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1.
Biochem Biophys Res Commun ; 719: 150042, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38761633

RESUMO

BACKGROUND & AIMS: Psychosocial stress has become an unavoidable part of life, which was reported to promote tumor development. Chronic stress significantly promotes the norepinephrine (NE) secretion and the expression of leptin receptor (LEPR), leading to tumor invasion, metastasis, and proliferation. However, the mechanism of chronic stress-induced tumor proliferation remains unclear. METHODS: To reveal the effect of chronic stress on tumor proliferation, subcutaneous tumor models combined with chronic restraint stress (CRS) were established. Combined with the transcript omics database of liver cancer patients, the target pathways were screened and further verified by in vitro experiments. RESULTS: The results showed that the CRS with subcutaneous tumor transplantation (CRS + tumor) group exhibited significantly larger tumor sizes than the subcutaneous tumor transplantation (tumor) group. Compared with the tumor group, CRS obviously increased the mRNA levels of LEPR, FOS, and JUNB of tumor tissues in the CRS + tumor group. Furthermore, the treatment with norepinephrine (NE) significantly elevated the survival rate of H22 cells and enhanced the expression of LEPR, FOS, and JUNB in vitro. Silencing LEPR significantly reduced the expression of FOS and JUNB, accompanied by a decrease in H22 cell viability. CONCLUSIONS: Our study demonstrated that CRS activates the LEPR-FOS-JUNB signaling pathway by NE, aggravating tumor development. These findings might provide a scientific foundation for investigating the underlying pathological mechanisms of tumors in response to chronic stress.


Assuntos
Proliferação de Células , Proteínas Proto-Oncogênicas c-fos , Receptores para Leptina , Transdução de Sinais , Receptores para Leptina/metabolismo , Receptores para Leptina/genética , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Masculino , Proteínas Proto-Oncogênicas c-jun/metabolismo , Estresse Psicológico/metabolismo , Restrição Física , Norepinefrina/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Camundongos Endogâmicos BALB C
2.
J Sci Food Agric ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38545944

RESUMO

BACKGROUND: Peanut peptides have good chelating ability with metal ions. However, there are few studies on the chelation mechanism of peanut peptides with calcium and absorption properties of peptide-calcium complex. RESULTS: Peptides with high calcium chelating rate were isolated and purified from peanut protein hydrolysate (PPH), and the chelation rate of component F21 was higher (81.4 ± 0.8%). Six peptides were identified from component F21 by liquid chromatography-tandem mass spectrometry, and the frequency of acidic amino acids and arginine in the amino acid sequence was higher in all six peptides. Peanut peptide-calcium complex (PPH21-Ca) was prepared by selecting component F21 (PPH21). Ultraviolet analysis indicated that the chelate reaction occurred between peanut peptide and calcium ions. Fourier transform infrared analysis showed that the chelating sites were carboxyl and amino groups on the amino acid residues of peptides. Scanning electron microscopy revealed that the surface of peanut peptide had a smooth block structure, but the surface of the complex had a granular morphology. Caco-2 cell model tests revealed that the bioavailability of PPH21-Ca was 58.4 ± 0.5%, which was significantly higher than that of inorganic calcium at 37.0 ± 0.4%. CONCLUSION: Peanut peptides can chelate calcium ions by carboxyl and amino groups, and the peptide-calcium complex had higher bioavailability. This study provides a theoretical basis for the development of new calcium supplement products that are absorbed easily. © 2024 Society of Chemical Industry.

3.
Anal Chem ; 95(15): 6358-6366, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37017602

RESUMO

Stress induced amorphous proteome aggregation is a hallmark for diseased cells, with the proteomic composition intimately associated with disease pathogenicity. Due to its particularly dynamic, reversible, and dissociable nature, as well as lack of specific recognition anchor, it is difficult to capture aggregated proteins in situ. In this work, we develop a chemical proteomics method (AggLink) to capture amorphous aggregated proteins in live stressed cells and identify the proteomic contents using LC-MS/MS. Our method relies on an affinity-based chemical probe (AggLink 1.0) that is optimized to selectively bind to and covalently label amorphous aggregated proteins in live stressed cells. Especially, chaotrope-compatible ligation enables effective enrichment of labeled aggregated proteins under urea denaturation and dissociation conditions. Compared to conventional fractionation-based method to profile aggregated proteome, our method showed improved enrichment selectivity, detection sensitivity, and identification accuracy. In HeLa cells, the AggLink method reveals the constituent heterogeneity of aggregated proteome induced by inhibition of pro-folding (HSP90) or pro-degradation (proteasome) pathway, which uncovers a synergistic strategy to reduce cancer cell viability. In addition, the unique fluorogenicity of our probe upon labeling aggregated proteome detects its cellular location and morphology. Together, the AggLink method may help to expand our knowledge of the previously nontargetable amorphous aggregated proteome.


