Dickersonjones6160

This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options.Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled "nanowarming" addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica-coated iron oxide nanoparticles (sIONPs). After cooling at -40 °C min-1 in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min-1 . Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation.Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging-guided SDT in plaque angiogenesis theranostics, termed PFP-HMME@PLGA/MnFe2 O4 -ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe2 O4 ), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid-glycolic acid (PLGA) shells and is conjugated to an anti-VEGFR-2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP-mediated SDT promotes mitochondrial-caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP-mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP-mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP-mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.

Isolated myelosarcoma of infancy is a rare presentation of acute myelogenous leukaemia (AML). Because of its rarity and early onset in infancy underlying genetic predisposition is potentially relevant in disease initiation.

We report an oncologic emergency in an infant with thoracic and intraspinal aleukaemic myeloid sarcoma causing acute myelon compression and lower leg palsy. Whole-exome sequencing of the patient's germline DNA identified a rare PALB2 (OMIM 610355) variant (p.A1079S), which is located in a domain critical for the gene's proper function within the homology-directed repair pathway. In line with potential DNA damage repair defects mediated by the PALB2 deregulation, the patient's fibroblasts showed increased sensitivity towards radiation and DNA intercalating agents.

Therefore, we suggest PALB2 p.A1079S as a pathogenic variant potentially contributing to the here observed patient phenotype.

Therefore, we suggest PALB2 p.A1079S as a pathogenic variant potentially contributing to the here observed patient phenotype.Three-dimensional (3D) micro-and nanostructures have played an important role in topological photonics, microfluidics, acoustic, and mechanical engineering. Incorporating biomimetic geometries into the design of metastructures has created low-density metamaterials with extraordinary physical and photonic properties. However, the use of surface-based biomimetic geometries restricts the freedom to tune the relative density, mechanical strength, and topological phase. The Steiner tree method inspired by the feature of the shortest connection distance in biological neural networks is applied, to create 3D metastructures and, through two-photon nanolithography, neuron-inspired 3D structures with nanoscale features are successfully achieved. Two solutions are presented to the 3D Steiner tree problem the Steiner tree networks (STNs) and the twisted Steiner tree networks (T-STNs). STNs and T-STNs possess a lower density than surface-based metamaterials and that T-STNs have Young's modulus enhanced by 20% than the STNs. Through the analysis of the space groups and symmetries, a topological nontrivial Dirac-like conical dispersion in the T-STNs is predicted, and the results are based on calculations with true predictive power and readily realizable from microwave to optical frequencies. The neuron-inspired 3D metastructures opens a new space for designing low-density metamaterials and topological photonics with extraordinary properties triggered by a twisting degree-of-freedom.The lack of acid stability in the stomach and of temporal stability when moving through the gastrointestinal (GI) tract has made the development of oral magnetic resonance imaging (MRI) contrast agents based on the platform of Gd3+ -complexes problematic.On the other hand, the negative contrast enhancement produced by the T2 -weighted magnetic metal oxide nanoparticles (NPs) often renders the image readout difficult. Biocompatible NPs of the manganese Prussian blue analog K2 Mn3 [FeII (CN)6 ]2 exhibit extremely high stability under the acidic conditions of the gastric juice. Additionally, the high r1 relaxivity, low toxicity, and high temporal stability of such NPs offer great potential for the development of a true T1 -weighted oral contrast agent for MRI of the entire GI tract.Conjugated polymers need to be doped to increase charge carrier density and reach the electrical conductivity necessary for electronic and energy applications. While doping increases carrier density, Coulomb interactions between the dopant molecules and the localized carriers are poorly screened, causing broadening and a heavy tail in the electronic density-of-states (DOS). The authors examine the effects of dopant-induced disorder on two complimentary charge transport properties of semiconducting polymers, the Seebeck coefficient and electrical conductivity, and demonstrate a way to mitigate them. Their simulations, based on a modified Gaussian disorder model with Miller-Abrahams hopping rates, show that dopant-induced broadening of the DOS negatively impacts the Seebeck coefficient versus electrical conductivity trade-off curve. Increasing the dielectric permittivity of the polymer mitigates dopant-carrier Coulomb interactions and improves charge transport, evidenced by simultaneous increases in conductivity and the Seebeck coefficient. They verified this increase experimentally in iodine-doped P3HT and P3HT blended with barium titanate (BaTiO3 ) nanoparticles. The addition of 2% w/w BaTiO3 nanoparticles increased conductivity and Seebeck across a broad range of doping, resulting in a fourfold increase in power factor. Thus, these results show a promising path forward to reduce the dopant-charge carrier Coulomb interactions and mitigate their adverse impact on charge transport.

