Strong spin-orbit coupling fosters exotic electronic states such as topological insulators and superconductors, but the combination of strong spin-orbit and strong electron-electron interactions is ...just beginning to be understood. Central to this emerging area are the 5d transition metal iridium oxides. Here, in the pyrochlore iridate Pr2Ir2O7, we identify a non-trivial state with a single-point Fermi node protected by cubic and time-reversal symmetries, using a combination of angle-resolved photoemission spectroscopy and first-principles calculations. Owing to its quadratic dispersion, the unique coincidence of four degenerate states at the Fermi energy, and strong Coulomb interactions, non-Fermi liquid behaviour is predicted, for which we observe some evidence. Our discovery implies that Pr2Ir2O7 is a parent state that can be manipulated to produce other strongly correlated topological phases, such as topological Mott insulator, Weyl semimetal, and quantum spin and anomalous Hall states.
Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the ...early detection of recurrence in human colorectal cancer (CRC).
Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT-PCR.
Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P<0.001).
Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.
The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting ...RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to-mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth. RAGE knockdown with multiple independent shRNAs in breast cancer cells led to decreased transwell invasion and soft agar colony formation, without affecting proliferation. In vivo, targeting RAGE shRNA knockdown in human and mouse breast cancer cells, decreased orthotopic tumor growth, reduced tumor angiogenesis and recruitment of inflammatory cells, and markedly decreased metastasis to the lung and liver in multiple xenograft and syngeneic mouse models. To test the non-tumor cell microenvironment role of RAGE, we performed syngeneic studies with orthotopically injected breast cancer cells in wild-type and RAGE-knockout C57BL6 mice. RAGE-knockout mice displayed striking impairment of tumor cell growth compared with wild-type mice, along with decreased mitogen-activated protein kinase signaling, tumor angiogenesis and inflammatory cell recruitment. To test the combined inhibition of RAGE in both tumor cell-intrinsic and non-tumor cells of the microenvironment, we performed in vivo treatment of xenografted tumors with FPS-ZM1 (1 mg/kg, two times per week). Compared with vehicle, FPS-ZM1 inhibited primary tumor growth, inhibited tumor angiogenesis and inflammatory cell recruitment and, most importantly, prevented metastasis to the lung and liver. These data demonstrate that RAGE drives tumor progression and metastasis through distinct tumor cell-intrinsic and -extrinsic mechanisms, and may represent a novel and therapeutically viable approach for treating metastatic cancers.
Background
Few larger studies have estimated the incidence of incisional hernia (IH) after abdominal surgery.
Methods
Patients who had abdominal surgery between November 2009 and February 2011 were ...included in the study. The incidence rate and risk factors for IH were monitored for at least 180 days.
Results
A total of 4305 consecutive patients were registered. Of these, 378 were excluded because of failure to complete follow‐up and 3927 patients were analysed. IH was diagnosed in 318 patients. The estimated incidence rates for IH were 5·2 per cent at 12 months and 10·3 per cent at 24 months. In multivariable analysis, wound classification III and IV (hazard ratio (HR) 2·26, 95 per cent confidence interval 1·52 to 3·35), body mass index of 25 kg/m2 or higher (HR 1·76, 1·35 to 2·30), midline incision (HR 1·74, 1·28 to 2·38), incisional surgical‐site infection (I‐SSI) (HR 1·68, 1·24 to 2·28), preoperative chemotherapy (HR 1·61, 1·08 to 2·37), blood transfusion (HR 1·46, 1·04 to 2·05), increasing age by 10‐year interval (HR 1·30, 1·16 to 1·45), female sex (HR 1·26, 1·01 to 1·59) and thickness of subcutaneous tissue for every 1‐cm increase (HR 1·18, 1·03 to 1·35) were identified as independent risk factors. Compared with superficial I‐SSI, deep I‐SSI was more strongly associated with the development of IH.
Conclusion
Although there are several risk factors for IH, reducing I‐SSI is an important step in the prevention of IH. Registration number: UMIN000004723 (University Hospital Medical Information Network, http://www.umin.ac.jp/ctr/index.htm).
Deep incisional surgical site infection is of major importance
We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. ...PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.
We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR.
CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-β signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients.
PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.
Wnt5a is a representative ligand that activates the β‐catenin‐independent pathways. Because the β‐catenin‐independent pathway includes multiple signalling cascades in addition to the planar cell ...polarity and Ca2+ pathway, Wnt5a regulates a variety of cellular functions, such as proliferation, differentiation, migration, adhesion and polarity. Consistent with the multiple functions of Wnt5a signalling, Wnt5a knockout mice show various phenotypes, including an inability to extend the embryonic anterior–posterior and proximal–distal axes in outgrowth tissues. Thus, many important roles of Wnt5a in developmental processes have been demonstrated. Moreover, recent reports suggest that the postnatal abnormalities in the Wnt5a signalling are involved in various diseases, such as cancer, inflammatory diseases and metabolic disorders. Therefore, Wnt5a and its signalling pathways could be important targets for the diagnosis and therapy for human diseases.
Context.
Dense molecular filaments are ubiquituous in the interstellar medium, yet their internal physical conditions and the role of gravity, turbulence, the magnetic field, radiation, and the ...ambient cloud during their evolution remain debated.
Aims.
We study the kinematics and physical conditions in the Musca filament, the ambient cloud, and the Chamaeleon-Musca complex to constrain the physics of filament formation.
Methods.
We produced CO(2–1) isotopologue maps with the APEX telescope that cut through the Musca filament. We further study a NANTEN2
12
CO(1–0) map of the full Musca cloud, H
I
emission of the Chamaeleon-Musca complex, a
Planck
polarisation map, line radiative transfer models,
Gaia
data, and synthetic observations from filament formation simulations.
Results.
The Musca cloud, with a size of ~3–6 pc, contains multiple velocity components. Radiative transfer modelling of the CO emission indicates that the Musca filament consists of a cold (~10 K), dense (
n
H
2
∼ 10
4
cm
−3
) crest, which is best described with a cylindrical geometry. Connected to the crest, a separate gas component at
T
~ 15 K and
n
H
2
∼ 10
3
cm
−3
is found, the so-called strands. The velocity-coherent filament crest has an organised transverse velocity gradient that is linked to the kinematics of the nearby ambient cloud. This velocity gradient has an angle ≥30° with respect to the local magnetic field orientation derived from
Planck
, and the magnitude of the velocity gradient is similar to the transonic linewidth of the filament crest. Studying the large scale kinematics, we find coherence of the asymmetric kinematics from the 50 pc H
I
cloud down to the Musca filament. We also report a strong C
18
O/
13
CO abundance drop by an order of magnitude from the filament crest to the strands over a distance <0.2 pc in a weak ambient far-ultraviolet (FUV) field.
Conclusions.
The dense Musca filament crest is a long-lived (several crossing times), dynamic structure that can form stars in the near future because of continuous mass accretion replenishing the filament. This mass accretion on the filament appears to be triggered by a H
I
cloud–cloud collision, which bends the magnetic field around dense filaments. This bending of the magnetic field is then responsible for the observed asymmetric accretion scenario of the Musca filament, which is, for instance, seen as a V-shape in the position–velocity (PV) diagram.
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