Bengtsonsharpe3359
Selective endothelial cell adhesion was performed at 37 °C using GGGREDV as an affinity peptide. Smooth muscle cells and fibroblasts did not adhere to the copolymer brush. Adhered human umbilical vein endothelial cells (HUVECs) were successfully recovered by reducing the temperature to 20 °C. Based on the properties of the copolymer brush, HUVECs could be purified using a mixture of cells simply by changing the temperature. These results demonstrated that the prepared copolymer brush with cell affinity peptides could be a useful cell separation tool because the cells could be separated with specificity and without cell modification using a simple procedure.Nonlinear optical characterization of nanostructured layered transition metal dichalcogenides (LTMDs) is of fundamental interest for basic knowledge and applied purposes. In particular, second-order optical nonlinearities are the basis for second harmonic generation as well as sum or difference frequency generation and have been studied in some 2D TMDs, especially in those with a semiconducting character. Here we report, for the first time, on the second-order nonlinearity of the semi-metallic ZrTe2 monolayer in acetonitrile suspension (concentration of 4.9 × 1010 particles per cm3), synthesized via a modified redox exfoliation method and characterized using the Hyper-Rayleigh scattering technique in the nanosecond regime. The orientation-averaged first-hyperpolarizability was found to be β(2ω) = (7.0 ± 0.3) × 10-24 esu per ZrTe2 monolayer flake, the largest reported so far. Polarization-resolved measurements were performed in the monolayer suspension and indicate the dipolar origin of the generated incoherent second harmonic wave.High temperature proton exchange membrane fuel cells (HT-PEMFCs) are one type of promising energy device with the advantages of fast reaction kinetics (high energy efficiency), high tolerance to fuel/air impurities, simple plate design, and better heat and water management. PP2 cost They have been expected to be the next generation of PEMFCs specifically for application in hydrogen-fueled automobile vehicles and combined heat and power (CHP) systems. However, their high-cost and low durability interposed by the insufficient performance of key materials such as electrocatalysts and membranes at high temperature operation are still the challenges hindering the technology's practical applications. link2 To develop high performance HT-PEMFCs, worldwide researchers have been focusing on exploring new materials and the related technologies by developing novel synthesis methods and innovative assembly techniques, understanding degradation mechanisms, and creating mitigation strategies with special emphasis on catalysts for oxygen reduction reaction, proton exchange membranes and bipolar plates. In this paper, the state-of-the-art development of HT-PEMFC key materials, components and device assembly along with degradation mechanisms, mitigation strategies, and HT-PEMFC based CHP systems is comprehensively reviewed. In order to facilitate further research and development of HT-PEMFCs toward practical applications, the existing challenges are also discussed and several future research directions are proposed in this paper.The presence of a hemibond in the local solvation structure of the aqueous hydroxyl radical has long been debated, as its appearance in ab initio simulations based on density functional theory is sensitive to self-interaction error (favoring a two-center, three-electron hemibond) but also to finite-size effects. link3 Simulations reported here use a mixed quantum mechanics/molecular mechanics (QM/MM) framework in a very large periodic simulation cell, in order to avoid finite-size artifacts and to facilitate testing of various density functionals, in order to probe the effects of delocalization error. The preponderance of hemibonded structures predicted by generalized gradient approximations persists in simulations using the hybrid functionals B3LYP and PBE0, but is reduced to a minor population if the fraction of exact exchange is increased to 50%. The hemibonded population is also small in simulations employing the long-range corrected functional LRC-ωPBE. Electronic spectra are computed using time-dependent density functional theory, and from these calculations emerges a consensus picture in which hemibonded configurations play an outsized role in the absorption spectrum, even when present as a minority species. An intense 1b2(H2O) → 2pπ(˙OH) charge-transfer transition in hemibonded configurations of the radical proves to be responsible for an absorption feature at 230 nm that is strongly shifted with respect to the gas-phase absorption at 307 nm, but this intense feature is substantially diminished in aqueous geometries where the hemibond is absent. Although not yet sufficient to quantitatively establish the population of hemibonded ˙OH(aq), these simulations do suggest that its presence is revealed by the strongly shifted ultraviolet absorption spectrum of the aqueous radical.The rapid spread of SARS-CoV-2 (COVID-19) since December 2019 forced Intensive Care Units to face high numbers of patients admitted simultaneously with limited resources. COVID-19 critically ill patients, especially those on mechanical ventilators, demand special attention as they can develop potential complications with critical hemodynamic and respiratory consequences. Point of Care Ultrasound (POCUS) might have important roles in assessing the critically ill SARS-CoV-2 patient. Mostly, lung ultrasound has been presented as having a role in diagnosis and monitoring, but airway examination and hemodynamic evaluation are of interest also. We propose an A.B.C. POCUS approach focusing on A-airway (orotracheal intubation), B-breathing (interstitial syn-dromes, pneumothorax, atelectasis, pneumonia), and C-circulation (cardiac function, pulmonary embolism, volume status, deep veins thrombosis). This A.B.C. approach has emerged during ICU care for 22 adult COVID-19 critically ill patients, along with the analysis of recent papers describing ultrasound in COVID-19 patients including the use of ultrasound that is currently applied in the management of the general critically ill population. This A.B.C- POCUS algorithm parallels the well-established clinical A.B.C. algorithms. There are few extensive ultrasonographic studies in COVID-19 critically ill patients up to now, but techniques extrapolated from non-COVID studies seem reasonable even though comparative studies are not available yet.
