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Quantitative characterization of human oncogene promoter G-quadruplex DNA-ligand interactions using a combination of mass spectrometry and capillary electrophoresis.

Electrophoresis 2021 May 14. Epub 2021 May 14.

Department of Chemistry, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

Human c-KIT oncogene is known to regulate cell growth and proliferation, and thus, acts as a probable target in the treatment of gastrointestinal tumors (GIST). To identify small molecule ligands which can specifically bind with the G-quadruplex (G4) in the c-KIT promoter region as potential antitumor agents, we propose the combination of electrospray ionization mass spectrometry (ESI-MS), capillary electrophoresis frontal analysis (CE-FA), and Taylor dispersion analysis (TDA) to accurately investigate the G4/ligands binding properties. First, ESI-MS was used for initial screening of natural products (NPs). Read More

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A small-molecule Psora-4 acts as a caloric restriction mimetic to promote longevity in C. elegans.

Geroscience 2021 May 14. Epub 2021 May 14.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117608, Singapore.

In populations around the world, the fraction of humans aged 65 and above is increasing at an unprecedented rate. Aging is the main risk factor for the most important degenerative diseases and this demographic shift poses significant social, economic, and medical challenges. Pharmacological interventions directly targeting mechanisms of aging are an emerging strategy to delay or prevent age-dependent diseases. Read More

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Chiral-spin rotation of non-collinear antiferromagnet by spin-orbit torque.

Nat Mater 2021 May 13. Epub 2021 May 13.

Laboratory for Nanoelectronics and Spintronics, Research Institute of Electrical Communication, Tohoku University, Aoba-ku, Sendai, Japan.

Electrical manipulation of magnetic materials by current-induced spin torque constitutes the basis of spintronics. Here, we show an unconventional response to spin-orbit torque of a non-collinear antiferromagnet MnSn, which has attracted attention owing to its large anomalous Hall effect despite a vanishingly small net magnetization. In epitaxial heavy-metal/MnSn heterostructures, we observe a characteristic fluctuation of the Hall resistance under the application of electric current. Read More

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Sevoflurane excites nociceptive sensory neurons by inhibiting K conductances in rats.

Neurosci Lett 2021 May 10;756:135951. Epub 2021 May 10.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, 41940, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu, 41940, Republic of Korea. Electronic address:

Sevoflurane, which is preferentially used as a day-case anesthetic based on its low blood solubility, acts on the central nervous system and exerts analgesic effects. However, it still remains unknown whether sevoflurane affects the excitability of nociceptive sensory neurons. Therefore, we conducted this study to examine the effects of sevoflurane on the excitability of small-sized dorsal root ganglion (DRG) neurons of rats using the whole-cell patch-clamp technique. Read More

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Mechanism of MRX inhibition by Rif2 at telomeres.

Nat Commun 2021 May 12;12(1):2763. Epub 2021 May 12.

Université de Paris, Université Paris-Saclay, Inserm, CEA, Institut de Biologie François Jacob, iRCM, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France.

Specific proteins present at telomeres ensure chromosome end stability, in large part through unknown mechanisms. In this work, we address how the Saccharomyces cerevisiae ORC-related Rif2 protein protects telomere. We show that the small N-terminal Rif2 BAT motif (Blocks Addition of Telomeres) previously known to limit telomere elongation and Tel1 activity is also sufficient to block NHEJ and 5' end resection. Read More

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Avasopasem manganese synergizes with hypofractionated radiation to ablate tumors through the generation of hydrogen peroxide.

Sci Transl Med 2021 May;13(593)

Division of Molecular Radiation Biology, Department of Radiation Oncology, and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Avasopasem manganese (AVA or GC4419), a selective superoxide dismutase mimetic, is in a phase 3 clinical trial (NCT03689712) as a mitigator of radiation-induced mucositis in head and neck cancer based on its superoxide scavenging activity. We tested whether AVA synergized with radiation via the generation of hydrogen peroxide, the product of superoxide dismutation, to target tumor cells in preclinical xenograft models of non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, and pancreatic ductal adenocarcinoma. Treatment synergy with AVA and high dose per fraction radiation occurred when mice were given AVA once before tumor irradiation and further increased when AVA was given before and for 4 days after radiation, supporting a role for oxidative metabolism. Read More

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Celebrating 60 Years of Accomplishments of the Armed Forces Radiobiology Research Institute1.

Radiat Res 2021 May 12. Epub 2021 May 12.

Scientific Research Department.

