Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic ...Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
Resistin-like molecule-α (RELMα) has diverse regulatory functions in inflammation, but its role in severe acute pancreatitis (SAP) and acute pancreatitis associated lung injury (APALI) remains ...unclear.
SAP was induced in rats. RELMα protein expression was detected in lung tissue of rats to determine the relationship between APALI and RELMα. To investigate the effect of RELMα overexpression or knockdown on APALI, rats were given an intravenous injection of adenovirus vector before SAP induction. Lung and pancreatic samples were harvested 16 h after induction. After detection of RELMα protein levels, the severity of pancreatic and pulmonary injury was scored histologically, and serum and tissue levels of inflammatory mediators were measured. TUNEL assay and immunofluorescence were used to estimate pulmonary apoptosis and endothelial barrier integrity in lung tissue of SAP rats with RELMα knockdown.
RELMα expression was significantly up-regulated in APALI and was related to the lung injury index. RELMα overexpression aggravated the release of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and serum C-reaction protein; the expression of inflammatory mediators phosphorylated (p)-AKT, p-P65, p-P38 mitogen activated protein kinase, p-extracellular regulated kinase, and intracellular adhesion molecule-1; and lung injury. RELMα knockdown had opposite effects. In addition, RELMα knockdown improved expression of proliferative cellular nuclear antigen, Bcl-2, zonal occluding-1 and Claudin-1 in lung tissue of SAP rats.
RELMα is associated with lung injury severity in SAP. RELMα augments inflammatory activity by increasing inflammatory cytokine release.
The dual role of the microRNA-29 (miR-29) family in tumor progression and metastasis in solid tumors has been reported. Evidence for the role of miR-29 in tumor malignancy and its prognostic value in ...overall survival (OS) and relapse-free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting. Mechanistic studies presented herein demonstrated that c-Myc suppressed the expression of miR-29b, promoting soft agar growth and invasion capability in lung cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc is responsible for soft agar growth and invasiveness mediated by FHIT loss due to promoter methylation. Among patients, low expression of miR-29b and FHIT was more common in tumors with high c-Myc expression than in tumors with low c-Myc expression. Kaplan-Meier and Cox regression analysis showed that tumors with high c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than their counterparts. In conclusion, the decrease in the expression of miR-29b by c-Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b expression using the c-Myc inhibitor might be helpful in suppressing tumor aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC patients with tumors with low expression of FHIT.
The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the ...efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis.
This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis.
A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was -1.3% (95% CI: -7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups.
High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.
Time-resolved 3D-DSA (4D-DSA) enables viewing vasculature from any desired angle and time frame. We investigated whether these advantages may facilitate treatment planning and the feasibility of ...using 4D-DSA as a single imaging technique in AVM/dural arteriovenous fistula radiosurgery.
Twenty consecutive patients (8 dural arteriovenous fistulas and 12 AVMs; 13 men and 7 women; mean age, 45 years; range, 18-64 years) who were scheduled for gamma knife radiosurgery were recruited (November 2014 to October 2015). An optimal volume of reconstructed time-resolved 3D volumes that defines the AVM nidus/dural arteriovenous fistula was sliced into 2D-CT-like images. The original radiosurgery treatment plan was overlaid retrospectively. The registration errors of stereotactic 4D-DSA were compared with those of integrated stereotactic imaging. AVM/dural arteriovenous fistula volumes were contoured, and disjoint and conjoint components were identified. The Wilcoxon signed rank test and the Wilcoxon rank sum test were adopted to evaluate registration errors and contoured volumes of stereotactic 4D-DSA and integration of stereotactic MR imaging and stereotactic 2D-DSA.
Sixteen of 20 patients were successfully registered in Advanced Leksell GammaPlan Program. The registration error of stereotactic 4D-DSA was smaller than that of integrated stereotactic imaging (
= .0009). The contoured AVM volume of 4D-DSA was smaller than that contoured on the integration of MR imaging and 2D-DSA, while major inconsistencies existed in cases of dural arteriovenous fistula (
= .042 and 0.039, respectively, for measurements conducted by 2 authors).
Implementation of stereotactic 4D-DSA data for gamma knife radiosurgery for brain AVM/dural arteriovenous fistula is feasible. The ability of 4D-DSA to demonstrate vascular morphology and hemodynamics in 4 dimensions potentially reduces the target volumes of irradiation in vascular radiosurgery.