Assuntos
Proteoma , Proteômica , Humanos , Proteoma/química , Células HeLa , Cromatografia Líquida/métodos , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos
4.
Hum Brain Mapp ; 44(6): 2365-2379, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36722495

RESUMO

Functional changes of default mode network (DMN) have been proven to be closely associated with white matter hyperintensity (WMH) related cognitive impairment (CI). However, subsystem mechanisms of DMN underlying WMH-related CI remain unclear. The present study recruited WMH patients (n = 206) with mild CI and normal cognition, as well as healthy controls (HC, n = 102). Static/dynamic functional connectivity (FC) of the DMN's three subsystems were calculated using resting-state functional MRI. K-means clustering analyses were performed to extract distinct dynamic connectivity states. Compared with the WMH-NC group, the WMH-MCI group displayed lower static FC within medial temporal lobe (MTL) and core subsystem, between core-MTL subsystem, as well as between core and dorsal medial prefrontal cortex subsystem. All these static alterations were positively associated with information processing speed (IPS). Regarding dynamic FC, the WMH-MCI group exhibited higher dynamic FC within MTL subsystem than the HC and WMH-NC groups. Altered dynamic FC within MTL subsystem mediated the relationship between WMH and memory span (indirect effect: -0.2251, 95% confidence interval [-0.6295, -0.0267]). Additionally, dynamic FCs of DMN subsystems could be clustered into two recurring states. For dynamic FCs within MTL subsystem, WMH-MCI subjects exhibited longer mean dwell time (MDT) and higher reoccurrence fraction (RF) in a sparsely connected state (State 2). Altered MDT and RF in State 2 were negatively associated with IPS. Taken together, these findings indicated static/dynamic FC of DMN subsystems can provide relevant information on cognitive decline from different aspects, which provides a comprehensive view of subsystem mechanisms of DMN underlying WMH-related CI.


Assuntos
Disfunção Cognitiva , Substância Branca , Humanos , Encéfalo/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Rede de Modo Padrão/diagnóstico por imagem , Imageamento por Ressonância Magnética
5.
Small ; 19(48): e2303646, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37528507

RESUMO

Molybdenum disulfide (MoS2 ) has been proved as an excellent potential hydrogen evolution reaction (HER) catalyst. Compared with thermodynamically stable 2H-MoS2 , 1T-MoS2 exhibits higher conductivity and catalytic activity, whereas it is usually difficult to prepare since of thermodynamically metastable. Herein, a feasible method is reported to fabricate ambient-stable MoS2 with high concentration 1T phase through magnetic free energy synergistic microstrain induced by W doping under low magnetic field. The 1T phase proportion in MoS2 can be as high as 80% and is ambient-stable for more than one year. The catalyst prepared under a magnetic field of 3 T delivers an overpotential of 195 mV at a current density of 10 mA cm-2 and has a long-term stability over 50 h. This work provides a novel strategy for preparation of MoS2 with high 1T concentration and high stability.

6.
Small ; : e2308729, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38078778

RESUMO

Compared with crystalline molybdenum sulfide (MoS2 ) employed as an efficient hydrogen evolution reaction (HER) catalyst, amorphous MoSx exhibits better activity. To synthesize amorphous MoSx , electrodeposition serving as a convenient and time-saving method is successfully applied. However, the loading mass is hindered by limited mass transfer efficiency and the available active sites require further improvement. Herein, magneto-electrodeposition is developed to synthesize MoSx with magnetic fields up to 9 T to investigate the effects of a magnetic field in the electrodeposition processing, as well as the induced electrochemical performance. Owing to the magneto-hydrodynamic effect, the loading mass of MoSx is obviously increased, and the terminal S2- serving as the active site is enhanced. The optimized MoSx catalyst delivers outstanding HER performance, achieving an overpotential of 50 mV at a current density of 10 mA cm-2 and the corresponding Tafel slope of 59 mV dec-1 . The introduction of a magnetic field during the electrodeposition process will provide a novel route to prepare amorphous MoSx with improved electrochemical performance.

