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1.
Food Chem ; 366: 130586, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311229

RESUMO

In this study, the gluten/zein nanofibrous films were fabricated by blending electrospinning and then glycated with xylose via Maillard reaction. The average fiber diameter of the gluten film decreased from 551 to 343 nm with the increasing ratio of zein, but increased significantly to a range of 717-521 nm after glycation, which induced a higher thermal stability of the nanofibers with an order to disorder transition. The glycated composite films showed the reduced water vapor permeability and improved water stability with a stiffer and more elastic network structure, due to the enhanced intermolecular entanglements and interactions between polymer chains. The results from this work suggested that the composite gluten/zein electrospun films may be glycated via Maillard reaction to obtain desirable physical properties for active food-packaging applications.

2.
Food Chem ; 367: 130751, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34384987

RESUMO

Wheat bran is a rich source of phenolic compounds, and the health benefits of phenolic compounds depend on its bioaccessibility. The release behavior and functional properties of phenolic compounds in different particle size wheat bran during in vitro digestion were investigated. Coarse wheat bran (CWB, 1110.39 µm) was milled by airflow impact mill to produce medium wheat bran (MWB, 235.68 µm), fine wheat bran (FWB, 83.73 µm) and superfine wheat bran (SWB, 19.16 µm). The reduction in particle size increased the release of phenolic compounds, mainly ferulic acid, after digestion. The free p-coumaric acid content in SWB was nearly five times higher than that in CWB, MWB and FWB due to the complete destruction of aleurone cell walls. Moreover, SWB showed higher bioaccessible phenolic compounds content (65.51%) than CWB. The improved phenolic bioaccessibility increased the antioxidant capacities and carbohydrate-digestive enzymes inhibitory activities of SWB and significantly reduced its starch digestibility.

3.
Chem Asian J ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472705

RESUMO

A convenient protocol for the synthesis of quinoline-4-carbaldehydes via chemoselective oxidation of 4-methylquinolines using hypervalent iodine(III) reagents as oxidant is described. This method highlights metal-free and mild reaction conditions, nice yield, good functional group tolerance, and high chemoselectivity.

4.
Cell Biol Toxicol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524571

RESUMO

Chemotherapy resistance is an important problem for clinical therapy of osteosarcoma (OS). The potential effects of histone deacetylases (HDACs) on OS chemoresistance are studied. The expression of HDACs in OS cells resistance to doxorubicin (Dox) and cisplatin (CDDP) is checked. Among 11 members of HDACs, levels of HDAC6 are significantly upregulated in OS cells resistance to Dox and CDDP. Inhibition of HDAC6 via its specific inhibitor ACY1215 restores chemosensitivity of OS-resistant cells. Further, HDAC6 directly binds with estrogen-related receptors alpha (ERRα) to regulate its acetylation and protein stability. Inhibition of ERRα further strengthens ACY1215-increased chemosensitivity of OS-resistant cells. Mechanistically, K129 acetylation is the key residue for HDAC6-regulated protein levels of ERRα. Collectively, we find that ERRα contributes to HDAC6-induced chemoresistance of OS cells. Inhibition of HDAC6/ERRα axis might be a potential approach to overcome chemoresistance and improve therapy efficiency for OS treatment. 1. HDAC6 was significantly upregulated in Dox and CDDP resistant OS cells; 2. Inhibition of HDAC6 can restore chemosensitivity of OS cells; 3. HDAC6 binds with ERRα at K129 to decrease its acetylation and increase protein stability; 4. ERRα contributes to HDAC6-induced chemoresistance of OS cells.

