The RON receptor tyrosine kinase is a member of the MET proto-oncogene family that has been implicated in regulating motile-invasive phenotypes in certain types of epithelial cancers. The purpose of ...this study was to determine if RON expression is altered in primary human colorectal adenocarcinomas. Results from immunohistochemical staining showed that RON is highly expressed in the majority of colorectal adenocarcinomas (29/49 cases). Accumulated RON is also constitutively active with autophosphorylation in tyrosine residues. Moreover, three splicing variants of RON, namely RONdelta165, RONdelta160, and RONdelta155 were detected and cloned from two primary colon cancer samples. These RON variants were generated by deletions in different regions in extracellular domains of the RON beta chain. Functional studies showed that expression of RONdelta160 or RONdelta155 in Martin-Darby canine kidney cells resulted in increased cell dissociation (scatter-like activity). RON variants, RONdelta160 and RONdelta155, also exerted the ability to induce multiple focus formation and sustain anchorage-independent growth of transfected NIH3T3 cells. Moreover, NIH3T3 cells expressing RONdelta160 or RONdelta155 formed tumors in athymic nude mice and colonized in the lungs. These data suggest that RON expression is altered in certain primary colon cancers. Abnormal accumulation of RON variants may play a role in the progression of certain colorectal cancers in vivo.
The relationship between baseline cognitive impairment (CI) and incident visual impairment (VI) in Asians is unclear.
To determine the associations between baseline CI with incident VI and visual ...acuity (VA) at 6-year follow-up in multiethnic Asians.
Cohort.
Population-based.
Two thousand three hundred and twenty-four adults aged ≥60 years from the Singapore Epidemiology of Eye Diseases Study (response rate 64%).
CI was defined using the validated Abbreviated Mental Test (AMT). VA was objectively measured using a LogMAR chart. Any incident VI was defined as having no VI (Snellen's VA better than or equal to 20/40) at baseline but present (VA worse than 20/40) at 6-year follow-up. VI severity was defined according to the International Classification of Diseases, 11th Revision. Associations were assessed using logistic and linear regression models.
Of the 2,324 participants, 248 had CI at baseline. Presence of baseline CI was associated with more than twice the odds of any incident VI, incident mild and moderate-severe VI (OR 95% confidence interval: 2.48 1.55-3.90, 2.07 1.17-3.55, and 2.61 1.36-4.93, respectively) and worse VA (β 95% confidence interval: 0.026 0.006-0.046) at 6-year follow-up. The leading causes of incident VI were cataract and under-corrected refractive error.
Older adults with CI had more than double the odds of VI development and poorer VA than their cognitively intact counterparts, and most causes of incident VI were correctable. Strategies such as targeted vision screening and early intervention for early detection and management of vision loss in patients with cognitive decline are warranted.
Transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy were used to study the microstructure evolution of Al-Cu-Mg alloy during the initial stage of homogenization. It was ...found that two types of precipitation-free zones (PFZs) can form concurrently: one near grain boundaries and the other at the grain centres. Depth profile analyses of solute concentrations and dislocation-loop distributions strongly suggested that the formations of the two type of PFZs are different, due solely and exclusively to solute and vacancy depletion, respectively. A mechanism model was proposed to explain the concurrent formation of the two different type of PFZs during the initial stage of homogenization.
Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel ...therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase that regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD) that plays a vital role in energy metabolism. Here, we show that KPT-9274 strongly inhibits B-ALL cell growth regardless of cytogenetic abnormalities. We also demonstrate the potent in vivo efficacy and tolerability of KPT-9274 in a patient-derived xenograft murine model of B-ALL. Interestingly, although KPT-9274 is a dual PAK4/NAMPT inhibitor, B-ALL cell growth inhibition by KPT-9274 was largely abolished with nicotinic acid supplementation, indicating that the inhibitory effects on B-ALL cells are mainly exerted by NAD
depletion through NAMPT inhibition. Moreover, we have found that the extreme susceptibility of B-ALL cells to NAMPT inhibition is related to the reduced cellular NAD
reserve. NAD
depletion may be a promising alternative approach to treating patients with B-ALL.
