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https://www.readbyqxmd.com/read/29149720/a-robust-strategy-for-preparation-of-sequential-stimuli-responsive-block-copolymer-prodrugs-via-thiolactone-chemistry-to-overcome-multiple-anticancer-drug-delivery-barriers
#1
Wendong Ke, Wei Yin, Zengshi Zha, Jean Felix Mukerabigwi, Weijian Chen, Yuheng Wang, Chuanxin He, Zhishen Ge
Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of physiological barriers against specific delivery of drugs into tumor cells limit the final therapeutic efficacy. Herein, we report a robust and facile strategy based on thiolactone chemistry to fabricate well-defined BCPs with sequential tumor pH-promoted cellular internalization and intracellular stimuli-responsive drug release...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29149702/an-hplc-tandem-mass-spectrometry-for-quantification-of-et-26-hcl-and-its-major-metabolite-in-plasma-and-application-to-a-pharmacokinetic-study-in-rats
#2
Xu Chen, Wensheng Zhang, Sandy Rios, Miriam B Morkos, Xiaoli Ye, Gen Li, Xuehua Jiang, Zhijun Wang, Ling Wang
ET-26-HCl is a new analog of etomidate, a short-acting anesthetic drug, with less adrenal cortex inhibition. The pharmacokinetics of ET-26-HCl in rats needs to be determined for future clinical trials in human subjects. In order to facilitate the pharmacokinetic study, a liquid chromatography based tandem mass spectrometric (HPLC-MS/MS) method was developed and validated for quantification of ET-26-HCl and its major metabolite, ET-26-acid. These two compounds and gabapentin (internal standard) were extracted using a protein precipitation method with methanol and detected by Multiple Reaction Monitoring of m/z transition of 275...
November 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29149657/the-mechanical-behavior-of-nacre-across-length-scales
#3
Hariprasad Gopalan, Atul H Chokshi
Nacre achieves excellent mechanical properties with a relatively simple hierarchical structure. Analyses suggest that a significant gain in toughness is realized with a modest reduction in strength, with increasing levels of hierarchy. This study probes the role of different hierarchical length scales in governing the strength and modulus of nacre using a combination of bulk compression tests, microindentation and nanoindentation tests. The variability in the measured properties is assessed through Weibull analyses...
October 18, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29149594/conversion-of-bim-bh3-from-activator-to-inhibitor-of-bak-through-structure-based-design
#4
Jason M Brouwer, Ping Lan, Angus D Cowan, Jonathan P Bernardini, Richard W Birkinshaw, Mark F van Delft, Brad E Sleebs, Adeline Y Robin, Ahmad Wardak, Iris K Tan, Boris Reljic, Erinna F Lee, W Douglas Fairlie, Melissa J Call, Brian J Smith, Grant Dewson, Guillaume Lessene, Peter M Colman, Peter E Czabotar
Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149592/dynamics-under-the-telomeric-bridge
#5
Sabrina Pisano, Eric Gilson, Marie-Josèphe Giraud-Panis
In this issue of Molecular Cell, Kim et al. (2017) have studied the structure and organization of the shelterin protein complex protecting telomeres in Schizosaccharomyces pombe and humans and discovered an allosteric structural transition that drives the formation of the shelterin complex and participates in telomere length regulation.
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149566/iedda-reaction-of-molecular-iodine-catalyzed-synthesis-of-1-3-5-triazines-via-functionalization-of-sp-3-c-h-bond-of-acetophenones-with-amidines-an-experimental-investigation-and-dft-study
#6
Abhishek Rajesh Tiwari, Shilpa Raveendra Nath, Kaustubh Ashok Joshi, Bhalchandra Mahadeo Bhanage
The present work reports an inverse electron demand Diels Alder (iEDDA) type reaction to synthesize 1,3,5-trizines from acetophenones and amidines. The use of molecular iodine in catalytic amount facilitates the functionalization of sp3 C-H bond of acetophenones. This is a simple and efficient methodology for the synthesis of 1,3,5-triazines in good to excellent yields under transition metal-free and peroxide-free conditions. The reaction is believed to take place via an in situ iodination-based oxidative elimination of formaldehyde...