5.
J Colloid Interface Sci ; 606(Pt 2): 1311-1321, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34492468

RESUMO

Constructing noble metal-doped g-C3N4/carbon composites is a feasible route to overcome the intrinsic drawbacks of pristine g-C3N4 for enhanced activity of CO2 photoreduction. Herein, a novel Ag-doped g-C3N4/biomass-derived carbon composite with hollow bird's nest-like (Ag-g-C3N4/BN-C) is designed and prepared via a simple yet effective one-step pyrolysis method. In the Ag-g-C3N4/BN-C, the highly-dispersed Ag nanoparticles (20-30 nm) with the surface plasmon resonance (SPR) effect act as a significant cocatalyst not only to efficiently trap the photogenerated electrons from g-C3N4 to boost the separation of photogenerated electron-hole pairs but also to produce additional active "hot electrons", while the conductive quasi-spherical hollow structure of BN-C doubles the specific surface area with multiple reflections of light, providing abundant active sites and more utilization efficiency of light energy. As a result, the Ag-g-C3N4/BN-C exhibits a remarkably enhanced CO evolution rate of 33.3 µmol·g-1·h-1 without addition of any sacrificial reagents and photosensitizers, superior to those of both the pristine g-C3N4 and many reported g-C3N4-based counterparts. The findings of this work demonstrate a good indication for integrating g-C3N4 with SPR-dependence noble metal and renewable biomass-derived carbon for enhanced CO2 photoreduction, which may be extended to modify other semiconductor materials for more photocatalytic applications with enhanced activity.

6.
BMC Genom Data ; 22(1): 35, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535071

RESUMO

BACKGROUND: China is the birthplace of the deer family and the country with the most abundant deer resources. However, at present, China's deer industry faces the problem that pure sika deer and hybrid deer cannot be easily distinguished. Therefore, the development of a SNP identification chip is urgently required. RESULTS: In this study, 250 sika deer, 206 red deer, 23 first-generation hybrid deer (F1), 20 s-generation hybrid deer (F2), and 20 third-generation hybrid deer (F3) were resequenced. Using the chromosome-level sika deer genome as the reference sequence, mutation detection was performed on all individuals, and a total of 130,306,923 SNP loci were generated. After quality control filtering was performed, the remaining 31,140,900 loci were confirmed. From molecular-level and morphological analyses, the sika deer reference population and the red deer reference population were established. The Fst values of all SNPs in the two reference populations were calculated. According to customized algorithms and strict screening principles, 1000 red deer-specific SNP sites were finally selected for chip design, and 63 hybrid individuals were determined to contain red deer-specific SNP loci. The results showed that the gene content of red deer gradually decreased in subsequent hybrid generations, and this decrease roughly conformed to the law of statistical genetics. Reaction probes were designed according to the screening sites. All candidate sites met the requirements of the Illumina chip scoring system. The average score was 0.99, and the MAF was in the range of 0.3277 to 0.3621. Furthermore, 266 deer (125 sika deer, 39 red deer, 56 F1, 29 F2,17 F3) were randomly selected for 1 K SNP chip verification. The results showed that among the 1000 SNP sites, 995 probes were synthesized, 4 of which could not be typed, while 973 loci were polymorphic. PCA, random forest and ADMIXTURE results showed that the 1 K sika deer SNP chip was able to clearly distinguish sika deer, red deer, and hybrid deer and that this 1 K SNP chip technology may provide technical support for the protection and utilization of pure sika deer species resources. CONCLUSION: We successfully developed a low-density identification chip that can quickly and accurately distinguish sika deer from their hybrid offspring, thereby providing technical support for the protection and utilization of pure sika deer germplasm resources.

7.
PLoS Genet ; 17(9): e1009785, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34506481

RESUMO

Dysregulation of cardiac transcription programs has been identified in patients and families with heart failure, as well as those with morphological and functional forms of congenital heart defects. Mediator is a multi-subunit complex that plays a central role in transcription initiation by integrating regulatory signals from gene-specific transcriptional activators to RNA polymerase II (Pol II). Recently, Mediator subunit 30 (MED30), a metazoan specific Mediator subunit, has been associated with Langer-Giedion syndrome (LGS) Type II and Cornelia de Lange syndrome-4 (CDLS4), characterized by several abnormalities including congenital heart defects. A point mutation in MED30 has been identified in mouse and is associated with mitochondrial cardiomyopathy. Very recent structural analyses of Mediator revealed that MED30 localizes to the proximal Tail, anchoring Head and Tail modules, thus potentially influencing stability of the Mediator core. However, in vivo cellular and physiological roles of MED30 in maintaining Mediator core integrity remain to be tested. Here, we report that deletion of MED30 in embryonic or adult cardiomyocytes caused rapid development of cardiac defects and lethality. Importantly, cardiomyocyte specific ablation of MED30 destabilized Mediator core subunits, while the kinase module was preserved, demonstrating an essential role of MED30 in stability of the overall Mediator complex. RNAseq analyses of constitutive cardiomyocyte specific Med30 knockout (cKO) embryonic hearts and inducible cardiomyocyte specific Med30 knockout (icKO) adult cardiomyocytes further revealed critical transcription networks in cardiomyocytes controlled by Mediator. Taken together, our results demonstrated that MED30 is essential for Mediator stability and transcriptional networks in both developing and adult cardiomyocytes. Our results affirm the key role of proximal Tail modular subunits in maintaining core Mediator stability in vivo.

