achieved and the ratio of diameters to pitches of Cu pads could reach 2/3. Furthermore, the thickness and the coverage of the Ag NPs layer could be raised by repeating coating. In the bonding test, the shear strength increased significantly with the increase of the bonding temperature and the bonding time. It could reach 22.92 MPa after sintering for 5 min at 250 °C under a bonding pressure of 20 MPa in N2. With the aforementioned advantages, patterning NPs by selective wetting will be one of the potential methods for applying NPs to Cu pads in Cu-NPs-Cu bonding.
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BACKGROUND: Bursopentin (BP5) is a multifunctional pentapeptide found in the chicken bursa of Fabricius. Recent study indicated that BP5 significantly stimulates expression of p53 protein in colon cancer HCT116 cells. However, the effects and underlying mechanisms of BP5 on HCT116 cell proliferation remain largely unclear. METHODS: Analyses of cell viability, cell cycle arrest as well as apoptosis were performed to study the actions of BP5 on HCT116 cells. Western blot analyse was assayed to measure the cell cycle-related and apoptosis-related proteins. Specific siRNAs targeting IRE1, ATF-6, and PERK were used for IRE1, ATF-6, and PERK knockdown, respectively. Cellular reactive oxygen species (ROS) were detected using a H2DCF-DA green fluorescence probe. Cytosolic free Ca2+ concentrations and mitochondrial membrane potential (ΔΨm) were measured using Fluo-3 AM and JC-1 stains, respectively. RESULTS: BP5 possessed strong inhibitory effects on the cell growth and induced apoptosis in HCT116 cells. Mechanistically, BP5 arrested the cell cycle at G1 phase by increasing p53 and p21 expression and decreasing cyclin E1-CDK2 complex expression. BP5 treatment dramatically activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway, as revealed by the significantly enhanced expression of unfolded protein response (UPR) sensors (IRE1α, ATF6, PERK) as well as downstream signaling molecules (XBP-1s, eIF2α, ATF4 and CHOP), and by the significantly altered the BP5-induced phenotypic changes in IRE1, ATF6, and PERK knockdown cells. Additionally, BP5-induced ER stress was accompanied by the accumulation of cytosolic free Ca2+ and intracellular ROS. Furthermore, BP5 treatment resulted in the increase of Bax expression, the decrease of Bcl-2 expression and the reduction of ΔΨm, subsequently causing a release of cytochrome c from the mitochondria into the cytoplasm and finally enhancing the activities of caspase-9 and -3. In addition, z-VAD-fmk, a pan-caspase inhibitor, markedly rescued BP5-induced cell viability reduction and reduced BP5-induced apoptosis. CONCLUSIONS: Our present results suggest that BP5 has an anticancer capacity to arrest cell cycle at G1 phase and to trigger ER stress/mitochondria-mediated caspase-dependent apoptosis in HCT116 cells. Therefore, our findings provide insight into further investigations of the anticancer activities of BP5.
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Organic anion transporters 1 (OAT1) and 3 (OAT3) play important roles in the renal elimination of a range of substrate molecules. Little is known about natural products that can modulate OAT1 and OAT3 activities. The medullae of Juncus effusus is often used for the treatment of dysuria in traditional Chinese medicine. To study the interactions of phytochemicals in J. effusus with human OAT1 and OAT3, a bioactivity guided phytochemical investigation led to seven new phenanthrenoids along with nine known compounds, including eight phenanthrenoids and a benzophenone from the dichloromethane soluble fraction of a methanol extract of the medullae of J. effusus. The structures were established by physical data analysis, including high-resolution electrospray ionization mass spectrometry and 1D and 2D NMR. The compounds were evaluated for inhibition of OAT1 and OAT3 in vitro. Compounds 10 and 16 were inhibitors for OAT1, and compounds 1-3, 10, and 16 were inhibitors for OAT3 with IC50 values less than 5.0 µM. Dihydrophenanthrene 1 markedly altered the pharmacokinetic parameters of the diuretic drug furosemide, a known substrate of both OAT1 and OAT3, in vivo.