Chartered by the U.S. Congress in 1961, the Armed Forces Radiobiology Research Institute (AFRRI) is a Joint Department of Defense (DoD) entity with the mission of carrying out the Medical Radiological Defense Research Program in support of our military forces around the globe. Read More

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Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2.

ACS Infect Dis 2021 May 12. Epub 2021 May 12.

Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and human ACE2 (hACE2), which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than that with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable/less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound library focused around the chemical space of organic dyes. Read More

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Spatial Control of Charge Doping in n-Type Topological Insulators.

Nano Lett 2021 May 12. Epub 2021 May 12.

Materials Science Institute of Madrid (ICMM), Spanish Scientific Research Council (CSIC), and the CSIC Associated Unit "MATINÉE", between the Institute of Materials Science of the Valencia University (ICMUV) and the ICMM, Cantoblanco, Madrid E-28049, Spain.

Spatially controlling the Fermi level of topological insulators and keeping their electronic states stable are indispensable processes to put this material into practical use for semiconductor spintronics devices. So far, however, such a method has not been established yet. Here we show a novel method for doping a hole into n-type topological insulators BiX (X= Se, Te) that overcomes the shortcomings of the previous reported methods. Read More

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Controls on Interspecies Electron Transport and Size Limitation of Anaerobically Methane-Oxidizing Microbial Consortia.

mBio 2021 May 11;12(3). Epub 2021 May 11.

Department of Marine Sciences, University of Georgia, Athens, Georgia, USA.

About 382 Tg yr of methane rising through the seafloor is oxidized anaerobically (W. S. Reeburgh, Chem Rev 107:486-513, 2007, https://doi. Read More

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Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials.

Eur J Cancer 2021 May 8;151:115-125. Epub 2021 May 8.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: Immuno-oncology (IO)-based therapies have been approved based on randomised clinical trials, yet a significant proportion of real-world patients are not represented in these trials. We sought to compare the outcomes of trial-ineligible vs. -eligible patients with advanced solid tumours treated with first-line (1L) IO therapy. Read More

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A Plant Leaf-Mimetic Membrane with Controllable Gas Permeation for Efficient Preservation of Perishable Products.

ACS Nano 2021 May 10. Epub 2021 May 10.

Research Institute of Resources Insects, Chinese Academy of Forestry, 650233 Kunming, China.

About one-third of the world's food is lost and wasted each year, along with excessive carbon emission, disposals, and other environmental issues. The rotting of perishable products like fruits and vegetables accounts for the largest percentage of food waste due to their short shelf life. The storage atmosphere (HO, O, CO) acts as a key role in the preservation process and could regulate plants' physiological metabolism and microbial growth. Read More

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A possible way to prevent the progression of bone lesions in multiple myeloma via Src-homology-region-2-domain-containing-phosphatase-1 activation.

J Cell Biochem 2021 May 10. Epub 2021 May 10.

Department of Molecular Immunology and Inflammation, Research Institute National Center for Global Health and Medicine, Tokyo, Japan.

On the basis of our recent findings, in which multiple receptor-mediated mast cell functions are regulated via a common signaling cascade, we posit that the formation and functioning of osteoclasts are also controlled by a similar common mechanism. These cells are derived from the same granulocyte/monocyte progenitors and share multiple receptors except those that are cell-specific. In both types of cells, all known receptors reside in lipid rafts, form multiprotein complexes with recruited signaling molecules, and are internalized upon receptor engagement. Read More

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TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis.

Front Oncol 2021 21;11:676202. Epub 2021 Apr 21.

School of Laboratory Medicine/Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu, China.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. Read More

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Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma.

Sci Rep 2021 May 7;11(1):9785. Epub 2021 May 7.

Diagnostic and Research Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria.

In the last two decades, various therapies have been introduced for lung carcinoma patients, including tyrosine-kinase inhibitors for different mutations. While some of them are specific to specific tumor types, others, like NTRK1-3 fusions, are found in various solid tumors. The occurrence of an NTRK1,2 or 3 fusion acts as a biomarker for efficient treatment with NTRK inhibitors, irrespectively of the tumor type. Read More

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Application of a sub-0.1-mm implantable mote for in vivo real-time wireless temperature sensing.

Sci Adv 2021 May 7;7(19). Epub 2021 May 7.

Department of Electrical Engineering, Columbia University, New York, NY 10027, USA.