7.
Glob Chang Biol ; 29(21): 6139-6156, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37641440

RESUMO

Robust estimates of wetland soil organic carbon (SOC) pools are critical to understanding wetland carbon dynamics in the global carbon cycle. However, previous estimates were highly variable and uncertain, due likely to the data sources and method used. Here we used machine learning method to estimate SOC storage and their changes over time in China's wetlands based on wetland SOC density database, associated geospatial environmental data, and recently published wetland maps. We built a database of wetland SOC density in China that contains 809 samples from 181 published studies collected over the last 20 years as presented in the published literature. All samples were extended and standardized to a 1-m depth, on the basis of the relationship between SOC density data from soil profiles of different depths. We used three different machine learning methods to evaluate their robustness in estimating wetland SOC storage and changes in China. The results indicated that random forest model achieved accurate wetland SOC estimation with R2 being .65. The results showed that average SOC density of top 1 m in China's wetlands was 25.03 ± 3.11 kg C m-2 in 2000 and 26.57 ± 3.73 kg C m-2 in 2020, an increase of 6.15%. SOC storage change from 4.73 ± 0.58 Pg in 2000 to 4.35 ± 0.61 Pg in 2020, a decrease of 8.03%, due to 13.6% decreased in wetland area from 189.12 × 103 to 162.8 × 103 km2 in 2020, despite the increase in SOC density during the same time period. The carbon accumulation rate was 107.5 ± 12.4 g C m-2 year-1 since 2000 in wetlands with no area changes. Climate change caused variations in wetland SOC density, and a future warming and drying climate would lead to decreases in wetland SOC storage. Estimates under Shared Socioeconomic Pathway 1-2.6 (low-carbon emissions) suggested that wetland SOC storage in China would not change significantly by 2100, but under Shared Socioeconomic Pathway 5-8.5 (high-carbon emissions), it would decrease significantly by approximately 5.77%. In this study, estimates of wetland SOC storage were optimized from three aspects, including sample database, wetland extent, and estimation method. Our study indicates the importance of using consistent SOC density and extent data in estimating and projecting wetland SOC storage.

8.
J Am Chem Soc ; 144(30): 13794-13805, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35830296

RESUMO

In the context of sustainable development, chirality, especially chiral drugs, has attracted great interest in the pharmaceutical industry, yet the smart and sensitive separation of enantiomers still presents a major scientific challenge. Herein, inspired by supramolecular templating via chiral transcription nanoparticles, an artificial chiral nanochannel membrane with asymmetric structure, porosity, and abundant chiral surface is fabricated for smart and sensitive enantiomer recognition and separation. Constructed from chiral transcript mesoporous silica (CMS) super-assembled on a porous anode alumina oxide (AAO) support, the obtained heterostructured chiral membrane (CMS/AAO) exhibits enhanced enantioseparation (approximately 170% compared to the supramolecular-templated nanoparticles) among a series of amino acids with various isoelectric points (PIs). Especially for amino acids with a PI greater than 7, the couple-accelerated enantioseparation (CAE) can be achieved for the first time. Further analysis using an osmotic energy conversion test and simulations based on the Poisson-Nernst-Planck (PNP) equations confirm that the heterostructure and charge polarity are the key to achieve chiral amino acids and ion separation. We expect this work will inspire the development of multifunctional membrane systems for more sustainable and energy-efficient enantioseparation.


Assuntos
Nanopartículas , Dióxido de Silício , Aminoácidos , Porosidade , Dióxido de Silício/química , Estereoisomerismo
9.
Anal Chem ; 94(14): 5591-5598, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35348340

