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Clonal osteoblastic cell lines with CRISPR/Cas9-mediated ablation of Pit1 or Pit2 show enhanced mineralization despite reduced osteogenic gene expression.

Bone 2021 Jun 9;151:116036. Epub 2021 Jun 9.

Department of Bone and Mineral Research, Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization, Izumi, Osaka 594-1101, Japan. Electronic address:

Multiple actions of extracellular Pi on the skeletal cells are likely to be partly mediated by type III sodium/phosphate (Na/Pi) cotransporters Pit1 and Pit2, although the details are not fully understood. In the current study, to determine the roles of Pit1 and Pit2 in osteoblasts, we generated Pit1-knockout (KO) and Pit2-KO osteoblastic cells by applying CRISPR/Cas9 genome editing to an osteoblastic cell line MC3T3-E1 subclone 4. The extracellular Pi level was increased in the Pit1-KO and Pit2-KO clones due to the reduced Pi uptake. Read More

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Perioperative platelet reduction after sutureless or stented valve implantation: results from the PERSIST-AVR controlled randomized trial.

Eur J Cardiothorac Surg 2021 Jun 12. Epub 2021 Jun 12.

Klinikum Nürnberg, Cardiovascular Center, Paracelsus Medical University, Nuremberg, Germany.

Objectives: Platelet count reduction is a common but not fully understood phenomenon after aortic valve replacement (AVR) with bioprosthesis implantation. The aim of the present study was to investigate the occurrence and the clinical impact of platelet count reduction in patients receiving the Perceval bioprosthesis compared to those receiving standard sutured stented bioprosthetic aortic valve in a randomized, controlled AVR study.

Methods: PERceval Sutureless Implant versus STandard Aortic Valve Replacement is a prospective, randomized, adaptive, open-label trial. Read More

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Systemic Jak1 activation causes extrarenal calcitriol production and skeletal alterations provoking stunted growth.

FASEB J 2021 Jul;35(7):e21721

Institute of Physiology, University of Zurich, Zurich, Switzerland.

Mineral homeostasis is regulated by a complex network involving endocrine actions by calcitriol, parathyroid hormone (PTH), and FGF23 on several organs including kidney, intestine, and bone. Alterations of mineral homeostasis are found in chronic kidney disease and other systemic disorders. The interplay between the immune system and the skeletal system is not fully understood, but cytokines play a major role in modulating calcitriol production and function. Read More

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A time-course Raman spectroscopic analysis of spontaneous in vitro microcalcifications in a breast cancer cell line.

Lab Invest 2021 Jun 11. Epub 2021 Jun 11.

School of Physics and Astronomy, University of Exeter, Exeter, UK.

Microcalcifications are early markers of breast cancer and can provide valuable prognostic information to support clinical decision-making. Current detection of calcifications in breast tissue is based on X-ray mammography, which involves the use of ionizing radiation with potentially detrimental effects, or MRI scans, which have limited spatial resolution. Additionally, these techniques are not capable of discriminating between microcalcifications from benign and malignant lesions. Read More

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Neutrophil extracellular traps impair intestinal barrier functions in sepsis by regulating TLR9-mediated endoplasmic reticulum stress pathway.

Cell Death Dis 2021 Jun 11;12(6):606. Epub 2021 Jun 11.

Division of Trauma and Surgical Intensive Care Unit, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, P. R. China.

Increased neutrophil extracellular traps (NETs) formation has been found to be associated with intestinal inflammation, and it has been reported that NETs may drive the progression of gut dysregulation in sepsis. However, the biological function and regulation of NETs in sepsis-induced intestinal barrier dysfunction are not yet fully understood. First, we found that both circulating biomarkers of NETs and local NETs infiltration in the intestine were significantly increased and had positive correlations with markers of enterocyte injury in abdominal sepsis patients. Read More

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Intensive care nurse-family engagement from a global perspective: A qualitative multi-site exploration.

