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https://www.readbyqxmd.com/read/28644482/one-thousand-fold-enhancement-of-high-field-liquid-nuclear-magnetic-resonance-signals-at-room-temperature
#1
Guoquan Liu, Marcel Levien, Niels Karschin, Giacomo Parigi, Claudio Luchinat, Marina Bennati
Nuclear magnetic resonance (NMR) is a fundamental spectroscopic technique for the study of biological systems and materials, molecular imaging and the analysis of small molecules. It detects interactions at very low energies and is thus non-invasive and applicable to a variety of targets, including animals and humans. However, one of its most severe limitations is its low sensitivity, which stems from the small interaction energies involved. Here, we report that dynamic nuclear polarization in liquid solution and at room temperature can enhance the NMR signal of (13)C nuclei by up to three orders of magnitude at magnetic fields of ∼3 T...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28639395/spatiotemporally-controllable-peptide-based-nanoassembly-in-single-living-cells-for-a-biological-self-portrait
#2
Yuanyuan Zhao, Xu Zhang, Zhipeng Li, Shuaidong Huo, Ke Zhang, Juntao Gao, Hao Wang, Xing-Jie Liang
Simultaneous precise localization and activity evaluation of a biomolecule in a single living cell is through an enzyme-specific signal-amplification process, which involves the localized, site-specific self-assembly, and activation of a presignaling molecule. The inactive presignaling tetraphenylethylene (TPE)-peptide derivative, TPE-YpYY, is nondetectable and highly biocompatible and these small molecules rapidly diffuse into living cells. Upon safely arriving at an active site, and accessing the catalytic pocket of an enzyme, TPE-YpYY immediately and quantitatively accumulates in situ in response to enzymatic activity, forms an enzyme anchor TPE-YYY nanoassembly, displays aggregation-induced emission behavior, and finally lights up the active enzyme, indicating its activity, and allowing its status in living cells to be tracked...
June 22, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28638783/recent-advances-of-activatable-molecular-probes-based-on-semiconducting-polymer-nanoparticles-in-sensing-and-imaging
#3
REVIEW
Yan Lyu, Kanyi Pu
Molecular probes that change their signals in response to the target of interest have a critical role in fundamental biology and medicine. Semiconducting polymer nanoparticles (SPNs) have recently emerged as a new generation of purely organic photonic nanoagents with desirable properties for biological applications. In particular, tunable optical properties of SPNs allow them to be developed into photoluminescence, chemiluminescence, and photoacoustic probes, wherein SPNs usually serve as the energy donor and internal reference for luminescence and photoacoustic probes, respectively...
June 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28638478/-177-lu-labeled-phosphoramidate-based-psma-inhibitors-the-effect-of-an-albumin-binder-on-biodistribution-and-therapeutic-efficacy-in-prostate-tumor-bearing-mice
#4
Cindy J Choy, Xiaoxi Ling, Jonathan J Geruntho, Sophia K Beyer, Joseph D Latoche, Beatrice Langton-Webster, Carolyn J Anderson, Clifford E Berkman
Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a (177)Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401)...
2017: Theranostics
https://www.readbyqxmd.com/read/28638467/dual-responsive-molecular-probe-for-tumor-targeted-imaging-and-photodynamic-therapy
#5
Xiaoqing Meng, Yueting Yang, Lihua Zhou, Li Zhang, Yalin Lv, Sanpeng Li, Yayun Wu, Mingbin Zheng, Wenjun Li, Guanhui Gao, Guanjun Deng, Tao Jiang, Dapeng Ni, Ping Gong, Lintao Cai
The precision oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging and therapeutics. In this study, a first small-molecule theranostic probe, RhoSSCy is constructed by conjugating 5'-carboxyrhodamines (Rho) and heptamethine cyanine IR765 (Cy) using a reducible disulfide linker and pH tunable amino-group to realize thiols/pH dual sensing. In vitro experiments verify that RhoSSCy is highly sensitive for quantitative analysis and imaging intracellular pH gradient and biothiols...