RESUMO

High-cost viral nucleic acid detection devices (e.g., qPCR system) are limited resources for developing counties and rural areas, leading to underdiagnosis or even pandemics of viral infectious diseases. Herein, a novel virus detection strategy is reported. Such detection method is enabled by TR512-peptide-based biorthogonal capture and enrichment of commercially available Texas red fluorophore labeled nucleic acid on the functionalized paper. The GST-TR512 fusion protein electrostatically immobilized on the paper is constructed to retain the binding affinity of TR512-peptide toward Texas red fluorophore labeled nucleic acid released in the preamplification process, then the enrichment of analytes enhances fluorescence signal for rapid detection as volume of sample filters through the paper. The method is generally applicable to different nucleic acid preamplification strategies (PCR, RAA, CRISPR) and different virus types (Hepatitis B virus (HBV), African swine fever virus (ASFV), human papillomavirus (HPV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or 2019 nCoV)). Finally, a full-set virus detection device is developed in house to detect the presence of Hepatitis B virus (HBV) viral gene in patients' blood samples. Taken together, we first apply TR512-peptide in the signal enrichment and the novel detection strategy may offer an inexpensive, rapid, and portable solution for areas with limited access to a standard diagnosis laboratory.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , COVID-19 , Ácidos Nucleicos , Febre Suína Africana/diagnóstico , Vírus da Febre Suína Africana/genética , Animais , COVID-19/diagnóstico , Corantes Fluorescentes , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Peptídeos/genética , SARS-CoV-2/genética , Sensibilidade e Especificidade , Suínos
10.
Small ; 18(5): e2104460, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35112501

RESUMO

3D anisotropic functional properties (such as magnetic, electrical, thermal, and optical properties, etc.) in a single material are not only beneficial to the multipurpose of a material, but also helpful to enrich the regulatory dimensionality of functional materials. Herein, a colossal 3D electrical anisotropy of layered MAB-phase MoAlB single crystal is introduced and dissected. Using high-temperature metal-solution method, high-quality MoAlB single crystals are obtained and a surprisingly strong out-of-plane (σa /σb  = 1.43 × 105 , at 2 K) and in-plane (σa /σc  = 12.12, at 2 K) electrical anisotropies are first observed. After a series of experimental and theoretical investigations, it is demonstrated that the 3D anisotropic crystal structure and chemical bond of MoAlB result in its 3D anisotropic phonon vibration and electronic structure, influence the corresponding electron-electron as well as electron-phonon interactions, and finally give rise to its colossal 3D anisotropy of electrical conductivity. This work experimentally and theoretically proves MoAlB single crystal possessing the 3D anisotropies of crystal structure, chemical bond, phonon vibration, electronic structure, and electrical transport, but also provides a promising platform for the future design of functionalized electronic devices as well as synthesis of new and large-sized in-plane anisotropic 2D material (MoBene).

11.
Plant Physiol ; 187(4): 2296-2310, 2021 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-34601582

RESUMO

AKT2 potassium (K+) channels are members of the plant Shaker family which mediate dual-directional K+ transport with weak voltage-dependency. Here we show that OsAKT2 of rice (Oryza sativa) functions mainly as an inward rectifier with strong voltage-dependency and acutely suppressed outward activity. This is attributed to the presence of a unique K191 residue in the S4 domain. The typical bi-directional leak-like property was restored by a single K191R mutation, indicating that this functional distinction is an intrinsic characteristic of OsAKT2. Furthermore, the opposite R195K mutation of AtAKT2 changed the channel to an inward-rectifier similar to OsAKT2. OsAKT2 was modulated by OsCBL1/OsCIPK23, evoking the outward activity and diminishing the inward current. The physiological relevance in relation to the rectification diversity of OsAKT2 was addressed by functional assembly in the Arabidopsis (Arabidopsis thaliana) akt2 mutant. Overexpression (OE) of OsAKT2 complemented the K+ deficiency in the phloem sap and leaves of the mutant plants but did not significantly contribute to the transport of sugars. However, the expression of OsAKT2-K191R overcame both the shortage of phloem K+ and sucrose of the akt2 mutant, which was comparable to the effects of the OE of AtAKT2, while the expression of the inward mutation AtAKT2-R195K resembled the effects of OsAKT2. Additionally, OE of OsAKT2 ameliorated the salt tolerance of Arabidopsis.


