Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth.

By exploiting the self-therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high-grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The biodistribution and toxicity of GNPs administered by intravenous or intraperitoneal injection, both as a single dose or by repeated dosing over two weeks are first assessed; no biochemical or histological toxicity to vital organs is found. Using an orthotopic patient-derived xenograft (PDX) model of HGSOC, the authors then show that GNP treatment robustly inhibits tumor growth.

Experiments with a prototype titanium hot cavity surface ionization source intended for electromagnetic separation of radioactive samarium and other lanthanide elements.

This paper reports experimental results of a prototype titanium surface ionization source. For the first time, a lanthanide ion beam has been produced with a surface ionizer composed completely of titanium metal. Titanium does not readily activate with neutron irradiation.

Computationally modeling mammalian succinate dehydrogenase kinetics identifies the origins and primary determinants of ROS production.

Succinate dehydrogenase (SDH) is an inner mitochondrial membrane protein complex that links the Krebs cycle to the electron transport system. It can produce significant amounts of superoxide ([Formula: see text]) and hydrogen peroxide (HO); however, the precise mechanisms are unknown. This fact hinders the development of next-generation antioxidant therapies targeting mitochondria.

Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome.

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create "auroliposomes," which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems-commercial transfection agents, conventional liposomes, and auroliposomes.

Polymersomes Eradicating Intracellular Bacteria.

Mononuclear phagocytes such as monocytes, tissue-specific macrophages, and dendritic cells are primary actors in both innate and adaptive immunity. These professional phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favoring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis (TB), which is the most pandemic and one of the deadliest diseases, with one-third of the world's population infected and an average of 1.

Harvesting V at the National Superconducting Cyclotron Laboratory.

As part of an effort to develop aqueous isotope harvesting techniques at radioactive beam facilities, V and a cocktail of primary- and secondary-beam ions created by the fragmentation reaction of a 160 MeV/nucleon Ni beam were stopped in an aqueous target cell. After collection, V was separated from the mixture of beam ions using cation-exchange chromatography. The extraction efficiency from the aqueous solution was (47.

Isotope harvesting with Hollow Fiber Supported Liquid Membrane (HFSLM).

The Facility for Rare Isotope Beams (FRIB) will generate many unique isotopes of scientific interest which are retained in the primary beam dump. This work uses Hollow Fiber Supported Liquid Membrane (HFSLM) for extraction of ultra-trace concentrations of short-lived radioisotopes from the large solution volumes present in the primary beam dump loop. Part per trillion levels of V were successfully recovered from an aqueous solution spiked with predicted concentrations of chemically similar species, with an extraction efficiency of 71% in 60 min.

Precocious neuronal differentiation and disrupted oxygen responses in Kabuki syndrome.

Chromatin modifiers act to coordinate gene expression changes critical to neuronal differentiation from neural stem/progenitor cells (NSPCs). Lysine-specific methyltransferase 2D (KMT2D) encodes a histone methyltransferase that promotes transcriptional activation and is frequently mutated in cancers and in the majority (>70%) of patients diagnosed with the congenital, multisystem intellectual disability disorder Kabuki syndrome 1 (KS1). Critical roles for KMT2D are established in various non-neural tissues, but the effects of KMT2D loss in brain cell development have not been described.

Gold Nanoparticle Transforms Activated Cancer-Associated Fibroblasts to Quiescence.

Activated cancer-associated fibroblasts (CAFs) play a major role in the poor outcome in many diseases including pancreatic cancer. Normally quiescent with high lipid content and low proliferative capacity, CAFs receiving cues from cancer cells in the tumor microenvironment become activated and transformed into a lipid-deprived and highly proliferative myofibroblast type phenotype. Therefore, reversal of activated fibroblasts to the quiescence state is an important area of investigation that may help the therapeutic management of a number of diseases including pancreatic cancer.

Boron-neutron Capture on Activated Carbon for Hydrogen Storage.

This work investigates the effects of neutron irradiation on nitrogen and hydrogen adsorption in boron-doped activated carbon. Boron-neutron capture generates an energetic lithium nucleus, helium nucleus, and gamma photons, which can alter the surface and structure of pores in activated carbon. The defects introduced by fission tracks are modeled assuming the slit-shaped pores geometry.

The surprisingly large neutron capture cross-section of Zr.

The probability that a nucleus will absorb a neutron-the neutron capture cross-section-is important to many areas of nuclear science, including stellar nucleosynthesis, reactor performance, nuclear medicine and defence applications. Although neutron capture cross-sections have been measured for most stable nuclei, fewer results exist for radioactive isotopes, and statistical-model predictions typically have large uncertainties. There are almost no nuclear data for neutron-induced reactions of the radioactive nucleus Zr, despite its importance as a diagnostic for nuclear security.

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes.

Background: Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours.

Self-healing effects in a semi-ordered liquid for stable electronic conversion of high-energy radiation.