12b80 combines doxorubicin bound to a bone targeting hydroxybisphosphonate vector using a pH-sensitive linker, designed to specifically trigger doxorubicin release in an acidic bone tumor microenvironment. This phase I study aimed to determine the safety and toxicity profiles of 12b80 in dogs with naturally occurring osteosarcoma, with the objective to translate findings from dogs to humans.
Ten client-owned dogs with osteosarcoma were enrolled in an accelerated dose-titration design followed by 3 + 3 design. Dogs received three cycles of 12b80 intravenous injection at 4 mg/kg (
= 1), 6 mg/kg (
= 2), 8 mg/kg (
= 3), and 10 mg/kg (
= 4). Endpoints included safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity (DLT).
The MTD of 12b80 was 8 mg/kg (i.e., equivalent dose of doxorubicin of 110 mg/m
, range 93-126). Most adverse events included grade ≤ 2 gastrointestinal disorders and hypersensitivity reactions. No hematological or cardiac DLT were observed at any dose tested.
In dogs, 12b80 is overall well tolerated and expends the MTD of doxorubicin up to four times the standard dose of 30 mg/m
. These results demonstrate the potential therapeutic benefit of 12b80 in canine and human osteosarcoma.
In dogs, 12b80 is overall well tolerated and expends the MTD of doxorubicin up to four times the standard dose of 30 mg/m2. These results demonstrate the potential therapeutic benefit of 12b80 in canine and human osteosarcoma.The involvement of non-coding RNAs (ncRNAs) in cellular physiology and disease pathogenesis is becoming increasingly relevant in recent years specifically in cancer research. Breast cancer (BC) has become a health concern and accounts for most of the cancer-related incidences and mortalities reported amongst females. In spite of the presence of promising tools for BC therapy, the mortality rate of metastatic BC cases is still high. Therefore, the genomic exploration of the BC subtype and the use of ncRNAs for possible regulation is pivotal. The expression and prognostic values of AURKA gene were assessed by Oncomine, GEPIA, KM-plotter, and bc-GenExMiner v4.4, respectively. Associated proteins and functional enrichment were evaluated by Cytoscape and DAVID databases. Additionally, molecular docking approach was employed to investigate the regulatory role of hsa-miR-32-3p assisted argonaute (AGO) protein of AURKA gene in BC. AURKA gene was highly expressed in patients with BC relative to normal counterpart and significantly correlated with poor survival. The docking result suggested that AURKA could be regulated by hsa-miR-32-3p as confirmed by the reported binding energy and specific interactions. The study gives some insights into role of AURKA and its regulation by microRNAs through AGO protein. It also provides exciting opportunities for cancer therapeutic intervention.COVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. In serum-deprived and stimulated cells treated with remdesivir and MEKi we observed correlations between pRB, pERK, and ACE2 expression further supporting role of proliferative state and MAPK pathway in ACE2 regulation. We show elevated cytokines in COVID-19-(+) patient plasma (N = 9) versus control (N = 11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1α, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed MEKi stimulation of NK-cell killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope infected human bronchial epithelial cells, small airway epithelial cells, or lung cancer cells and MEKi suppressed infectivity of the pseudovirus. We show a drug class-effect with MEKi to stimulate NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection to allow immune responses and antiviral agents to control disease progression.[This corrects the article DOI 10.18632/oncotarget.27558.].Hyaluronic Acid-binding protein 4 (HABP4) is a regulatory protein of 57 kDa that is functionally involved in transcription regulation and RNA metabolism and shows several characteristics common to oncoproteins or tumor suppressors, including altered expression in cancer tissues, nucleus/cytoplasm shuttling, intrinsic lack of protein structure, complex interactomes and post translational modifications. Its gene has been found in a region on chromosome 9q22.3-31, which contains SNP haplotypes occurring in individuals with a high risk for familial colon cancer. To test a possible role of HABP4 in tumorigenesis we generated knockout mice by the CRISPR/Cas9 method and treated the animals with azoxymethane (AOM)/dextran sodium sulfate (DSS) for induction of colon tumors. HABP4-/- mice, compared to wild type mice, had more and larger tumors, and expressed more of the proliferation marker proteins Cyclin-D1, CDK4 and PCNA. Furthermore, the cells of the bottom of the colon crypts in the HABP4-/- mice divided more rapidly.