Intensive Crit Care Nurs 2021 Jun 8:103081. Epub 2021 Jun 8.

College of Allied Health and Nursing, Glen Taylor Nursing Institute for Family and Society, Minnesota State University, 360 Wissink Hall and 351 7700 France, Mankato, MN 56001, USA. Electronic address:

Background: Critical illness is distressing for families, and often results in negative effects on family health that influence a family's ability to support their critically ill family member. Although recent attention has been directed at improving care and outcomes for families of critically ill patients, the manner in which nurses engage with families is not fully understood.

Objectives: To describe nurses' perceptions and practices of family engagement in adult intensive care units from a global perspective. Read More

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The Novel FAT4 Activator Jujuboside A Suppresses NSCLC Tumorigenesis by Activating HIPPO Signaling and Inhibiting YAP Nuclear Translocation.

Pharmacol Res 2021 Jun 8:105723. Epub 2021 Jun 8.

Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; State Key Laboratory of Quality Research in Chinese Medicine/ Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau (SAR), China. Electronic address:

FAT atypical cadherin 4 (FAT4) has been identified as a tumor suppressor in lung cancers. However, no agent for lung cancer treatment targeting FAT4 has been used in the clinic. Jujuboside A (JUA) is a major active compound in Semen Ziziphi Spinosae. Read More

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Ochratoxin A induces ERK1/2 phosphorylation-dependent apoptosis through NF-κB/ERK axis in human proximal tubule HK-2 cell line.

Toxicon 2021 Jun 8. Epub 2021 Jun 8.

Bogazici University, Department of Molecular Biology and Genetics, Molecular Toxicology and Cancer Research Laboratory, Bebek-Istanbul, 34342, Turkey; Bogazici University, Center for Life Sciences and Technologies, Bebek-Istanbul, 34342, Turkey. Electronic address:

Ochratoxin A (OTA) is a food contaminant mycotoxin with hazardous effects on human and animal health, primarily affecting the kidneys. OTA's mode of action is not well understood. OTA activates both MAPK/ERK and PI3K/Akt signaling pathways, which play role in apoptosis and cell survival, respectively. Read More

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WFDC2 promotes spasmolytic polypeptide-expressing metaplasia through the upregulation of IL33 in response to injury.

Gastroenterology 2021 Jun 8. Epub 2021 Jun 8.

Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea. Electronic address:

Background & Aims: WAP four-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4 (HE4), is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis using preneoplastic metaplasia models. Read More

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Neuronal post-developmentally acting SAX-7S/L1CAM can function as cleaved fragments to maintain neuronal architecture in C. elegans.

Genetics 2021 Jun 11. Epub 2021 Jun 11.

Université du Québec à Montréal, Department of Biological Sciences, CERMO-FC Research Center, 141 President Kennedy Avenue, Montréal, QC H2X 1Y4, Canada.

Whereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal's growth, maturation processes, the addition of new neurons, body movements, and aging. The C. Read More

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PTEN nuclear translocation enhances neuronal injury after hypoxia-ischemia via modulation of the nuclear factor-κB signaling pathway.

Aging (Albany NY) 2021 Jun 10;13. Epub 2021 Jun 10.

Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan, China.

The occurrence of hypoxia-ischemia (HI) in the developing brain is closely associated with neuronal injury and even death. However, the underlying molecular mechanism is not fully understood. This study was designed to investigate phosphatase and tensin homolog (PTEN) nuclear translocation and its possible role in rat cortical neuronal damage following oxygen-glucose deprivation (OGD) . Read More

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Exploring Internal Medicine Interns' Educational Experiences on Opioid Addiction: A Narrative Analysis.

Health Commun 2021 Jun 11:1-8. Epub 2021 Jun 11.

Department of Communication Studies, Indiana University-Purdue University.