Assuntos
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Oryza/genética , Oryza/metabolismo , Floema/metabolismo , Canais de Potássio/metabolismo , Tolerância ao Sal/fisiologia , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Mutação , Floema/genética , Canais de Potássio/genética , Tolerância ao Sal/genética
12.
Mutagenesis ; 37(1): 34-43, 2022 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-34791379

RESUMO

Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate-deficient (22.6 nM) and replete (2260 nM) Roswell Park Memorial Institute (RPMI)-1640 medium with or without 50 µM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 µM) and standard (2.26 µM) medium with 200 µM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 µM DCA or LCA significantly increased the rate of micronuclei (MN) in NCM460 and L-02 cells. Significantly, the MN-inducing effect of 50 µM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of MN, nucleoplasmic bridges, nuclear buds, apoptosis, and necrosis induced by 200 µM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 µM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 µM).


Assuntos
Ácidos e Sais Biliares , Dano ao DNA , Colo , Ácido Fólico/farmacologia , Humanos , Fígado , Testes para Micronúcleos/métodos
13.
Molecules ; 27(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35684393

RESUMO

For the high-valued utilization of hemicelluloses and for realizing the controllable synthesis of NPs, this paper's aim is to combine xylan, chitosan and nanometal materials at the same time. In this research study, firstly, propargyl xylan was synthesized via nucleophilic substitution reaction between xylan and propargyl bromide in NaOH solution. On the other hand, a tosyl group was introduced onto the 6th position of synthesized quaternized chitosan (QCS), and the azide group replaced the tosyl group to obtain 6-amido-QCS (QCS-N3). The synthesis conditions of the above reactions were optimized. Subsequently, the novel xylan-click-QCS polymer was obtained via click reaction between terminal alkyne groups on the xylan chains and azide groups on QCS. Then, AgNPs and AuNPs were synthesized by adopting the xylan-click-QCS polymer as the reducing and stabilizing agent, and the reaction conditions were optimized to obtain well-dispersed and highly stable nanoparticles. There were two kinds of Ag nanomaterials, with diameters of 10~20 nm and 2~5 nm, respectively, indicating the formation of Ag nanoclusters, except for Ag nanoparticles, in this reaction. The diameter of the synthesized AuNPs was 20~30 nm, which possessed a more uniform size distribution. The Ag nanoclusters with a smaller size (2~5 nm) could inhibit MCF-7 cell proliferation effectively, indicating their application potential in cancer therapy. The study gives a new approach to the high-value utilization of biopolymers.


Assuntos
Quitosana , Nanopartículas Metálicas , Azidas , Química Click , Ouro , Polímeros , Prata , Xilanos
14.
Biochemistry ; 60(32): 2447-2456, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34369156

RESUMO

The turbidity assay is commonly exploited to study protein liquid-to-liquid phase separation (LLPS) or liquid-to-solid phase separation (LSPS) processes in biochemical analyses. Herein, we present common pitfalls of this assay caused by exceeding the detection linear range. We showed that aggregated proteins of high concentration and large particle size can lead to inaccurate quantification in multiple applications, including the optical density measurement, the thermal shift assay, and the dynamic light scattering experiment. Finally, we demonstrated that a simple sample dilution of insoluble aggregated protein (LSPS) samples or direct imaging of liquid droplets (LLPS) can address these issues and improve the accuracy of the turbidity assay.


Assuntos
Fracionamento Químico/métodos , Nefelometria e Turbidimetria/métodos , Proteínas/química , Proteínas/isolamento & purificação , Amiloide/análise , Amiloide/química , Difusão Dinâmica da Luz , Cinética , Limite de Detecção , Tamanho da Partícula , Agregados Proteicos , Análise Espectral
15.
Anal Chem ; 93(3): 1717-1724, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33382253

RESUMO

Stress-induced intracellular proteome aggregation is a hallmark and a biomarker of various human diseases. Current sensors requiring either cellular fixation or covalent modification of the entire proteome are not suitable for live-cell applications and dynamics study. Herein, we report a noncovalent, cell-permeable, and fluorogenic sensor that can reversibly bind to proteome amorphous aggregates and monitor their formation, transition, and clearance in live cells. This sensor was structurally optimized from previously reported fluorescent protein chromophores to enable noncovalent and reversible binding to aggregated proteins. Unlike all previous sensors, the noncovalent and reversible nature of this probe allows for dynamic detection of both the formation and clearance of aggregated proteome in one live-cell sample. Under different cellular stresses, this sensor reveals drastic differences in the morphology and location of aggregated proteome. Furthermore, we have shown that this sensor can detect the transition from proteome liquid-to-liquid phase separation to liquid-to-solid phase separation in a two-color imaging experiment. Overall, the sensor reported here can serve as a facile tool to screen therapeutic drugs and identify cellular pathways that ameliorate pathogenic proteome aggregation in live-cell models.


