Role of NRP1 in Bladder Cancer Pathogenesis and Progression

Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigated the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. The expression of NRP1 was evaluated using data extracted from GEO and HPA databases and examined in BC cell lines. The effect on proliferation, apoptosis, angiogenesis, migration, and invasion of BC cells were validated after NRP1 knockdown. After identifying differentially expressed genes (DEGs) induced by NRP1 silencing, GO/KEGG and IPA® bioinformatics analyses were performed and specific predicted pathways and targets were confirmed in vitro. Additionally, the co-expressed genes and ceRNA network were predicted using data downloaded from CCLE and TCGA databases, respectively. High expression of NRP1 was observed in BC tissues and cells. NRP1 knockdown promoted apoptosis and suppressed proliferation, angiogenesis, migration, and invasion of BC cells. Additionally, after NRP1 silencing the activity of MAPK signaling and molecular mechanisms of cancer pathways were predicted by KEGG and IPA® pathway analysis and validated using western blot in BC cells. NRP1 knockdown also affected various biological functions, including antiviral response, immune response, cell cycle, proliferation and migration of cells, and neovascularisation. Furthermore, the main upstream molecule of the DEGs induced by NRP1 knockdown may be NUPR1, and NRP1 was also the downstream target of NUPR1 and essential for regulation of FOXP3 expression to activate neovascularisation. DCBLD2 was positively regulated by NRP1, and PPAR signaling was significantly associated with low NRP1 expression. We also found that NRP1 was a predicted target of miR-204, miR-143, miR-145, and miR-195 in BC development. Our data provide evidence for the biological function and molecular aetiology of NRP1 in BC and for the first time demonstrated an association between NRP1 and NUPR1, FOXP3, and DCBLD2. Specifically, downregulation of NRP1 contributes to BC progression, which is associated with activation of MAPK signaling and molecular mechanisms involved in cancer pathways. Therefore, NRP1 may serve as a target for new therapeutic strategies to treat BC and other cancers

Ongoing Spillover of Hantaan and Gou Hantaviruses from Rodents Is Associated with Hemorrhagic Fever with Renal Syndrome (HFRS) in China

Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Thermally tunable slot-coupled dielectric resonator antenna

A thermally tunable slot-coupled dielectric resonator antenna (DRA) has been designed and prepared by placing a thermosensitive ceramic resonator onto the slot. Typical magnetic resonance occurs in the resonator, which is closely related to its dielectric constant. Because the dielectric constant of the ceramic resonator decreases as the temperature increases, the resonance frequency of the proposed DRA increases as the temperature increases. The simulated results are in good agreement with the measured ones, which confirms the thermally tunable behavior. This approach provides a way for designing the frequency tunable antennas

Improving Magnetofection of Magnetic Polyethylenimine Nanoparticles into MG-63 Osteoblasts Using a Novel Uniform Magnetic Field

Abstract This study aimed to improve the magnetofection of MG-63 osteoblasts by integrating the use of a novel uniform magnetic field with low molecular weight polyethylenimine modified superparamagnetic iron oxide nanoparticles (PEI-SPIO-NPs). The excellent characteristics of PEI-SPIO-NPs such as size, zeta potential, the pDNA binding and protective ability were determined to be suitable for gene delivery. The novel uniform magnetic field enabled polyethylenimine-modified superparamagnetic iron oxide nanoparticles/pDNA complexes (PEI-SPIO-NPs/pDNA complexes) to rapidly and uniformly distribute on the surface of MG-63 cells, averting local transfection and decreasing disruption of the membrane caused by the centralization of positively charged PEI-SPIO-NPs, thereby increasing the effective coverage of magnetic gene carriers during transfection, and improving magnetofection efficiency. This innovative uniform magnetic field can be used to determine the optimal amount between PEI-SPIO-NPs and pDNA, as well as screen for the optimal formulation design of magnetic gene carrier under the homogenous conditions. Most importantly, the novel uniform magnetic field facilitates the transfection of PEI-SPIO-NPs/pDNA into osteoblasts, thereby providing a novel approach for the targeted delivery of therapeutic genes to osteosarcoma tissues as well as a reference for the treatment of other tumors