8.
Ecotoxicol Environ Saf ; 225: 112724, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509162

RESUMO

Compared to other soil remediation technologies, Cd-contaminated farmland soil with low cadmium accumulation (LCA) plant-based safe utilization is more catered to developing countries with food in high demand. Hormesis, which describes the fortification of plant growth performance by a low level of environmental stress, can be innovatively used to achieve increases in crop yield and plant functional components, thus amplifying the safe utilization efficiency of low Cd-contaminated soil by LCA plants. In the present study, the growth and physiological responses of Polygonatum sibiricum, a traditional Chinese medicinal herb, were investigated under laboratory conditions of gradient Cd dosage concentrations and times. As a result, the growth performance of P. sibiricum reached the peak of an inverse U-shaped curve of hormesis under e0 mg kg-1 and 9 months of Cd stress, with elevations in tuber biomass (medicinal part), plant height and polysaccharide content (medicinal components) of 143%, 25% and 90%, respectively. Meanwhile, trace Cd accumulation (0.41 mg kg-1) in the tuber guaranteed medicinal edible safety. In addition, Cd-induced hormesis in P. sibiricum was verified to be overcompensated by antioxidation systems. In conclusion, such 'win-win' results, including low Cd accumulation and enhancement of plant pharmaceutical value, provided medicinal herbs with a possibility for safe soil utilization.

9.
IEEE Trans Cybern ; PP2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478394

RESUMO

Data-driven fault detection and isolation (FDI) depends on complete, comprehensive, and accurate fault information. Optimal test selection can substantially improve information achievement for FDI and reduce the detecting cost and the maintenance cost of the engineering systems. Considerable efforts have been worked to model the test selection problem (TSP), but few of them considered the impact of the measurement uncertainty and the fault occurrence. In this article, a conditional joint distribution (CJD)-based test selection method is proposed to construct an accurate TSP model. In addition, we propose a deep copula function which can describe the dependency among the tests. Afterward, an improved discrete binary particle swarm optimization (IBPSO) algorithm is proposed to deal with TSP. Then, application to an electrical circuit is used to illustrate the efficiency of the proposed method over two available methods: 1) joint distribution-based IBPSO and 2) Bernoulli distribution-based IBPSO.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34492178

RESUMO

Perovskite light-emitting diodes (LEDs) show great potential for next-generation lighting and display technology. Despite intensive studies on single-color devices, there are few reports on perovskite-based white LEDs (Pe-WLEDs). Here, an efficient Pe-WLED based on a blue perovskite and an orange phosphorescent emitter is reported for the first time. It is found that using a simple perovskite/phosphor bilayer emitting structure, there is inefficient energy transfer from the blue perovskite to the orange phosphor, leading to low efficiency and a significant color shift with driving voltage. We address this issue by introducing a quantum-well-like charge-confinement structure for enhancing carrier trapping and thus exciton formation in the phosphorescent emitter. As a result, a high external quantum efficiency of 10.81% is obtained. More interestingly, by tuning the dopant concentration of the phosphorescent emitter using this simple device structure, we can controllably get Pe-WLEDs with very stable white light for display applications or tunable color from warm white to daylight for lighting applications.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34494427