Assuntos
Corantes Fluorescentes/química , Proteoma/química , Técnicas Biossensoriais , Células HEK293 , Humanos , Estrutura Molecular , Imagem Óptica , Agregados Proteicos , Solubilidade , Espectrometria de Fluorescência
16.
Anal Chem ; 93(49): 16447-16455, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34859995

RESUMO

Common solvatochromic fluorophores exhibit a bathochromic fluorescence emission wavelength shift accompanied by intensity attenuation due to the presence of nonradiative decay pathways at the excited state. Such intrinsic but inevitable fluorescence quenching of solvatochromism impedes its applications to faithfully quantify local polarity, especially in a polar environment. Herein, we report a new donor-π-acceptor (D-π-A) type solvatochromic fluorophore scaffold containing a perfluorophenyl group that exhibits both a solvatochromic emission wavelength shift and a controllable emission intensity upon polarity fluctuation. The regulation of fluorescence solvatochromism and colors was achieved by tuning the aryl donors. We exploited such desired solvatochromism of these probes to monitor protein misfolding and aggregation via wavelength shift. Finally, the polarity of pathogenic aggregated proteins was quantified by HaloTag bioorthogonal labeling technology in live cells. While much effort has been devoted to resolving the morphology of pathogenic aggregated proteins, this work provides quantitative hints regarding the chemical information at this disease-related protein interphase.


Assuntos
Corantes Fluorescentes , Agregados Proteicos , Fluorescência , Ionóforos , Proteínas
17.
Bioorg Med Chem Lett ; 52: 128408, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626785

RESUMO

Nowadays, with an upward trend in the prevalence of intracerebral amyloidosis, it is of great significance to use fluorescent probes for early diagnosis in vitro. In this study, a quinoline-derived D-A-D type chemosensor was rationally designed and synthesized as a probe for the sensitive detection of tetrameric transthyretin (WT-TTR).


Assuntos
Corantes Fluorescentes/química , Pré-Albumina/análise , Quinolinas/química , Corantes Fluorescentes/síntese química , Humanos , Estrutura Molecular , Quinolinas/síntese química
18.
BMC Med Imaging ; 21(1): 158, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717573

RESUMO

BACKGROUND: To investigate value of the quantitative perfusion parameters of dynamic triple-phase enhanced CT in differential diagnosis of pulmonary lesions, and explore the correlation between perfusion parameters of lung cancer with microvessel density (MVD) and vascular endothelial growth factor (VEGF). METHODS: 73 consecutive patients with lung lesions who successfully underwent pre-operative CT perfusion examination with dynamic triple-phase enhanced CT and received a final diagnosis by postoperative pathology or a clinical follow-up. The cases were divided into malignant and benign groups according to the pathological results. CT perfusion parameters, such as Median, Mean, Standard deviation (Std), Q10, Q25, Q50, Q75, Q90 of pulmonary artery perfusion (PAP), bronchial artery perfusion (BAP), perfusion index (PI) and arterial enhancement fraction (AEF) were obtained by performing computed tomography perfusion imaging (CTPI). Computed tomography perfusion (CTP) parameters were compared between malignant and benign lesions. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of CTP parameters in diagnosing malignant lesions. The correlations between CTP parameters with MVD and VEGF were analysed in 36 lung cancer patients who had extra sections be used for immunohistochemistry staining of CD34 and VEGF. RESULTS: BAP (Mean, Std, Q90) and PI Std of benign lesions were higher than malignant lesions (p < 0.05), and PAP (Q10, Q25), PI (Median, Mean, Q10, Q25, Q50) of malignant lesions were higher than the benign (p < 0.05). The area under the ROC curve of PI Mean, PI Q10 and PI Std was 0.722 (95% CI = [0.595-0.845]), 0.728 (95% CI = [0.612-0.844]) and 0.717 (95% CI = [0.598-0.835]) respectively. Partial perfusion parameters of BAP and AEF Q10 were positively correlated with MVD (p value range is < 0.001-0.037, ρ value range is 0.483-0.683), and partial perfusion parameters of PI were negatively correlated with MVD (p value range is 0.001-0.041,ρvalue range is - 0.523-- 0.343). Partial perfusion parameters of BAP and AEF Q10 were positively correlated with VEGF (p value range is 0.001-0.016, ρvalue range is 0.398-0.570), meanwhile some perfusion parameters of PAP and PI were negatively correlated with VEGF (p value range is 0.001-0.040, ρ value range is - 0.657-0.343). CONCLUSIONS: Quantitative parameters of dynamic triple-phase enhanced CT can provide diagnostic basis for the differentiation of lung lesions, and there were connection with tumor angiogenesis and vascular endothelial growth factor expression.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Neovascularização Patológica/diagnóstico por imagem , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Ácidos Tri-Iodobenzoicos
19.
BMC Med Imaging ; 21(1): 73, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865336

