2-Isopropyl-5-methyl­cyclo­hexyl diphenyl­phospho­namidate

In the title compound, C22H30NO2P, the P atom has an irregular tetra­hedral geometry. In the crystal, mol­ecules are connected by N—H⋯O hydrogen-bonding inter­actions, giving rise to a chain along the b axis. The phenyl ring of the anilino group is twisted by 77.40 (16)° relative to the other phenyl ring. The absolute configuration of phospho­rus is S p

Reprogramming glioblastoma multiforme cells into neurons by protein kinase inhibitors

Abstract Background Reprogramming of cancers into normal-like tissues is an innovative strategy for cancer treatment. Recent reports demonstrate that defined factors can reprogram cancer cells into pluripotent stem cells. Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor in humans. Despite multimodal therapy, the outcome for patients with GBM is still poor. Therefore, developing novel therapeutic strategy is a critical requirement. Methods We have developed a novel reprogramming method that uses a conceptually unique strategy for GBM treatment. We screened a kinase inhibitor library to find which candidate inhibitors under reprogramming condition can reprogram GBM cells into neurons. The induced neurons are identified whether functional and loss of tumorigenicity. Results We have found that mTOR and ROCK kinase inhibitors are sufficient to reprogram GBM cells into neural-like cells and “normal” neurons. The induced neurons expressed neuron-specific proteins, generated action potentials and neurotransmitter receptor-mediated currents. Genome-wide transcriptional analysis showed that the induced neurons had a profile different from GBM cells and were similar to that of control neurons induced by established methods. In vitro and in vivo tumorigenesis assays showed that induced neurons lost their proliferation ability and tumorigenicity. Moreover, reprogramming treatment with ROCK-mTOR inhibitors prevented GBM local recurrence in mice. Conclusion This study indicates that ROCK and mTOR inhibitors-based reprogramming treatment prevents GBM local recurrence. Currently ROCK-mTOR inhibitors are used as anti-tumor drugs in patients, so this reprogramming strategy has significant potential to move rapidly toward clinical trials

N-tert-Butyl O-2-isopropyl-5-methyl­cyclo­hexyl phenyl­phospho­namidate

In the title compound, C20H34NO2P, the P atom has an irregular tetra­hedral environment and exhibits S p chirality. In the crystal, weak inter­molecular N—H⋯O and C—H⋯O hydrogen bonds link the mol­ecules into chains extending in [010]

2-Isopropyl-5-methyl­cyclo­hexyl N-cyclo­hexyl-P-phenyl­phospho­namidate

The title compound, C22H36NO2P, features a P atom bonded to a phenyl ring, a cyclo­hexyl­amine unit and the O atom of a menthyl group. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds connect mol­ecules into a one-dimensional chain in the b direction

catena-Poly[[[diiodidocadmium(II)]-μ-1-(4-pyridylmeth­yl)-1H-benzimidazole] methanol hemisolvate]

In the title coordination polymer, {[CdI2(C13H11N3)]·0.5CH4O}n, each CdII center is four-coordinated by two N-atom donors from two 1-(4-pyridylmeth­yl)-1H-benzimidazole (L) ligands and two iodide anions, forming a tetra­hedral coordination geometry. L ligands bridge adjacent CdII ions, generating two crystallographically independent approximately orthogonal one-dimensional chains. The methanol solvent mol­ecule associates with one of the chains via O—H⋯I inter­actions

A peripherally inserted central vein catheter fractured and slid into the right pulmonary artery: A case report

AbstractCatheter fracture is a rare but serious complication of a peripherally inserted central catheter (PICC). An adolescent patient was sent to Tianjin Medical University General Hospital (Tianjin, China) because the PICC was fractured when removed by a nurse. Chest X-ray showed that the PICC fragment slid into the right pulmonary artery. Through emergency surgery, the remainder of the PICC was successfully retrieved by an interventional operation percutaneously via the right femoral vein. PICC fracture is less common and always without significant discomfort if not found timely, and it may lead to serious complications, such as pulmonary embolism, and even death. Thus, nurses, patients and their family members should pay enough attention to the daily maintenance of PICC and have a deep understanding of the reasons associated with PICC fracture as well as how to prevent it. Interventional operation is minimally invasive, which is a good choice for the removal of intravascular foreign bodies, leading to fewer complications and a good prognosis

Allogeneic hematopoietic stem cell transplantation for acute leukemia with Gilbert's syndrome

Acute leukemia with coexisting Gilbert's syndrome treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rarely reported. Here we described a case whose transaminase levels were almost normal, although transient hyperbilirubinemia repeatedly happened during chemotherapy

R-process beta-decay neutrino flux from binary neutron star merger and collapsar

This study investigates the antineutrinos production by $\beta$-decay of $r$-process nuclei in two astrophysical sites that are capable of producing gamma-ray bursts (GRBs): binary neutron star mergers (BNSMs) and collapsars, which are promising sites for heavy element nucleosynthesis. We employ a simplified method to compute the $\beta$-decay $\bar\nu_e$ energy spectrum and consider two representative thermodynamic trajectories for $r$-process simulations, each with four sets of $Y_e$ distribution. The time evolution of the $\bar\nu_e$ spectrum is derived for both the dynamical ejecta and the disk wind for BNSMs and collapsar outflow, based on approximated mass outflow rates. Our results show that the $\bar\nu_e$ has an average energy of approximately 3 to 9~MeV, with a high energy tail of up to 20 MeV. The $\bar\nu_e$ flux evolution is primarily determined by the outflow duration, and can thus remain large for $\mathcal{O}(10)$~s and $\mathcal{O}(100)$~s for BNSMs and collapsars, respectively. For a single merger or collapsar at 40~Mpc, the $\bar\nu_e$ flux is $\mathcal{O}(10-100)$~cm$^{-2}$~s$^{-1}$, indicating a possible detection horizon up to $0.1-1$~Mpc for Hyper-kamiokande. We also estimate their contributions to the diffuse $\bar\nu_e$ background. Our results suggest that although the flux from BNSMs is roughly 4--5 orders of magnitude lower than that from the regular core-collapse supernovae, those from collapsars can possibly contribute a non-negligible fraction to the total diffuse $\bar\nu_e$ flux at energy $\lesssim 1$~MeV, with a large uncertainty depending on the unknown rate of collapsars capable of hosting the $r$-process.Comment: 13 pages, 7 figure