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Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Fenantrenos/farmacologia , Animais , Células HEK293 , Humanos , Masculino , Fenantrenos/química , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Wistar , Análise Espectral/métodos , Relação Estrutura-AtividadeRESUMO
Quality assessment of Cortex Periplocae remains a challenge, due to its complex chemical profile. This study aims to investigate the chemical components of Cortex Periplocae, including its non-volatile and volatile constituents, via liquid chromatograph-mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) assays. The established strategy manifested that Cortex Periplocae from different producing areas was determined by identifying 27 chemical markers with ultra-high-performance liquid chromatography, coupled with quadrupole tandem time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), including four main groups of cardiac glycosides, organic acids, aldehydes, and oligosaccharides. These groups' variable importance in the projection (VIP) were greater than 1. Simultaneously, the samples were divided into four categories, combined with multivariate statistical analysis. In addition, in order to further understand the difference in the content of samples from different producing areas, nine chemical markers of Cortex Periplocae from 14 different producing areas were determined by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS), and results indicated that the main effective constituents of Cortex Periplocae varied with places of origin. Furthermore, in GC-MS analysis, samples were divided into three groups with multivariate statistical analysis; in addition, 22 differential components whose VIP were greater than 1 were identified, which were principally volatile oils and fatty acids. Finally, the relative contents of seven main volatile constituents were obtained, which varied extremely with the producing areas. The results showed that the LC-MS/MS and GC-MS assays, combined with multivariate statistical analysis for Cortex Periplocae, provided a comprehensive and effective means for its quality evaluation.
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Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Periploca/química , Compostos Fitoquímicos/química , Casca de Planta/química , Extratos Vegetais/química , Raízes de Plantas/química , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Cromatografia Gasosa-Espectrometria de Massas , Periploca/classificação , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em TandemRESUMO
To determine the potential tumor suppressor functions of ubiquitin-specific protease 10 (USP10) in lung cancer and elucidate underlying molecular mechanism. The relative expression of USP10 was determined by real-time PCR and immunoblotting. The inhibitory effect of USP10 on tumor growth was demonstrated on allograft mice with Lewis carcinoma cell inoculation. The relative cell proliferation was measured with Cell Counting Kit-8 (CCK-8). The invasive capacity was evaluated by transwell assay. The interaction between USP10 and Phosphatase And Tensin Homolog (PTEN) was examined by co-immunoprecipitation. Ubiquitination/deubiquitination was analyzed by immunoprecipitation followed by immunoblotting. USP10 was down-regulated in lung cancer. Knockdown of USP10 promotes tumor growth and invasion both in vitro and in vivo. We further demonstrated that USP10 directly interacted with and stabilized PTEN via deubiquitination. The pro-cancerous effect of USP10 deficiency was abolished by re-introduction of PTEN. We suggested a tumor suppressor function of USP10 in lung cancer via deubiquitinating and stabilizing PTEN.
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Carcinoma Pulmonar de Lewis/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , PTEN Fosfo-Hidrolase/biossíntese , Ubiquitina Tiolesterase/metabolismo , Regulação para Cima , Células A549 , Animais , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/genética , Ubiquitina Tiolesterase/genéticaRESUMO
Nardostachys jatamansi is a well-documented herbal agent used to treat digestive and neuropsychiatric disorders in oriental medicinal systems. However, few simple, rapid, and comprehensive methods were reported for quality assessment and control of N. jatamansi. Herein, a UPLC with photodiode array detection method was developed for both fingerprint investigation of N. jatamansi and simultaneous quantitative analysis of the six serotonin transporter modulatory constituents in N. jatamansi. For chromatographic fingerprinting, 24 common peaks were selected as characteristic peaks to assess the consistency of N. jatamansi samples from different retail sources. Six of the common peaks (5, 7, 12: , and 16: â-â18: ) were identified as desoxo-narchinol A, buddleoside, isonardosinone, nardosinone, kanshone H, and (-)-aristolone, respectively, by phytochemical investigation. Five of the six compounds significantly either enhanced or inhibited serotonin transporter activity, while (-)-aristolone (18: ) didn't show any serotonin transporter activity. In quantitative analysis, the six compounds showed good linearity (r > 0.999) within test ranges. The precision, expressed as relative standard deviation, was in the range of 0.25â-â2.77%, and the recovery of the method was in the range of 92â-â105%. The UPLC-photodiode array detection-based fingerprint analysis and quantitative methods reported here could be used for routine quality control of N. jatamansi.