RESUMO

BACKGROUND: To explore if the quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlates with the expression of PTEN, P-Akt and m-TOR protein in lung cancer. METHODS: Thirty-three patients with 33 lesions who had been diagnosed with lung cancer were enrolled in this study. They were divided into three groups: squamous cell carcinoma (SCC, 15 cases), adenocarcinoma (AC, 12 cases) and small cell lung cancer (SCLC, 6 cases). Preoperative imaging (conventional imaging and DCE-MRI) was performed on all patients. The Exchange model was used to measure the phar- macokinetic parameters, including Ktrans, Vp, Kep, Ve and Fp, and then the histogram parameters meanvalue, skewness, kurtosis, uniformity, energy, entropy, quantile of above five parameters were analyzed. The expression of PTEN, P-Akt and m-TOR were assessed by immunohistochemistry. Spearman correlation analysis was used to compare the correlation between the quantitative perfusion histogram parameters and the expression of PTEN, P-Akt and m-TOR in different pathological subtypes of lung cancer. RESULTS: The expression of m-TOR (P = 0.013) and P-Akt (P = 0.002) in AC was significantly higher than those in SCC. Vp (uniformity) in SCC group, Ktrans (uniformity), Ve (kurtosis, Q10, Q25) in AC group, Fp (skewness, kurtosis, energy), Ve (Q75, Q90, Q95) in SCLC group was positively correlated with PTEN, and Fp (entropy) in the SCLC group was negatively correlated with PTEN (P < 0.05); Kep (Q5, Q10) in the SCLC group was positively correlated with P-Akt, and Kep (energy) in the SCLC group was negatively correlated with P-Akt (P < 0.05); Kep (Q5) in SCC group and Vp (meanvalue, Q75, Q90, Q95) in SCLC group was positively correlated with m-TOR, and Ve (meanvalue) in SCC group was negatively correlated with m-TOR (P < 0.05). CONCLUSIONS: The quantitative perfusion histogram parameters of DCE-MRI was correlated with the expression of PTEN, P-Akt and m-TOR in different pathological types of lung cancer, which may be used to indirectly evaluate the activation status of PI3K/Akt/mTOR signal pathway gene in lung cancer, and provide important reference for clinical treatment.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Adenocarcinoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Meios de Contraste , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Imagem de Perfusão/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Serina-Treonina Quinases TOR/metabolismo
20.
Molecules ; 26(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440748

RESUMO

Adsorption kinetic studies are conducted to investigate the potential to use chiral mesoporous materials nanoporous guanosine monophosphate material-1 (NGM-1) and nanoporous folic acid material-1 (NFM-1) for the enantiomeric separation of l- and d-valine. A pseudo-second-order (PSO) kinetic model is applied to test the experimental adsorption equilibrium isotherms, according to both the Langmuir and Freundlich models and the characteristic parameters for each model are determined. The calcined versions of both NGM-1 and NFM-1 fit the Langmuir model with maximum sorption capacities of 0.36 and 0.26 g/g for the preferred adsorption enantiomers, d-valine and l-valine, respectively. Experimental results and the analysis of adsorption models suggest a strong adsorbate-adsorbent interaction, and the formation of a monolayer of tightly packed amino acid on the internal mesopore surface for the preferred enantiomers.


Assuntos
Ácido Fólico/química , Guanosina Monofosfato/química , Nanoestruturas/química , Dióxido de Silício/química , Valina/isolamento & purificação , Adsorção , Cinética , Nanoporos/ultraestrutura , Nanoestruturas/ultraestrutura , Porosidade , Estereoisomerismo , Valina/análise
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