The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation

Predictors of intra-abdominal coagulopathic hemorrhage after living donor liver transplantation

AbstractBackgroundResults of preoperative conventional coagulation assays are a poor predictor of hemorrhage after liver transplantation. In this study, we evaluated the factors that are predictive of intra-abdominal coagulopathic hemorrhage after living donor liver transplantation surgery.MethodsDuring the period from January 2009 to December 2012, 118 adults underwent living donor liver transplantation (LDLT) in our institution. Of those patients, 18 (15.3%) developed intra-abdominal coagulopathic hemorrhage (n = 7) or hemorrhage due to non-coagulopathic causes (n = 11) that required emergency medical, radiological, or surgical intervention within the first month after LDLT. Possible predictors of postoperative coagulopathic hemorrhage included donor-related factors, age, body mass index, MELD score, INR value, intra-operative blood transfusion, graft/recipient weight ratio, anhepatic phase, cold ischemia time, operative time, APACHE II score, onset of re-bleeding, and hemoglobin levels during rebleeding episodes.ResultsThere were no differences in any of the variables between the two groups (coagulopathic and noncoagulopathic hemorrhage) except for cold ischemia time. We found that cold ischemia time was significantly longer in patients with postoperative coagulopathic hemorrhage (160.50 ± 45.02 min) than in patients with hemorrhage due to non-coagulopathic causes (113.55 ± 29.31 min; P = 0.027).ConclusionProlonged cold ischemia time is associated with postoperative intra-abdominal coagulopathic hemorrhage in patients after LDLT. It is, therefore, necessary to shorten the cold ischemia time in order to reduce the risk of postoperative intra-abdominal hemorrhage due to coagulopathic causes

Oxidized-monolayer Tunneling Barrier for Strong Fermi-level Depinning in Layered InSe Transistors

In 2D-semiconductor-based field-effect transistors and optoelectronic devices, metal-semiconductor junctions are one of the crucial factors determining device performance. The Fermi-level (FL) pinning effect, which commonly caused by interfacial gap states, severely limits the tunability of junction characteristics, including barrier height and contact resistance. A tunneling contact scheme has been suggested to address the FL pinning issue in metal-2D-semiconductor junctions, whereas the experimental realization is still elusive. Here, we show that an oxidized-monolayer-enabled tunneling barrier can realize a pronounced FL depinning in indium selenide (InSe) transistors, exhibiting a large pinning factor of 0.5 and a highly modulated Schottky barrier height. The FL depinning can be attributed to the suppression of metal- and disorder-induced gap states as a result of the high-quality tunneling contacts. Structural characterizations indicate uniform and atomically thin surface oxidation layer inherent from nature of van der Waals materials and atomically sharp oxide-2D-semiconductor interfaces. Moreover, by effectively lowering the Schottky barrier height, we achieve an electron mobility of 2160 cm$^2$/Vs and a contact barrier of 65 meV in two-terminal InSe transistors. The realization of strong FL depinning in high-mobility InSe transistors with the oxidized monolayer presents a viable strategy to exploit layered semiconductors in contact engineering for advanced electronics and optoelectronics

IMPAD1 functions as mitochondrial electron transport inhibitor that prevents ROS production and promotes lung cancer metastasis through the AMPK-Notch1-HEY1 pathway

The tumor microenvironment (TME) and metabolic reprogramming have been implicated in cancer development and progression. However, the link between TME, metabolism, and cancer progression in lung cancer is unclear. In the present study, we identified IMPAD1 from the conditioned medium of highly invasive CL1-5. High expression of IMPAD1 was associated with a poorer clinical phenotype in lung cancer patients, with reduced survival and increased lymph node metastasis. Knockdown of IMPAD1 significantly inhibited migration/invasion abilities and metastasis in vitro and in vivo. Upregulation of IMPAD1 and subsequent accumulation of AMP in cells increased the pAMPK, leading to Notch1 and HEY1 upregulation. As AMP is an ADORA1 agonist, treatment with ADORA1 inhibitor reduced the expression of pAMPK and HEY1 expression in IMPAD1-overexpressing cells. IMPAD1 caused mitochondria dysfunction by inhibiting mitochondrial Complex I activity, which reduced mitochondrial ROS levels and activated the AMPK-HEY1 pathway. Collectively this study supports the multipotent role of IMPAD1 in promotion of lung cancer metastasis by simultaneously increasing AMP levels, inhibition of Complex I activity to decrease ROS levels, thereby activating AMPK-Notch1-HEY1 signaling, and providing an alternative metabolic pathway in energy stress conditions

Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction

Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, and COX-2 expression in human BCC cells. TAMs also aggregate near COX-2 expressing BCC tumor nests. We hypothesize that TAMs might activate COX-2 in BCC cells and subsequently increase their invasion and angiogenesis. TAMs are a kind of M2 macrophage derived from macrophages exposed to Th2 cytokines. M2-polarized macrophages derived from peripheral blood monocytes were cocultured with BCC cells without direct contact. Coculture with the M2 macrophages induced COX-2-dependent invasion and angiogenesis of BCC cells. Human THP-1 cell line cells, after treated with phorbol myristate acetate (PMA), differentiated to macrophages with M2 functional profiles. Coculture with PMA-treated THP-1 macrophages induced COX-2-dependent release of matrix metalloproteinase-9 and subsequent increased invasion of BCC cells. Macrophages also induced COX-2-dependent secretion of basic fibroblast growth factor and vascular endothelial growth factor-A, and increased angiogenesis in BCC cells

Nesting-driven antiferromagnetic order in Kondo lattice CePd5Al2

We investigated the electronic structure of the antiferromagnetic Kondo lattice CePd5Al2 using high-resolution angle-resolved photoemission spectroscopy. The experimentally determined band structure of the conduction electrons is predominated by the Pd 4d character. It contains multiple hole and electron Fermi pockets, in good agreement with density functional theory calculations. The Fermi surface is folded over Q0 = (0, 0, 1), manifested by Fermi surface reconstruction and band folding. Our results suggest that Fermi surface nesting drives the formation of antiferromagnetic order in CePd5Al2.Comment: 6 pages,3 figur

Case report: Heterogenous SMARCA4-deficient thoracic non-small cell lung carcinoma with various responses to nivolumab

SMARCA4-deficient non-small cell carcinoma is an aggressive neoplasm with poor outcome. Several studies have highlighted its immunochemistry, pathophysiology, and underlying mechanisms, but studies of its definite treatment are few. Here, we report on a 69-year-old male with heterogenous pathological presentations of SMARCA4-deficient non-small cell carcinoma. He initially presented with neck lymphadenopathies. Immunohistochemistry staining and genomic profiling confirmed the diagnosis of SMARCA4-deficient non-small cell carcinoma. The patient responded well to immune checkpoint inhibitors with nivolumab. However, new lesions with various pathological presentations and various responses to nivolumab appeared during the treatment course. The patient survived more than 3 years from the initial diagnosis. This case shows the efficacy of nivolumab to treat SMARCA4-deficient non-small cell lung carcinoma

A Holistic Perspective on the Dynamics of G035.39-00.33 : The Interplay between Gas and Magnetic Fields

Magnetic field plays a crucial role in shaping molecular clouds and regulating star formation, yet the complete information on the magnetic field is not well constrained owing to the limitations in observations. We study the magnetic field in the massive infrared dark cloud G035.39-00.33 from dust continuum polarization observations at 850 mu m with SCUBA-2/POL-2 at JCMT for the first time. The magnetic field tends to be perpendicular to the densest part of the main filament (F-M), whereas it has a less defined relative orientation in the rest of the structure, where it tends to be parallel to some diffuse regions. A mean plane-of-the-sky magnetic field strength of similar to 50 mu G for F-M is obtained using the Davis-Chandrasekhar-Fermi method. Based on (CO)-C-13 (1-0) line observations, we suggest a formation scenario of F-M due to large-scale (similar to 10 pc) cloud-cloud collision. Using additional NH3 line data, we estimate that F-M will be gravitationally unstable if it is only supported by thermal pressure and turbulence. The northern part of F-M, however, can be stabilized by a modest additional support from the local magnetic field. The middle and southern parts of F-M are likely unstable even if the magnetic field support is taken into account. We claim that the clumps in F-M may be supported by turbulence and magnetic fields against gravitational collapse. Finally, we identified for the first time a massive (similar to 200 M-circle dot, collapsing starless clump candidate, "c8," in G035.39-00.33. The magnetic field surrounding "c8" is likely pinched, hinting at an accretion flow along the filament.Peer reviewe