Radiation damage in solid-state semiconductors has, until now, placed strict limitations on the acceptable decay energies of radioisotopes in radiovoltaic cells. Relegation to low-energy beta-emitting isotopes has minimized the power output from these devices and limited the technology's ability to deliver greater energy densities and longer lifetimes than conventional batteries. We demonstrate the self-healing abilities of a liquid-phase semiconducting alloy which can withstand high-energy alpha radiation.

Demonstration of a novel Xp22.2 microdeletion as the cause of familial extreme skewing of X-inactivation utilizing case-parent trio SNP microarray analysis.

Background: We report a kindred referred for molecular investigation of severe hemophilia A in a young female in which extremely skewed X-inactivation was observed in both the proband and her clinically normal mother.

Methods: Bidirectional Sanger sequencing of all F8 gene coding regions and exon/intron boundaries was undertaken. Methylation-sensitive restriction enzymes were utilized to investigate skewed X-inactivation using both a classical human androgen receptor (HUMARA) assay, and a novel method targeting differential methylation patterns in multiple informative X-chromosome SNPs.

Variation in Activity State, Axonal Projection, and Position Define the Transcriptional Identity of Individual Neocortical Projection Neurons.

Single-cell RNA sequencing has generated catalogs of transcriptionally defined neuronal subtypes of the brain. However, the cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state.

Synthesis and targeting of gold-coated Lu-containing lanthanide phosphate nanoparticles-A potential theranostic agent for pulmonary metastatic disease.

Targeted radiotherapies maximize cytotoxicity to cancer cells. In this work, we describe the synthesis, characterization, and biodistribution of antibody conjugated gold-coated lanthanide phosphate nanoparticles containing Lu. [Lu]LuGd(PO)@Au@PEG@Ab nanoparticles combine the radiation resistance of crystalline lanthanide phosphate for stability, the magnetic properties of gadolinium for facile separations, and a gold coating that can be readily functionalized for the attachment of targeting moieties.

Cadmium exposure and endometrial cancer risk: A large midwestern U.S. population-based case-control study.

Estrogen-mimicking chemicals, such as cadmium, may be associated with increased susceptibility to hormone-dependent cancers, though supporting data are sparse, particularly for endometrial cancer. The Health and Environmental Exposure Research (HEER) study worked with the Arkansas Central Cancer Registry, Iowa Cancer Registry and Missouri Cancer Registry to obtain names of women diagnosed with endometrial cancer who were willing to be contacted for participation in our case control study. Voter registration lists from Iowa and Missouri were used to randomly select similarly aged women as represented in the case population.

Measurement of Pu in keratinous materials: A potential non-invasive bioassay for monitoring human exposure.

The use of hair, toenail, and fingernail as non-invasive monitors of occupational and environmental exposure to Pu are reported. Volunteers from US national laboratories and individuals with suspected environmental exposure to Pu were recruited to participate in the study. The exposure history of cases was assessed using a short questionnaire.

Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting.

To gain a better understanding of the role of somatic mutations in olaparib response, next-generation sequencing (NGS) of BRCA1 and BRCA2 was performed as part of a planned retrospective analysis of tumors from a randomized, double-blind, Phase II trial (Study 19; D0810C00019; NCT00753545) in 265 patients with platinum-sensitive high-grade serous ovarian cancer. BRCA1/2 loss-of-function mutations were found in 55% (114/209) of tumors, were mutually exclusive, and demonstrated high concordance with Sanger-sequenced germline mutations in matched blood samples, confirming the accuracy (97%) of tumor BRCA1/2 NGS testing. Additionally, NGS identified somatic mutations absent from germline testing in 10% (20/209) of the patients.

In vivo transport of three radioactive [F]-fluorinated deoxysucrose analogs by the maize sucrose transporter ZmSUT1.

Sucrose transporter (SUT) proteins translocate sucrose across cell membranes; however, mechanistic aspects of sucrose binding by SUTs are not well resolved. Specific hydroxyl groups in sucrose participate in hydrogen bonding with SUT proteins. We previously reported that substituting a radioactive fluorine-18 [F] at the C-6' position within the fructosyl moiety of sucrose did not affect sucrose transport by the maize (Zea mays) ZmSUT1 protein.

Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery.

Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally.

Long-Term Responders on Olaparib Maintenance in High-Grade Serous Ovarian Cancer: Clinical and Molecular Characterization.

Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted.

Ionic Liquid-Assisted Synthesis of Nanoscale (MoS)(SnO) on Reduced Graphene Oxide for the Electrocatalytic Hydrogen Evolution Reaction.

Layered transition metal dichalcogenides (TMDs) have attracted increased attention due to their enhanced hydrogen evolution reaction (HER) performance. More specifically, ternary TMD nanohybrids, such as MoSSe or bimetallic sulfides, have arisen as promising electrocatalysts compared to MoS and MoSe due to their electronic, morphologic, and size tunabilities. Herein, we report the successful synthesis of few-layered MoS/rGO, SnS/rGO, and (MoS)(SnO)/rGO nanohybrids anchored on reduced graphene oxide (rGO) through a facile hydrothermal reaction in the presence of ionic liquids as stabilizing, delayering agents.