RESUMO

Synergetic therapy includes the combination of two or more conventional therapeutic approaches and can be used for tumor treatment by combining the advantages and avoiding the drawbacks of each type of treatment. In the present study, truncated tissue factor (tTF)-EG3287 fusion protein-encapsulated gold nanorod (GNR)-virus-inspired mesoporous silica core-shell nanoparticles (vinyl hybrid silica nanoparticles; VSNP) (GNR@VSNP-tTF-EG3287) were synthesized to achieve synergetic therapy by utilizing selective vascular thrombosis therapy (SVTT) and photothermal therapy (PTT). By integrating the targeted coagulation activity of tTF-EG3287 and the high tumor ablation effect of GNR@VSNP, local hyperthermia could induce a high percentage of apoptosis of vascular endothelial cells by using near-infrared light. This provided additional phospholipid sites for tTF-EG3287 and enhanced its procoagulant activity in vitro. In addition, the nanoparticles, which had unique topological viral structures, exhibited superior cellular uptake properties leading to significant antitumor efficacy. The in vivo antitumor results further demonstrated an interaction between SVTT and PTT, whereas the synergetic therapy (SVTT and PTT) achieved an enhanced effect, which was superior to the respective treatment efficacy of each modality or the additive effect of their individual efficacies. In summary, the synthesized GNR@VSNP-tTF-EG3287 exerted synergetic effects and enhanced the antitumor efficiency by avoiding multiple injections and suboptimal administration. These effects simultaneously affected both tumor blood supply and cancer cell proliferation. The data suggested that the integration of SVTT induced by tTF-EG3287 and PTT could provide potential strategies for synergetic tumor therapy.

12.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502195

RESUMO

Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals for tumor cell growth and surrounding angiogenesis. In this process, the tumor-associated protein Annexin A2 interacts with STAT3 and promotes Tyr705 phosphorylation and STAT3 transcriptional activation. In this study, we found that (20S) ginsenoside Rh2 (G-Rh2), a natural compound inhibitor of Annexin A2, inhibited STAT3 activity in HepG2 cells. (20S) G-Rh2 interfered with the interaction between Annexin A2 and STAT3, and inhibited Tyr705 phosphorylation and subsequent transcriptional activity. The inhibitory activity of STAT3 leaded to the negative regulation of the four VEGFs, which significantly reduced the enhanced growth and migration ability of HUVECs in co-culture system. In addition, (20S)G-Rh2 failed to inhibit STAT3 activity in cells overexpressing (20S)G-Rh2 binding-deficient Annexin A2-K301A mutant, further proving Annexin A2-mediated inhibition of STAT3 by (20S)G-Rh2. These results indicate that (20S)G-Rh2 is a potent inhibitor of STAT3, predicting the potential activity of (20S)G-Rh2 in targeted therapy applications.

13.
PLoS One ; 16(9): e0257130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34506549

RESUMO

In recent years, text sentiment analysis has attracted wide attention, and promoted the rise and development of stance detection research. The purpose of stance detection is to determine the author's stance (favor or against) towards a specific target or proposition in the text. Pre-trained language models like BERT have been proven to perform well in this task. However, in many reality scenes, they are usually very expensive in computation, because such heavy models are difficult to implement with limited resources. To improve the efficiency while ensuring the performance, we propose a knowledge distillation model BERTtoCNN, which combines the classic distillation loss and similarity-preserving loss in a joint knowledge distillation framework. On the one hand, BERTtoCNN provides an efficient distillation process to train a novel 'student' CNN structure from a much larger 'teacher' language model BERT. On the other hand, based on the similarity-preserving loss function, BERTtoCNN guides the training of a student network, so that input pairs with similar (dissimilar) activation in the teacher network have similar (dissimilar) activation in the student network. We conduct experiments and test the proposed model on the open Chinese and English stance detection datasets. The experimental results show that our model outperforms the competitive baseline methods obviously.

14.
Drug Deliv ; 28(1): 1769-1784, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34470548

RESUMO

Traditional combined photodynamic and photothermal therapy (PDT/PTT) was limited in clinical treatment of cancer due to the exceptionally low drug delivery efficiency to tumor sites and the activation by laser excitation with different wavelengths. We have accidentally discovered that our synthesized chlorin e6-C-15-ethyl ester (HB, a new type of photosensitizer) be activated by a laser with an excitation wavelength of 660 nm. Herein, we utilized Au nanorods (AuNRs) as 660 nm-activated PTT carriers to be successively surface-functionalized with HB and tumor-targeting peptide cyclic RGD (cRGD) to develop HB-AuNRs@cRGD for single NIR laser-induced targeted PDT/PTT. The HB-AuNRs@cRGD could be preferentially accumulated within tumor sites and rapidly internalized by cancer cells. Thereby, the HB-AuNRs@cRGD could exhibit amplified therapeutic effects by producing both significant reactive oxygen species (ROS) and hyperthermia simultaneously under the guidance of fluorescence imaging. The tumor inhibition rate on ECA109 esophageal cancer model was approximately 77.04%, and the negligible systematic toxicity was observed. This study proposed that HB-AuNRs@cRGD might be a promising strategy for single NIR laser-induced and imaging-guided targeted bimodal phototherapy.