2017: Theranostics
https://www.readbyqxmd.com/read/28635963/single-molecule-analysis-of-steroid-receptor-and-cofactor-action-in-living-cells
#6
Ville Paakinaho, Diego M Presman, David A Ball, Thomas A Johnson, R Louis Schiltz, Peter Levitt, Davide Mazza, Tatsuya Morisaki, Tatiana S Karpova, Gordon L Hager
Population-based assays have been employed extensively to investigate the interactions of transcription factors (TFs) with chromatin and are often interpreted in terms of static and sequential binding. However, fluorescence microscopy techniques reveal a more dynamic binding behaviour of TFs in live cells. Here we analyse the strengths and limitations of in vivo single-molecule tracking and performed a comprehensive analysis on the intranuclear dwell times of four steroid receptors and a number of known cofactors...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#7
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28631478/drying-affects-the-fiber-network-in-low-molecular-weight-hydrogels
#8
Laura L E Mears, Emily R Draper, Ana M Castilla, Hao Su, Zhuola Zhuola, Bart Dietrich, Michael Nolan, Gregory N Smith, James Doutch, Sarah E Rogers, Riaz Akhtar, Honggang Cui, Dave J Adams
Low molecular weight gels are formed by the self-assembly of a suitable small molecule gelator into a three-dimensional network of fibrous structures. The gel properties are determined by the fiber structures, the number and type of cross-links and the distribution of the fibers and cross-links in space. Probing these structures and cross-links is difficult. Many reports rely on microscopy of dried gels (xerogels), where the solvent is removed prior to imaging. The assumption is made that this has little effect on the structures, but it is not clear that this assumption is always (or ever) valid...
June 20, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28627888/investigation-of-drug-induced-hepatotoxicity-and-its-remediation-pathway-with-reaction-based-fluorescent-probes
#9
Dan Cheng, Wang Xu, Lin Yuan, Xiao-Bing Zhang
Drug-induced liver injury (DILI) is considered a serious problem related to public health, due to its unpredictability and acute response. The level of peroxynitrite (ONOO-) generated in liver has long been regarded as a biomarker for the prediction and measurement of DILI. Herein we present two reaction based fluorescent probes (Naph-ONOO- and Rhod-ONOO-) for ONOO- through a novel and universally applicable mechanism: ONOO- mediated deprotection of -keto caged fluorophores. Among them, Rhod-ONOO- can selectively accumulate and react in mitochondria, one of the main sources of ONOO-, with a substantial lower nano-molar sensitivity of 43 nM...
June 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28621571/targeted-nanotechnologies-for-cancer-intervention-a-patent-review-2010-2016
#10
Priyamvada Pradeep, Pradeep Kumar, Yahya E Choonara, Viness Pillay
In recent years, several active targeting nanostrategies have been patented for application in cancer theranostics. The versatility of nanostructures in terms of composition, manufacturability, functionalization, and matrix formation make them ideal for carrying large dose of bioactive contents, high density of targeting ligands on their surface, efficient delivery to the site of interest, and capable of forming multicomponent platforms. Areas covered: The patents were classified into polymeric and non-polymeric nanostructures and their applicability in addressing the targeting paradigm related to cancer intervention was explored...
June 22, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28620662/hexagonal-boron-nitride-nanosheets-as-a-multifunctional-background-free-matrix-to-detect-small-molecules-and-complicated-samples-by-maldi-mass-spectrometry
#11
Jianing Wang, Jie Sun, Jiyun Wang, Huihui Liu, Jinjuan Xue, Zongxiu Nie
Here we report the innovation of using hexagonal boron nitride (h-BN) nanosheets as the first background-free matrix among the full laser pulse energy range for the analysis and imaging of small molecule metabolites and as an adsorbent for the enrichment of samples. Due to its totally free background and high efficiency as an adsorbent and matrix, h-BN has promising prospects in metabolomics, MALDI imaging, and environmental analysis.
June 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28618012/metabolomic-signature-of-brain-cancer
#12
Renu Pandey, Laura Caflisch, Alessia Lodi, Andrew J Brenner, Stefano Tiziani
Despite advances in surgery and adjuvant therapy, brain tumours represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumours, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which characterizes the phenotype of an individual. This emerging "omics" science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumour biology...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28617496/a-reconstructed-anatase-001-1-%C3%A3-4-surface-and-its-reactivity
#13
Meiling Xu, Sheng Wang, Hui Wang
An anatase TiO2(001) surface has shown great potential as an ideal and powerful photocatalyst due to its chemical stability, nontoxicity, and high reactivity. However, the fundamental atomic structure of the reconstructed anatase (001)-(1 × 4) surface is still under debate, which greatly impedes further exploration of its chemical activity. Herein, the anatase (001)-(1 × 4) surface reconstruction and the photocatalytic reactivity have been extensively studied using an effective surface structure searching method in combination with the first-principles calculations...