Infectious viruses so precisely fit their hosts that the study of natural viral infection depends on host-specific mechanisms that affect viral infection. For human parainfluenza virus 3, a prevalent ...cause of lower respiratory tract disease in infants, circulating human viruses are genetically different from viruses grown in standard laboratory conditions; the surface glycoproteins that mediate host cell entry on circulating viruses are suited to the environment of the human lung and differ from those of viruses grown in cultured cells. Polarized human airway epithelium cultures have been used to represent the large, proximal airways of mature adult airways. Here we modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids derived from human pluripotent stem cells contain mesoderm and pulmonary endoderm and develop into branching airway and alveolar structures. Whole-genome sequencing analysis of parainfluenza viruses replicating in the organoids showed maintenance of nucleotide identity, suggesting that no selective pressure is exerted on the virus in this tissue. Infection with parainfluenza virus led to viral shedding without morphological changes, while respiratory syncytial virus infection induced detachment and shedding of infected cells into the lung organoid lumens, reminiscent of parainfluenza and respiratory syncytial virus in human infant lungs. Measles virus infection, in contrast, induced syncytium formation. These human stem cell-derived lung organoids may serve as an authentic model for respiratory viral pathogenesis in the developing or infant lung, recapitulating respiratory viral infection in the host.
Respiratory viruses are among the first pathogens encountered by young children, and the significant impact of these viral infections on the developing lung is poorly understood. Circulating viruses are suited to the environment of the human lung and are different from those of viruses grown in cultured cells. We modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids, derived from human pluripotent stem cells, develop into branching airway and alveolar structures and provide a tissue environment that maintains the authentic viral genome. The lung organoids can be genetically engineered prior to differentiation, thereby generating tissues bearing or lacking specific features that may be relevant to viral infection, a feature that may have utility for the study of host-pathogen interaction for a range of lung pathogens.
Background
Gastric submucosal tumors are often treated by laparoscopic wedge resection. This study aimed to examine the feasibility of gastric full-thickness resection through a totally endoscopic ...approach using the master and slave transluminal endoscopic robot (MASTER), and closure of the luminal defect with an endoscopic suturing device.
Methods
The operation was performed in two live porcine models under general anesthesia. First, the anterior wall of the stomach was slung to the abdominal wall using a percutaneous suturing device. An imaginary 5-cm lesion was marked using a needle knife. After the initial mucosal incision was made using an IT knife, the MASTER was introduced through a long overtube. A circumferential mucosal incision was completed with the MASTER to expose the muscularis propria which was grasped and incised to the serosal layer by electrocautery applied through the hook of the MASTER. The full-thickness resection of the gastric wall was completed with retraction using the grasper and dissection using the hook. While the defect was being created, the luminal space was maintained with traction of the percutaneous sutures. The defect was closed with suture plication using an Apollo Overstitch device.
Results
Two full-thickness gastric resections were performed in two nonsurvival porcine models (body weight = 30 and 35 kg, respectively) using the MASTER. The total procedure time was 56 min for the first model and 70 min for the second model. The luminal view was maintained during the whole procedure, and there was no damage to surrounding organs throughout the whole procedure. The gastric defects were closed successfully using Overstitch, with satisfactory gastric distension and no gas leakage afterward.
Conclusion
The current experiment demonstrated the feasibility and safety of a totally endoscopic approach for the treatment of gastric submucosal tumors: full-thickness resection with the MASTER and successful closure of the defect using Overstitch.
Development of efficient and durable oxygen evolution reaction (OER) catalysts has a direct impact on the water splitting efficiency and cost effectiveness. In this work, we report the successful ...synthesis of a new Ni(OH)
2
structure, strain-stabilized Ni(OH)
2
nanoribbons (NR-Ni(OH)
2
) two to three layers thick, with widths of 2-5 nm,
via
an electro-oxidation route. Conventional Ni(OH)
2
usually has negligible OER activity, while NR-Ni(OH)
2
shows high activity for the oxygen evolution reaction and an overpotential of 162 millivolts and furthermore exhibits long-term stability in alkaline electrolyte. The substantial reduction in the overpotential of NR-Ni(OH)
2
is due to its easier OOH* adsorption by the active four-coordinated Ni edge sites. The enhanced catalytic activity of NR-Ni(OH)
2
makes it an excellent candidate for industrial applications.
Development of efficient and durable oxygen evolution reaction (OER) catalysts has a direct impact on the water splitting efficiency and cost effectiveness.
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