We evaluated the arginine-depleting enzyme pegargiminase (ADI-PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1-deficient non-squamous non-small cell lung cancer (NSCLC) via a phase 1 dose-expansion trial with exploratory biomarker analysis.

Sixty-seven chemonaïve patients with advanced non-squamous NSCLC were screened, enrolling 21 ASS1-deficient subjects from March 2015 to July 2017 onto weekly pegargiminase (36mg/m

) with Pem (500mg/m

) and Cis (75mg/m

), every 3weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next-generation sequencing and PD-L1 immunohistochemistry.

ADIPemCis was well-tolerated. Plasma arginine and citrulline were differentially modulated; pegargiminase antibodies plateaued by week 10. The disease control rate was 85.7% (n=18/21; 95% CI 63.7%-97%), with a partial response rate of 47.6% (n=10/21; 95% CI 25.7%-70.2%). The medirapies incorporating pegargiminase merit further evaluation in ASS1-deficient and treatment-refractory NSCLC.

To compare adverse events and health-related quality of life in ambulatory home-based chemotherapy with those in inpatient.

Prospective non-randomized observational study.

Participants were divided into two groups according to patients' preference receiving chemotherapy.

Sixty-four participants were enrolled in the inpatient, and 111 were in an ambulatory home-based chemotherapy. The frequency of anaemia, neutropenia and thrombocytopenia was significantly higher in inpatient group than in ambulatory home-based chemotherapy group (p<.001, <.001 and .002, respectively). Nausea, mucositis, and fatigue were more common in ambulatory home-based chemotherapy group than in inpatient group (p<.001, .022, and .005, respectively). Patients in the ambulatory home-based chemotherapy group showed higher social well-being (SWB) scores than inpatient group (coefficient 1.92, 95% confidence interval [CI] 0.65 to 3.19, p .003).

Sixty-four participants were enrolled in the inpatient, and 111 were in an ambulatory home-based chemotherapy. The frequency of anaemia, neutropenia and thrombocytopenia was significantly higher in inpatient group than in ambulatory home-based chemotherapy group (p less then .001, less then .001 and .002, respectively). Nausea, mucositis, and fatigue were more common in ambulatory home-based chemotherapy group than in inpatient group (p less then .001, .022, and .005, respectively). AZD8186 order Patients in the ambulatory home-based chemotherapy group showed higher social well-being (SWB) scores than inpatient group (coefficient 1.92, 95% confidence interval [CI] 0.65 to 3.19, p .003).Combinatorial CpG oligonucleotide (CPG) and chemotherapy drug represent a promising approach to reactivate immune system. However, these two agents possess different physicochemical properties, hindering the application of direct self-assembly of these two cargos into a single nanostructure. Here, a multistage cooperative nanodrug is developed by the direct self-assembly of cis-platinum (CDDP, Pt), l-arginine (l-Arg, R), and CPG (defined as PtR/CPG) for antitumor chemoimmunotherapy. First, the CDDP can induce cell apoptosis. Meanwhile, CDDP also promotes the production of H2 O2 , catalyzing the conversion of l-Arg into nitric oxide (NO). The generated NO decreases the multidrug resistance of cells toward CDDP. Thus, the synergistic effects of CDDP and NO can trigger immunogenic cell death to produce tumor-associated antigens (TAAs). The TAAs and CPG will induce the maturation of dendritic cells (DCs) and enhance antigen presentation ability of DCs. In this way, the PtR/CPG can reverse the immunosuppressive microenvironment, sensitizing tumors to immune checkpoint inhibitors mediated by the programmed death-ligand 1 (PD-L1) antibody.