15.
Elife ; 102021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488939

RESUMO

As our ancestors migrated throughout different continents, natural selection increased the presence of alleles advantageous in the new environments. Heritable variations that alter the susceptibility to diseases vary with the historical period, the virulence of the infections, and their geographical spread. In this study we built polygenic scores for heritable traits that influence the genetic adaptation in the production of cytokines and immune-mediated disorders, including infectious, inflammatory, and autoimmune diseases, and applied them to the genomes of several ancient European populations. We observed that the advent of the Neolithic was a turning point for immune-mediated traits in Europeans, favoring those alleles linked with the development of tolerance against intracellular pathogens and promoting inflammatory responses against extracellular microbes. These evolutionary patterns are also associated with an increased presence of traits related to inflammatory and auto-immune diseases.

16.
Oxid Med Cell Longev ; 2021: 9978206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497684

RESUMO

Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we constructed a circRNA-associated competitive endogenous RNA (ceRNA) network to investigate the regulatory mechanism of LUAD procession and further constructed a prognostic signature to predict overall survival for LUAD patients. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network. Based on the TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs, and 49 DEmRNAs. GO and KEGG enrichment indicated that the ceRNA network might be involved in the regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate Cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using the LASSO method in the TCGA-LUAD training cohort. By applying the signature, patients could be categorized into the high-risk or low-risk subgroups with significant survival differences (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent GEO cohort (GSE42127, HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Multivariate Cox regression analysis proved that the three-gene signature was an independent prognostic factor. Combining the three-gene signature with clinical characters, a nomogram was constructed. The primary and external verification C-indexes were 0.717 and 0.716, respectively. The calibration curves for the probability of 3- and 5-year OS showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and further constructed a useful prognostic signature to guide personalized treatment of LUAD patients.

17.
J Mater Chem B ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505606

RESUMO

Rapid technology development and economic growth have brought attention to public health issues, such as food safety and environmental pollution, which creates an ever-increasing demand for fast and portable sensing technologies. Portable surface-enhanced Raman spectroscopy (SERS) capable of various analyte detection with low concentration in a convenient manner shows advantages in sensing technology including enhanced diagnostic precision, improved diagnostic efficiency, reduced diagnostic cost, and alleviation of patient pain, which emerges as a promising candidate for point-of-care testing (POCT). SERS detection technology based on different nanostructures made of noble metal-based nanomaterials can increase the sensitivity of Raman scattering by 6-8 orders of magnitude, making Raman based trace detection possible, and greatly promote the application scenarios of portable Raman spectrometers. In this perspective, we provide an overview of fundamental knowledge about the SERS mechanism including chemical and electromagnetic field enhancement mechanisms, the design and fabrication of SERS substrates based on materials, progress of using SERS for POCT in biochemical sensing and its clinical applications. Furthermore, we present the prospective of developing new nanomaterials with different functionalities for advanced SERS substrates, as well as the future advancement of biomedical sensing and clinical potential of SERS technology.

18.
Front Immunol ; 12: 662171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512620

RESUMO

Circulatory inflammatory proteins play a significant role in anti-Candida host immune defence. However, little is known about the genetic variation that contributes to the variability of inflammatory responses in response to C. albicans. To systematically characterize inflammatory responses in Candida infection, we profiled 91 circulatory inflammatory proteins in peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans yeast isolated from 378 individuals of European origin from the 500 Functional Genomics (500FG) cohort of the Human Functional Genomics Project (HFGP) and Lifelines Deep cohort. To identify the genetic factors that determine variation in inflammatory protein responses, we correlated genome-wide single nucleotide polymorphism (SNP) genotypes with protein abundance (protein quantitative trait loci, pQTLs) produced by the Candida-stimulated PBMCs. Furthermore, we investigated whether differences in survival of candidaemia patients can be explained by modulating levels of inflammatory proteins. We identified five genome-wide significant pQTLs that modulate IL-8, MCP-2, MMP-1, and CCL3 in response to C. albicans. In addition, our genetic analysis suggested that GADD45G from rs10114707 locus that reached genome-wide significance could be a potential core gene that regulates a cytokine network upon Candida infection. Last but not least, we observed that a trans-pQTL marked from SNP rs7651677 at chromosome 3 that influences urokinase plasminogen activator (uPA) is strongly associated with patient survival (P survival = 3.52 x 10-5, OR 3). Overall, our genetic analysis showed that genetic variation determines the abundance of circulatory proteins in response to Candida infection.