There has been increasing interest in wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. Here, we present such an implant that uses a conventional ultrasound imager for wireless powering and data communication and acts as a probe for real-time temperature sensing, including the monitoring of body temperature and temperature changes resulting from therapeutic application of ultrasound. The sub-0. Read More

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Population dynamics of microbial cross-feeding are determined by co-localization probabilities and cooperation-independent cheater growth.

ISME J 2021 May 5. Epub 2021 May 5.

Systems Biology Lab, Amsterdam Institute of Molecular and Life Sciences, VU University Amsterdam, de Boelelaan 1108, Amsterdam, The Netherlands.

As natural selection acts on individual organisms the evolution of costly cooperation between microorganisms is an intriguing phenomenon. Introduction of spatial structure to privatize exchanged molecules can explain the evolution of cooperation. However, in many natural systems cells can also grow to low cell concentrations in the absence of these exchanged molecules, thus showing "cooperation-independent background growth". Read More

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Collapse-induced phase transitions in binary interfacial microgel monolayers.

Soft Matter 2021 May;17(17):4504-4516

Institute of Particle Technology, Friedrich-Alexander University Erlangen-Nürnberg, Cauerstrasse 4, 91058 Erlangen, Germany.

Microgels, consisting of a swollen polymer network, exhibit a more complex self-assembly behavior compared to incompressible colloidal particles, because of their ability to deform at a liquid interface or collapse upon compression. Here, we investigate the collective phase behavior of two-dimensional binary mixtures of microgels confined at the air/water interface. We use stimuli-responsive poly(N-isopropylacrylamide) microgels with different crosslinking densities, and therefore different morphologies at the interface. Read More

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JAS-GAN: Generative Adversarial Network Based Joint Atrium and Scar Segmentation on Unbalanced Atrial Targets.

IEEE J Biomed Health Inform 2021 May 4;PP. Epub 2021 May 4.

Automated and accurate segmentation of the left atrium (LA) and atrial scars from late gadolinium-enhanced cardiac magnetic resonance (LGE CMR) images are in high demand for quantifying atrial scars. The previous quantification of atrial scars relies on a two-phase segmentation for LA and atrial scars due to their large volume difference (unbalanced atrial targets). In this paper, we propose an inter-cascade generative adversarial network, namely JAS-GAN, to segment the unbalanced atrial targets from LGE CMR images automatically and accurately in an end-to-end way. Read More

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Six-Degree-of-Freedom Steerable Visible-Light-Driven Microsubmarines Using Water as a Fuel: Application for Explosives Decontamination.

Small 2021 May 4:e2100294. Epub 2021 May 4.

Center for the Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology, Technická 5, Prague, 16628, Czech Republic.

Micro/nanomotors are capable of a wide variety of tasks related, i.e., to biomedical or environmental applications. Read More

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Defining key residues of the Swi1 prion domain in prion formation and maintenance.

Mol Cell Biol 2021 May 3. Epub 2021 May 3.

Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

Prions are self-perpetuating, alternative protein conformations associated with neurological diseases and normal cellular functions. contains many endogenous prions - providing a powerful system to study prionization. Previously, we demonstrated that Swi1, a component of the SWI/SNF chromatin-remodeling complex, can form the prion []. Read More

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Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer.

Front Pharmacol 2021 15;12:621181. Epub 2021 Apr 15.

Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide, yet effective treatment remains a clinical challenge. Guaiazulene (GYZ), a cosmetic color additive, has previously been characterized as a potential antitumor agent due to observed anticancer effects. However, the efficacy of GYZ in the treatment of NSCLC and the involved molecular mechanisms remain largely unknown. Read More

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Casp8 Acts Through A20 to Inhibit PD-L1 Expression: The Mechanism and Its Implication in Immunotherapy.

Cancer Sci 2021 May 2. Epub 2021 May 2.

Department of Abdominal Oncology, West China Hospital, Sichuan University, Cancer Center, Sichuan Province, Chengdu, China.

Immunotherapy targeting the PD-L1/PD-1 pathway is a novel type of clinical cancer treatment, but only small subsets of patients can benefit from it because of multiple factors. PD-L1/PD-1 expression is a biomarker for predicting the efficacy of anti-PD-L1/PD-1 therapy, which highlights the importance of understanding the regulatory mechanisms of PD-L1 expression in cancer cells. Casp8 is an apical caspase protease involved in mediating cell apoptosis, but it also has multiple nonapoptotic functions. Read More

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Role of MicroRNAs, Aptamers in Neuroinflammation and Neurodegenerative Disorders.