Increased efforts to educate physicians on addiction are crucial based on widespread addiction rates and the ongoing opioid crisis. Physicians in the United States hesitate to adopt medication-assisted treatment (MAT) due to a lack of addiction education. For this study, we used a narrative framework to understand how internal medicine interns (first-year residents) recount their educational experiences on addiction during their medical school education and early residency. Read More

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Activation of human γδ T cells and NK cells by Staphylococcal enterotoxins requires both monocytes and conventional T cells.

J Leukoc Biol 2021 Jun 11. Epub 2021 Jun 11.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

Staphylococcal enterotoxins (SE) pose a great threat to human health due to their ability to bypass antigen presentation and activate large amounts of conventional T cells resulting in a cytokine storm potentially leading to toxic shock syndrome. Unconventional T- and NK cells are also activated by SE but the mechanisms remain poorly understood. In this study, the authors aimed to explore the underlying mechanism behind SE-mediated activation of MAIT-, γδ T-, and NK cells in vitro. Read More

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Optogenetic model reveals cell shape regulation through FAK and Fascin.

J Cell Sci 2021 Jun 11. Epub 2021 Jun 11.

Departments of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Cell shape regulation is important but the mechanisms that govern shape are not fully understood, in part due to limited experimental models where cell shape changes and underlying molecular processes can be rapidly and non-invasively monitored in real time. Here, we use an optogenetic tool to activate RhoA in the middle of mononucleated macrophages to induce contraction, resulting in a side with the nucleus that retains its shape and a non-nucleated side which was unable to maintain its shape and collapsed. In cells overexpressing focal adhesion kinase (FAK), the non-nucleated side exhibited a wide flat morphology and was similar in adhesion area to the nucleated side. Read More

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Longer charged amino acids favor β-strand formation in hairpin peptides.

J Pept Sci 2021 Jun 10:e3333. Epub 2021 Jun 10.

Department of Chemistry, National Taiwan University, Taipei, Taiwan.

Interactions between charged amino acids significantly influence the structure and function of proteins. The encoded charged amino acids Asp, Glu, Arg, and Lys have different number of hydrophobic methylenes linking the backbone to the charged functionality. It remains to be fully understood how does this difference in the number of methylenes affect protein structure stability. Read More

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AnaLysIs of Both sex and device specific factoRs on outcomes in pAtients with non-ischemic cardiomyopathy (BIO-LIBRA): Design and clinical protocol.

Heart Rhythm O2 2020 Dec 10;1(5):376-384. Epub 2020 Nov 10.

Department of Cardiology, University of Washington, Seattle, Washington.

Background: Outcomes of patients with nonischemic cardiomyopathy and low ejection fraction implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D), especially in contemporary, real-life cohorts, are not fully understood.

Objective: We aimed to better characterize outcomes of death and ventricular tachyarrhythmias in patients with nonischemic cardiomyopathy, implanted with an ICD or CRT-D, and specifically assess differences by sex.

Methods: The AnaLysIs of Both Sex and Device Specific FactoRs on Outcomes in PAtients with Non-Ischemic Cardiomyopathy (BIO-LIBRA) study was designed to prospectively assess outcomes of device-treated ventricular tachyarrhythmias and all-cause mortality events in nonischemic cardiomyopathy patients, indicated for an ICD or CRT-D implantation for the primary prevention of sudden cardiac death (SCD), with a specific focus on sex differences. Read More

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December 2020

Development in a Dish- Models of Mammalian Embryonic Development.

Front Cell Dev Biol 2021 25;9:655993. Epub 2021 May 25.

Hubrecht Institute, KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, Netherlands.

Despite decades of research, the complex processes of embryonic development are not fully understood. The study of mammalian development poses particular challenges such as low numbers of embryos, difficulties in culturing embryos , and the time to generate mutant lines. With new approaches we can now address questions that had to remain unanswered in the past. Read More

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COVID-19 Associated Spontaneous Pneumothorax and Pneumopericardium: A Case Report.

Cureus 2021 May 5;13(5):e14861. Epub 2021 May 5.