19.
ACS Chem Neurosci ; 12(18): 3410-3417, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469110

RESUMO

Adenosine receptor (AR) radiotracers for positron emission tomography (PET) have provided knowledge on the in vivo biodistribution of ARs in the central nervous system (CNS), which is of therapeutic interest for various neuropsychiatric disorders. Additionally, radioligands that can image changes in endogenous adenosine levels in different physiological and pathological conditions are still lacking. The binding of known antagonist adenosine A1 receptor (A1R) radiotracer, [11C]MDPX, failed to be inhibited by elevated endogenous adenosine in a rodent PET study. Since most of the known AR PET radiotracers were antagonists, we propose that an A1R agonist radioligand may possess higher sensitivity to measure changes in endogenous adenosine concentration. Herein, we report our latest findings toward the development of a full agonist adenosine A1 radioligand for PET. Based on a 3,5-dicyanopyridine template, 16 new derivatives were designed and synthesized to optimize both binding affinity and functional activity, resulting in two full agonists (compounds 27 and 29) with single-digit nanomolar affinities and good subtype selectivity (A1/A2A selectivity of ∼1000-fold for compound 27 and 29-fold for compound 29). Rapid O-[11C]methylation provided [11C]27 and [11C]29 in high radiochemical yields and radiochemical purity. However, subsequent brain PET imaging in rodents showed poor brain permeability for both radioligands. An in vivo PET study using knockout mice for MDR 1a/a, BCRP, and MRP1 indicated that these compounds might be substrates for brain efflux pumps. In addition, in silico evaluation using multiparameter optimization identified high molecular weight and high polar surface area as the main molecular descriptors responsible for low brain penetration. These results will provide further insight toward development of full agonist adenosine A1 radioligands and also highly potent CNS A1AR drugs.


Assuntos
Proteínas de Neoplasias , Agonistas do Receptor Purinérgico P1 , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adenosina , Animais , Camundongos , Tomografia por Emissão de Pósitrons , Distribuição Tecidual
20.
Environ Res ; 204(Pt A): 111994, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34487696

RESUMO

A heterogeneous electro-Fenton (hetero-EF) system can effectively broaden the applicable pH range, although the decreased electrogeneration efficiency of H2O2 at elevated pH (especially neutral conditions) is unfavorable for the efficient removal of organic pollutants. Herein, a tannic acid-Fe complex derivative-modified carbon felt (TFD@CF) cathode was prepared for hetero-EF treatment of organic pollutants over a wide pH range. Interestingly, the as-prepared hetero-EF cathode could act as a pH regulator that acidified the solution over a wide pH range. As expected, the TFD@CF cathode exhibited excellent hetero-EF activity for the removal of diverse organic pollutants (such as methyl orange, methylene blue, sulfamerazine, bisphenol A and 2,4-dichlorophenoxyacetic acid) at neutral and even alkaline pH (removal efficiency >90 %). A total of 2.98 kWh kg-1 COD-1 with 83.2 % COD removal could be achieved by the TFD@CF cathode for the treatment of actual textile dyeing secondary wastewater. Electrochemical characterizations proved that the TFD@CF cathode had excellent electrochemical properties with improved electron transfer ability and a well-pronounced Fe(III) electroreductive response. Meanwhile, more acidic groups were newly generated during the electrochemical reaction (an increase of 30.1 %), thus dissociating more H+ into solution. The identification of reactive oxygen species suggested that OH and 1O2 could be responsible for the removal of organic pollutants in the TFD@CF EF system. These interesting findings may provide new insights into the design of multifunctional hetero-EF cathodes for the removal of refractory organic pollutants.

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