June 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28612067/stretch-dependent-changes-in-molecular-conformation-in-fibronectin-nanofibers
#14
John M Szymanski, Emily N Sevcik, Kairui Zhang, Adam W Feinberg
Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that plays an important role in a wide range of biological processes including embryonic development, wound healing, and fibrosis. Recent evidence has demonstrated that FN is mechanosensitive, where the application of force induces conformational changes within the FN molecule to expose otherwise cryptic binding domains. However, it has proven technically challenging to dynamically monitor how the nanostructure of FN fibers changes as a result of force-induced extension, due in part to the inherent complexity of FN networks within tissue and cell-generated extracellular matrix (ECM)...
June 14, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28611099/cell-based-bioluminescent-assay-for-monitoring-the-interaction-between-pcsk9-and-the-ldl-receptor
#15
Sarah J Duellman, Thomas Machleidt, James J Cali, Jolanta Vidugiriene
Monitoring the expression of cell-surface receptors, their interaction with extracellular ligands, and their fate upon ligand binding is important for understanding receptor function and developing new therapies. We describe a cell-based method that utilizes bioluminescent protein complementation technology to interrogate binding of a cellular receptor with its extracellular protein ligand, specifically LDLR and PCSK9. Purified, full-length tagged PCSK9 is added to assay wells containing cells that stably express LDLR with an extracellular complementary tag...
June 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28604617/targeted-magnetic-nanotheranostics-of-cancer
#16
REVIEW
Irina Belyanina, Olga Kolovskaya, Sergey Zamay, Ana Gargaun, Tatiana Zamay, Anna Kichkailo
Current advances in targeted magnetic nanotheranostics are summarized in this review. Unique structural, optical, electronic and thermal properties of magnetic materials in nanometer scale are attractive in the field of biomedicine. Magnetic nanoparticles functionalized with therapeutic molecules, ligands for targeted delivery, fluorescent and other chemical agents can be used for cancer diagnostic and therapeutic purposes. High selectivity, small size, and low immunogenicity of synthetic nucleic acid aptamers make them attractive delivery agents for therapeutic purposes...
June 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28600491/development-and-evaluation-of-18-f-irs-for-molecular-imaging-mutant-egf-receptors-in-nsclc
#17
Yan Song, Zunyu Xiao, Kai Wang, Xiance Wang, Chongqing Zhang, Fang Fang, Xilin Sun, Baozhong Shen
To prepare and evaluate a new radiotracer (18)F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of (18)F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging. Ex vivo biodistribution assays were performed to quantify the accumulation of (18)F-IRS in vivo. We also performed (18)F-IRS PET/CT imaging of three patients with NSCLC...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28598856/glucocerebrosidase-mutations-in-parkinson-disease
#18
Grace O'Regan, Ruth-Mary deSouza, Roberta Balestrino, A H Schapira
Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD. In patients with a known GBA mutation, it is possible to monitor for prodromal signs of PD...
June 7, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28594000/synthesis-and-preliminary-pet-imaging-of-11-c-and-18-f-isotopologues-of-the-ros1-alk-inhibitor-lorlatinib
#19
Thomas Lee Collier, Marc D Normandin, Nickeisha A Stephenson, Eli Livni, Steven H Liang, Dustin W Wooten, Shadi A Esfahani, Michael G Stabin, Umar Mahmood, Jianqing Chen, Wei Wang, Kevin Maresca, Rikki N Waterhouse, Georges El Fakhri, Paul Richardson, Neil Vasdev
Lorlatinib (PF-06463922) is a next-generation small-molecule inhibitor of the orphan receptor tyrosine kinase c-ros oncogene 1 (ROS1), which has a kinase domain that is physiologically related to anaplastic lymphoma kinase (ALK), and is undergoing Phase I/II clinical trial investigations for non-small cell lung cancers. An early goal is to measure the concentrations of this drug in brain tumour lesions of lung cancer patients, as penetration of the blood-brain barrier is important for optimal therapeutic outcomes...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28591846/visualization-of-conformational-variability-in-the-domains-of-long-single-stranded-rna-molecules
#20
Jamie L Gilmore, Aiko Yoshida, James A Hejna, Kunio Takeyasu
We demonstrate an application of atomic force microscopy (AFM) for the structural analysis of long single-stranded RNA (>1 kb), focusing on 28S ribosomal RNA (rRNA). Generally, optimization of the conditions required to obtain three-dimensional (3D) structures of long RNA molecules is a challenging or nearly impossible process. In this study, we overcome these limitations by developing a method using AFM imaging combined with automated, MATLAB-based image analysis algorithms for extracting information about the domain organization of single RNA molecules...
June 7, 2017: Nucleic Acids Research
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