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Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Nardostachys/química , Controle de QualidadeRESUMO
The use of concentrated samples is usually avoided during conventional separations since utilization of concentrated samples normally compromises the quality of separation. However, in case of the detection of low-abundance components, highly concentrated samples are necessary, which leads to an extremely high concentration for high-abundant components. This will make the separation difficult due to the serious longitudinal dispersion. Here, we developed a method to separate high concentration of components based on the modified capillary electrophoresis. The mechanism involves concentrated sample stretched into a wider zone in the higher electric field strength; the sample zone is fractionated into thin sections via a cutting effect; these thin sections are then separated. Based on this mechanism, we examined to separate an overloaded mixture of N,N'-diphenylguanidine and N,N'-di(o-tolyl)guanidine. Baseline separation was achieved due to much small longitudinal dispersion. The theoretical plate numbers of peaks were around 3.5 × 105 m-1 . The practicality of the new approach is demonstrated in the separation of a model protein mixture, containing lysozyme, bovine serum albumin, and ribonuclease A.
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Eletroforese Capilar , Muramidase/isolamento & purificação , Ribonuclease Pancreático/isolamento & purificação , Soroalbumina Bovina/isolamento & purificaçãoRESUMO
Four new iridoids, 2'-O-(E)-coumaroylshanzhiside (1), 6'-O-(E)-coumaroylshanzhiside (2), 8α-butylgardenoside B (3), 6α-methoxygenipin (4), and one new phenylpropanoid glucoside, 5-(3-hydroxypropyl)-2-methoxyphenyl ß-d-glucopyranoside (5), together with sixteen known compounds, were isolated from the edible flowers of wild Gardenia jasminoides J.Ellis. Their chemical structures were characterized by extensive spectroscopic techniques, including 1D- and 2D-NMR, HR-ESI-MS, and CD experiments. The absolute configurations of the new isolates' sugar moiety were assigned by HPLC analysis of the acid hydrolysates. Furthermore, the antioxidant activities of those isolates were preliminarily evaluated by DPPH scavenging experiment. And comparison of 1 H-NMR spectra for the EtOH extract of G. jasminoides J.Ellis, gardenoside B and geniposide revealed that the flowers of this plant have a considerable content of gardenoside B instead of geniposide in the fruits, indicating different activities and applications in people's daily life.
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Gardenia/química , Extratos Vegetais/análise , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flores/química , Frutas/química , Iridoides/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/química , Análise EspectralRESUMO
Reduction in the sample complexity enables more thorough intact protein analysis using MS-based proteomics. A capillary electrophoresis method, namely the velocity gap mode of capillary electrophoresis (VGCE), is proposed to separate protein mixtures with high resolution. Although the separation mechanism of VGCE is also based on the difference of the mass-to-charge ratios of the proteins, it fractionates the sample zone into small pieces of subunits. In this way, the resolution can be dramatically improved due to less longitudinal dispersion of the sample. The effect of the new approach is evaluated by separation of three groups of reference protein mixtures, i.e. a mixture of lysozyme and BSA; a mixture of lysozyme, ß-lactoglobulin, and ribonuclease A; and a mixture of cytochrome C, lysozyme, BSA, ß-lactoglobulin, ribonuclease A, conalbumin, carbonic anhydrase, and hemoglobin. The results indicate that the new approach shows great potential to couple with MS for top-down analysis of complex mixtures.
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Eletroforese Capilar/métodos , Proteínas/isolamento & purificação , Animais , Bovinos , Eletroforese Capilar/normas , Estudos de Viabilidade , Padrões de ReferênciaRESUMO
Two new lignan glycosides, ussuriensislignan A (1) and ussuriensislignan B (2), together with seventeen known compounds (3-19), were isolated from the fruits of Pyrus ussuriensis. Their structures were determined by various spectroscopic methods. This is the first report of the isolation of lignans (compounds 1-3) from the genus Pyrus, and compounds 3-6, 12-16 were reported from Pyrus for the first time.
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Medicamentos de Ervas Chinesas/isolamento & purificação , Frutas/química , Glicosídeos/isolamento & purificação , Lignanas/isolamento & purificação , Pyrus/química , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Lignanas/química , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Saturated bicyclic amines are increasingly targeted to the pharmaceutical industry as sp3-rich bioisosteres of anilines. Numerous strategies have been established for the preparation of bridgehead aminobicyclics. However, methods to assemble the bridge-amino hydrocarbon skeleton, which serves as a meta-substituted arene bioisostere, are limited. Herein, a general approach to access 2-aminobicyclo[2.1.1]hexanes (aminoBCHs) by titanium-catalyzed formal [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes and 2-azadienes was developed. Simple derivatization of aminoBCHs leads to various medicinally and agrochemically important analogues.
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Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule-targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi-interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart-apoptosis-associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea-derived plant exosome-like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir-HAAPIR-nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir-HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi-interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle-encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.