Critical Care, United General Hospital, Houston, USA.

Novel coronavirus 2019 (COVID-19) has been one of the largest and most devastating global pandemics of our time. There have been several complications of this disease that have also proven to be debilitating and deadly. While primarily affecting the respiratory system, some cases presented with uncommon complications such as pneumopericardium and spontaneous pneumothorax. Read More

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Geranylgeraniol prevents zoledronic acid-mediated reduction of viable mesenchymal stem cells via induction of Rho-dependent YAP activation.

R Soc Open Sci 2021 Jun 9;8(6):202066. Epub 2021 Jun 9.

Biofunctional Materials and Devices Research Group, National Metal and Materials Technology Center, Pathumthani 12120, Thailand.

Long-term use of zoledronic acid (ZA) increases the risk of medication-related osteonecrosis of the jaw (MRONJ). This may be attributed to ZA-mediated reduction of viable mesenchymal stem cells (MSCs). ZA inhibits protein geranylgeranylation, thus suppressing cell viability and proliferation. Read More

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Rapid endogenic rock recycling in magmatic arcs.

Nat Commun 2021 Jun 10;12(1):3533. Epub 2021 Jun 10.

State Key Laboratory for Mineral Deposits Research, School of Earth Sciences and Engineering, Nanjing University, Nanjing, China.

In subduction zones, materials on Earth's surface can be transported to the deep crust or mantle, but the exact mechanisms and the nature of the recycled materials are not fully understood. Here, we report a set of migmatites from western Yangtze Block, China. These migmatites have similar bulk compositions as forearc sediments. Read More

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Stroke care and case fatality in people with and without schizophrenia: a retrospective cohort study.

BMJ Open 2021 Jun 10;11(6):e044766. Epub 2021 Jun 10.

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Background: Schizophrenia is associated with an increased risk of death following stroke; however, the magnitude and underlying reasons for this are not well understood.

Objective: To determine the association between schizophrenia and stroke case fatality, adjusting for baseline characteristics, stroke severity and processes of care.

Design: Retrospective cohort study used linked clinical and administrative databases. Read More

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Carbamoyl Phosphate Synthase Subunit CgCPS1 Is Necessary for Virulence and to Regulate Stress Tolerance in Colletotrichum gloeosporioides.

Plant Pathol J 2021 Jun 1;37(3):232-242. Epub 2021 Jun 1.

Department of Biotechnology, Mirpur University of Science and Technology (MUST), Mirpur 10250, AJK, Pakistan.

Glomerella leaf spot (GLS) is a severe infectious disease of apple whose infective area is growing gradually and thus poses a huge economic threat to the world. Different species of Colletotrichum including Colletotrichum gloeosporioides are responsible for GLS. For efficient GLS control, it is important to understand the mechanism by which the cruciferous crops and C. Read More

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Influence of the different hormonal status changes during their life on fat mass localisation in women: a narrative review.

Arch Physiol Biochem 2021 Jun 10:1-6. Epub 2021 Jun 10.

Université Clermont Auvergne, CRNH, AME2P, Clermont-Ferrand, France.

Context: Independently of the total body fat mass, upper body fat mass deposition is strongly associated with cardiometabolic comorbidities. The mechanisms underlying fat mass localisation are not fully understood, but evidences indicate sex-specific fat mass distribution. Currently, data on women are scarce and the link between hormonal status changes during their life and fat mass distribution is overlooked. Read More

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Fluorescence Anisotropy Decays and Microscale-Volume Viscometry Reveal the Compaction of Ribosome-Bound Nascent Proteins.

J Phys Chem B 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

This work introduces a technology that combines fluorescence anisotropy decay with microscale-volume viscometry to investigate the compaction and dynamics of ribosome-bound nascent proteins. Protein folding in the cell, especially when nascent chains emerge from the ribosomal tunnel, is poorly understood. Previous investigations based on fluorescence anisotropy decay determined that a portion of the ribosome-bound nascent protein apomyoglobin (apoMb) forms a compact structure. Read More

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Palmitic acid induces insulin resistance by a mechanism associated with energy metabolism and calcium entry in neuronal cells.