November 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29149546/the-photophysical-and-photoacoustic-properties-of-quadrupolar-borondifluoride-curcuminoid-dyes
#7
Stephanie Bellinger, Maryam Hatamimoslehabadi, Seema Bag, Farha Mithila, Jeffrey La, Mathieu Frennete, Samir Laoui, David Szalda, Chandra Yelleswarapu, Jonathan Rochford
The synthesis and characterization of a series of donor-π-acceptor-π-donor (D-A-D) curcuminoid molecules are here presented incorporating π-extended aryl and electron-donating amino terminal functionalization. Computational evaluation shows these molecules possess quadrupolar character with the lowest energy transitions displaying high molar extinction coefficients with broad tunability through manipulation of terminal donating groups. Consistent with their quadrupolar nature, these molecules show varying degrees of solvatochromic behavior in both their absorption and emission spectra which has been analyzed by Lippert-Mataga and Kamlet-Taft analysis...
November 17, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29149539/dynamic-cross-exchange-in-halophosphonium-species-first-direct-observation-of-stereochemical-inversion-in-the-course-of-an-sn2-process
#8
Kirill Nikitin, Elizabeth V Jennings, Sulaiman Al Sulaimi, Yannick Ortin, Declan G Gilheany
The complex fluxional interconversions between, otherwise very similar, phosphonium bromides and chlorides R3PX+X- (R = Alk, Ar, X = Cl or Br) was studied by NMR techniques. Their energy barriers are typically ca. 11 kcal/mol but rise rapidly as bulky groups are attached to phosphorus, revealing the importance of steric factors. In contrast, electronic effects, as measured by Hammett analysis, are modest (rho 1.46) but still clearly indicate negative charge flow towards phosphorus in the transition state. Most significantly, detailed analysis of the exchange pathways unequivocally, and for the first time in any such process, shows that nucleophilic attack of the nucleophilic anion on the tetrahedral centre results in inversion of configuration...
November 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29149476/clinical-parameters-before-and-after-the-transition-to-dialysis
#9
Dugan W Maddux, Len A Usvyat, Terry Ketchersid, Yue Jiao, Tommy C Blanchard, Peter Kotanko, Frank M van der Sande, Jeroen P Kooman, Franklin W Maddux
INTRODUCTION: The transition from pre-dialysis chronic kidney disease (CKD) to post-dialysis start is a critical period associated with high patient mortality and increased hospital admissions. Little is known about the trends of key clinical and laboratory parameters through this time of transition to start dialysis. METHODS: De-identified data including demographics, vital signs, lab results, and eGFR from the Fresenius Medical Care-CKD Registry were analyzed to determine trends in clinical and laboratory parameters through the time of transition from 12 months pre-dialysis start to 12 months post-dialysis start...
November 17, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/29149468/pneumoparotitis-as-a-complication-of-long-term-oronasal-positive-airway-pressure-for-sleep-apnea
#10
Andrew J Goates, Daniel J Lee, Joan E Maley, Phillip C Lee, Henry T Hoffman
BACKGROUND: Parotid swelling is rarely caused by pneumoparotitis from retrograde insufflation of air into Stensen's duct. Previous reports have identified occupational exposures, self-induced habits, exercise, spirometry, and short-term positive pressure airway ventilation as causes of salivary duct insufflation. METHODS: We present 2 cases of pneumoparotitis in patients on long-term oronasal continuous positive airway pressure (CPAP) for obstructive sleep apnea...