Cell Mol Neurobiol 2021 May 1. Epub 2021 May 1.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, Hyderabad, Telangana, 500037, India.

Exploring the microRNAs and aptamers for their therapeutic role as biological drugs has expanded the horizon of its applicability against various human diseases, explicitly targeting the genetic materials. RNA-based therapeutics are widely being explored for the treatment and diagnosis of multiple diseases, including neurodegenerative disorders (NDD). Latter includes microRNA, aptamers, ribozymes, and small interfering RNAs (siRNAs), which control the gene expression mainly at the transcriptional strata. Read More

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[Problems of updating the procedures for the provision of medical care used in diseases of the ear and mastoid, throat and nose].

D O Roshchin

Vestn Otorinolaringol 2021 ;86(2):99-103

National Research Institute of Public Health named after N.A. Semashko of the Ministry of Education and Science of Russia, Moscow, Russia.

The procedures for the provision of medical care in otorhinolaryngology and audiology-otorhinolaryngology contain a large number of requirements. The actualization of the orders has not been carried out for a long time, which is due to the lack of methodological formalized approaches for the formation of hypotheses regarding expedient changes. The article proposes an analysis of the results of state control, which will allow the formation of specific proposals for assessment by experts in the framework of the process of updating the procedures for the provision of medical care. Read More

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What do Germans really think about health-nudges?

BMC Public Health 2021 Apr 29;21(1):821. Epub 2021 Apr 29.

Heidelberg University, Institute of Medical Biometry and Informatics, Heidelberg, Germany.

Background: In recent years, policymakers have increasingly used behaviourally informed policies, including 'nudges'. They have been implemented to produce desirable social outcomes such as healthier eating and physical activity. In Germany, a small research team at the Federal Chancellery acts as the central unit to promote the introduction of nudges in the design of public life. Read More

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Impaired Expression of Cytoplasmic Actins Leads to Chromosomal Instability of MDA-MB-231 Basal-Like Mammary Gland Cancer Cell Line.

Molecules 2021 Apr 8;26(8). Epub 2021 Apr 8.

N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia.

We have shown previously that two cytoplasmic actin isoforms play different roles in neoplastic cell transformation. Namely, β-cytoplasmic actin acts as a tumor suppressor, whereas γ-cytoplasmic actin enhances malignant features of tumor cells. The distinct participation of each cytoplasmic actin in the cell cycle driving was also observed. Read More

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Chiral Triphenylacetic Acid Esters: Residual Stereoisomerism and Solid-State Variability of Molecular Architectures.

J Org Chem 2021 May 28;86(9):6433-6448. Epub 2021 Apr 28.

Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61 614 Poznań, Poland.

We have proven the usability and versatility of chiral triphenylacetic acid esters, compounds of high structural diversity, as chirality-sensing stereodynamic probes and as molecular tectons in crystal engineering. The low energy barrier to stereoisomer interconversion has been exploited to sense the chirality of an alkyl substituent in the esters. The structural information are cascaded from the permanently chiral alcohol (inducer) to the stereodynamic chromophoric probe through cooperative interactions. Read More

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LncRNA SUMO1P3 acts as a prognostic biomarker and promotes hepatocellular carcinoma growth and metastasis.

Aging (Albany NY) 2021 Apr 26;13. Epub 2021 Apr 26.

Medical College, Henan University of Science and Technology, Luoyang 471003, Henan, China.

Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers, including hepatocellular carcinoma (HCC). However, the biological functions of lncRNA small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) and the underlying mechanisms remain unclear. In this study, we revealed that SUMO1P3 expression was enhanced in HCC tissues and cell lines, positively associating with tumor size and number, poor differentiation, lymphatic and distant metastasis, TNM stage, and poor prognosis in HCC patients. Read More

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Expression of Nectin-4 in Bladder Urothelial Carcinoma, in Morphologic Variants, and Nonurothelial Histotypes.

Appl Immunohistochem Mol Morphol 2021 Apr 23. Epub 2021 Apr 23.

Departments of Urology Oncolocy Pathology, Johns Hopkins University School of Medicine Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD.

The antibody-drug conjugate enfortumab-vedotin acts by targeting nectin-4, a protein that is nearly ubiquitously expressed in conventional urothelial cancer. However, expression of nectin-4 in morphologic variants of urothelial carcinoma and nonurothelial histotypes was unknown. Immunohistochemistry for nectin-4 using was performed on 169 patients including 83 with nonmuscle invasive bladder cancer and 86 patients with muscle invasive bladder cancer. Read More

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