FASEB J 2021 Jul;35(7):e21712

Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.

Palmitic acid (PA) is a saturated fatty acid whose high consumption has been largely associated with the development of different metabolic alterations, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Particularly in the brain, insulin signaling disruption has been linked to cognitive decline and is considered a risk factor for Alzheimer's disease. Cumulative evidence has demonstrated the participation of PA in the molecular cascade underlying cellular insulin resistance in peripheral tissues, but its role in the development of neuronal insulin resistance and the mechanisms involved are not fully understood. Read More

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Long noncoding RNA CYTOR triggers gastric cancer progression by targeting miR-103/RAB10.

Acta Biochim Biophys Sin (Shanghai) 2021 Jun 10. Epub 2021 Jun 10.

Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110033, China.

Growing evidence has indicated that the long noncoding RNA (lncRNA) CYTOR is involved in the initiation and progression of malignancies, including gastric cancer. Nevertheless, the mechanisms of CYTOR in gastric cancer development are not fully understood. In the present study, we aimed to clarify the association of CYTOR, miR-103, and RAB10 in gastric cancer progression. Read More

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Pigeons as Carriers of Clinically Relevant Multidrug-Resistant Pathogens-A Clinical Case Report and Literature Review.

Front Vet Sci 2021 24;8:664226. Epub 2021 May 24.

Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.

Pigeons are widespread bird species in urban regions ( forma ) and may carry pathogens with zoonotic potential. In recent years, more and more data indicate that these zoonotic pathogens are multidrug resistant. Our results confirmed that global trend. Read More

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Walking is regulated by environmental temperature.

Sci Rep 2021 Jun 9;11(1):12136. Epub 2021 Jun 9.

Taiyo Life Insurance Company, Tokyo, 2-7-1 Nihonbashi, Chuo-Ku, Tokyo, 103-6031, Japan.

The mechanisms that regulate human walking are not fully understood, although there has been substantial research. In our study, we hypothesized that, although walking can be volitionally modified, it is also involuntary and controlled by evolutionary factors, such as the relationship between temperature and movement speed in poikilotherms. This study aimed to determine the effects of environmental temperature on speed, step length, and cadence during unrestrained walking over long periods. Read More

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modelling of interfacial electrochemical properties: beyond implicit solvation limitations.

J Phys Condens Matter 2021 Jun 10;33(30). Epub 2021 Jun 10.

ICGM, Université de Montpellier, CNRS, ENSCM, Montpellier, France.

First-principles calculations are an important tool to investigate the complex processes occurring at solid/liquid interfaces which are at the heart of modern technologies. Currently, capturing the whole electrochemical environment at an interface, including the applied potential and solvation, still remains challenging as it necessitates to couple different approaches whose interactions are not fully understood. In this work, a grand canonical density functional theory approach is coupled with solvation models to investigate the electrochemical interfaces under applied potential. Read More

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The stability of R-spine defines RAF inhibitor resistance: A comprehensive analysis of oncogenic BRAF mutants with in-frame insertion of αC-β4 loop.

Sci Adv 2021 Jun 9;7(24). Epub 2021 Jun 9.

Cancer and Stem Cell Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

Although targeting BRAF mutants with RAF inhibitors has achieved promising outcomes in cancer therapy, drug resistance remains a remarkable challenge, and underlying molecular mechanisms are not fully understood. Here, we characterized a previously unknown group of oncogenic BRAF mutants with in-frame insertions (LLR or VLR) of αC-β4 loop. Using structure modeling and molecular dynamics simulation, we found that these insertions formed a large hydrophobic network that stabilizes R-spine and thus triggers the catalytic activity of BRAF. Read More

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