November 17, 2017: Head & Neck
https://www.readbyqxmd.com/read/29149465/controlled-sol-gel-transitions-of-a-thermoresponsive-polymer-in-a-photoswitchable-azobenzene-ionic-liquid-as-a-molecular-machine
#11
Masayoshi Watanabe, Caihong Wang, Kei Hashimoto, Ryota Tamate, Hisashi Kokubo
Producing ionic liquids (ILs) that function as molecular machines for macroscopic change is a challenging issue. We report that photoisomerization of an azobenzene IL at the molecular level could evoke a macroscopic response (light-controlled mechanical sol-gel transitions) for ABA triblock copolymer solutions. The A endblocks, poly(2-phenylethyl methacrylate), show a low critical solution temperature in the IL mixture containing azobenzene while the B midblock, poly(methyl methacrylate), is compatible with the mixture...
November 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29149443/migration-of-interneuron-precursors-in-the-nascent-cerebellar-cortex
#12
Annika K Wefers, Christian Haberlandt, Lachezar Surchev, Christian Steinhäuser, Ronald Jabs, Karl Schilling
The cerebellum arguably constitutes one of the best characterized central nervous circuits, and its structure, cellular function, and histogenesis have been described in exceptional quantitative detail. A notable exception to this is the development of its inhibitory interneurons, and in particular the extensive migrations of future basket and stellate cells. Here, we used acute slices from 8-day-old mice to assess the migration of Pax2-EGFP-tagged precursors of these cells en route to the molecular layer during their transit through the nascent cerebellar cortex...
November 17, 2017: Cerebellum
https://www.readbyqxmd.com/read/29149423/structural-and-visible-near%C3%A2-infrared-optical-properties-of-cr-doped-tio2-for-colored-cool-pigments
#13
Le Yuan, Xiaolong Weng, Ming Zhou, Qingyong Zhang, Longjiang Deng
Chromium-doped TiO2 pigments were synthesized via a solid-state reaction method and studied with X-ray diffraction, SEM, XPS, and UV-VIS-NIR reflectance spectroscopy. The incorporation of Cr(3+) accelerates the transition from the anatase phase to the rutile phase and compresses the crystal lattice. Moreover, the particle morphology, energy gap, and reflectance spectrum of Cr-doped TiO2 pigments is affected by the crystal structure and doping concentration. For the rutile samples, some of the Cr(3+) ions are oxidized to Cr(4+) after sintering at a high temperature, which leads to a strong near-infrared absorption band due to the (3)A2 → (3) T1 electric dipole-allowed transitions of Cr(4+)...
November 17, 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/29149295/implementation-of-health-2015-public-health-program-in-finland-a-welfare-state-in-transition
#14
Lauri Kokkinen, Carles Muntaner, Patricia O'Campo, Alix Freiler, Golda Oneka, Ketan Shankardass
Our study sought to examine the implementation of Health 2015 [a public health programme prepared following the principles of Health in All Policies (HiAP)] between 2001 and 2015 in the context of welfare state restructuring. We used data from the realist multiple explanatory case study by HARMONICS, which focused on political factors (processes) that lead to the (un)successful implementation of programmes following the principles of HiAP. We analyzed data-key informant interviews, grey and scholarly literature-from our Finnish case to examine how Health 2015 implementation has been affected by the changing role of the state...
November 14, 2017: Health Promotion International
https://www.readbyqxmd.com/read/29149256/structural-and-immunodiagnostic-characterization-of-synthetic-antigen-b-subunits-from-echinococcus-granulosus-and-their-evaluation-as-target-antigens-for-cyst-viability-assessment
#15
Daniela Pagnozzi, Francesca Tamarozzi, Anna Maria Roggio, Vittorio Tedde, Maria Filippa Addis, Salvatore Pisanu, Gabriella Masu, Cinzia Santucciu, Ambra Vola, Adriano Casulli, Giovanna Masala, Enrico Brunetti, Sergio Uzzau
Background: Several tools have been proposed for serodiagnosis of cystic echinococcosis (CE), but none appears promising for cyst viability assessment. Antigens with stage-specific diagnostic value have been described, but few studies with well-characterized antigens and human sera have been performed. Antigen B (AgB) proteoforms hold promise as markers of viability, due to their differential stage-related expression and immunoreactivity. Methods: Four AgB subunits (AgB1, AgB2, AgB3, AgB4) were synthesized and structurally characterized...
November 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29149233/lighting-up-long-range-charge-transfer-states-by-a-localized-plasmonic-field
#16
Zhen Xie, Sai Duan, Chuan-Kui Wang, Yi Luo
The long-range charge-transfer states in a donor-acceptor system exhibit well separated electron-hole pairs, but are often difficult to achieve by optical means owing to a very small overlap between the wave functions of the donor and acceptor. We have found that the introduction of a spatially confined plasmon can enhance the transition probability to the long-range charge-transfer states as it can effectively break the intrinsic symmetry selection rule imposed on the system. Meanwhile, the intensity borrowed from local excitations could also be selectively promoted, allowing the manipulation of the excited quantum states...
November 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/29149215/longitudinal-survey-of-two-serotine-bat-eptesicus-serotinus-maternity-colonies-exposed-to-eblv-1-european-bat-lyssavirus-type-1-assessment-of-survival-and-serological-status-variations-using-capture-recapture-models
#17
Emmanuelle Robardet, Christophe Borel, Marie Moinet, Dorothée Jouan, Marine Wasniewski, Jacques Barrat, Franck Boué, Elodie Montchâtre-Leroy, Alexandre Servat, Olivier Gimenez, Florence Cliquet, Evelyne Picard-Meyer
This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1) antibodies in serotine bat (Eptesicus serotinus) maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying...
November 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29149103/human-hepatocyte-transplantation-for-liver-disease-current-status-and-future-perspectives
#18
REVIEW
Valeria Iansante, Ragai R Mitry, Céline Filippi, Emer Fitzpatrick, Anil Dhawan
Liver transplantation is the accepted treatment for patients with acute liver failure and liver-based metabolic disorders. However, donor organ shortage and lifelong need for immunosuppression are the main limitations to liver transplantation. In addition, loss of the native liver as target organ for future gene therapy for metabolic disorders limits the futuristic treatment options, resulting in the need for alternative therapeutic strategies. A potential alternative to liver transplantation is allogeneic hepatocyte transplantation...
November 14, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29149039/growth-of-anisotropic-gold-nanoparticle-assemblies-via-liposome-fusion
#19
Kouta Sugikawa, Tatsuya Kadota, Kotaro Matsuo, Kazuma Yasuhara, Atsushi Ikeda
Anisotropic assembly of nanoparticles (NPs) has attracted extensive attention because of the potential applications in materials science, biology, and medicine. However, assembly control (e.g., the number of assembled NPs) has not been adequately studied. Here, the growth of anisotropic gold NP assemblies on a liposome surface is reported. Citrate-coated gold NPs adsorbed on liposome surfaces were assembled in one dimension at temperatures above the phase transition temperature of the lipid bilayer. Growth of the anisotropic assemblies depended on the heating time...
November 17, 2017: Materials
https://www.readbyqxmd.com/read/29148840/resveratrol-induces-mitochondrial-apoptosis-and-inhibits-epithelial-mesenchymal-transition-in-oral-squamous-cell-carcinoma-cells
#20
Seong-Eon Kim, Sang-Hun Shin, Jae-Yeol Lee, Chul-Hoon Kim, In-Kyo Chung, Hae-Mi Kang, Hae-Ryoun Park, Bong-Soo Park, In-Ryoung Kim
OSCC is the most common malignant cancer of the head and neck. EMT is an essential cellular process critical to the morphogenesis and homeostasis of solid tissues. It is also involved in the initial stage of cancer metastasis and invasion in which cells lose epithelial characteristics. While cancer therapy protocols such as surgery, radiation, and chemotherapy are effective and useful, the drug tolerance and toxicity of OSCC patients remain a problem. Resveratrol is mainly produced in red grape skin and exhibits anti-oxidative, anti-inflammatory, anti-proliferative, and anti-cancer properties...
November 17, 2017: Nutrition and Cancer
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