To investigate the regulation of long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) on proliferation, invasion, and aerobic glycolysis in glioma cells via miR-140-5p.
Sixty ...patients with glioma treated in our hospital were recruited. The expression of PVT1 in tissues and cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the effects on the prognosis were observed. Glioma cell lines U87 and T98MG were either stably or transiently transfected with over-expression or inhibition vectors. Cell counting kit-8 (CCK-8), transwell, glucose, and lactate detection were employed to measure cell proliferation, invasion, and aerobic glycolysis after transfection. The correlation between PVT1 and miR-140-5p was determined by Dual-Luciferase reporter assay. RNA pull-down and RNA immunoprecipitation (RIP) test were adopted to indicate the correlation between PVT1 and miR-140-5p.
PVT1 was highly expressed and had superior diagnostic value in gliomas, and the high expression of PVT1 resulted in poor prognosis of patients. Over-expressing PVT1 increased cell proliferation, invasion, and aerobic glycolysis, while inhibiting PVT1 yielded opposite outcome. Dual-Luciferase reporter assay confirmed that PVT1 could target miR-140-5p. Functional analysis showed that over-expression of miR-140-5p inhibited proliferation, invasion, and aerobic glycolysis in glioma cells. Rescue experiment found that the inhibitory effect of miR-140-5p could be eliminated by up-regulating PVT1 expression.
PVT1 promotes proliferation, invasion, and aerobic glycolysis in glioma cells by regulating miR-140-5p.
The ESD effects on the E-mode AlGaN/GaN high-electron mobility transistors (HEMTs) with p-GaN gate are investigated under repetitive TLP pulses. Firstly, the degradation and recovery of output, ...transfer characteristics, gate-leakage characteristics and low-frequency noises (LFN) are analyzed in detail before and after reverse electrostatic discharge (ESD) stress. The experimental results show that the electrical characteristics of the devices gradually degraded as the transmission line pulse (TLP) pules increased. Subsequently, the LFN measurements are performed over the frequency range of 1 Hz-10 KHz by increasing TLP pulses. Finally, the recovery tendency of DC (direct current) characteristics and trap density are studied and discussed after resting the device at room temperature for 1 to 3 months. These results physically confirm that the mechanism of the performance degradation and recovery of the devices could be attributed to the trapping and releasing processes of electrons in the p-GaN layer and AlGaN barrier layer of AlGaN/GaN HEMTs, which change the electric field distribution under the gate.
Reperfusion is considered as the cornerstone of the treatment of high-risk pulmonary embolism (PE). However, when thrombolysis is contraindicated and surgery or interventional therapy is not ...available, the treatment of high-risk PE becomes very difficult. To our knowledge, there are no reports of successful treatment of high-risk PE with low-dose anticoagulation. On November 30, 2021, a 56-year-old male patient with subarachnoid hemorrhage was admitted to the emergency department of the First Affiliated Hospital of Chongqing Medical University. On the second day of admission, the patient suddenly went into shock during aneurysm clipping. After implementing D-dimer, markers of myocardial injury, echocardiography and computed tomography pulmonary angiography, a high-risk PE was diagnosed. Due to the contraindication of thrombolysis and the refusal of endovascular treatment, he was eventually cured with low-dose anticoagulation combined with vasopressors.
A large high-altitude air shower observatory is to be built at Yang-Ba-Jing, Tibet, China. One of its main purposes is to survey the northern sky for very-high-energy (above 100GeV) gamma ray sources ...via its ground-based water Cherenkov detector array. To gain full knowledge of water Cherenkov technique in detecting air showers, a prototype water Cherenkov detector is built at the Institute of High Energy Physics, Beijing. The performance of the prototype water Cherenkov detector is studied by measuring its response to cosmic muons. The results are compared with those from a full Monte Carlo simulation to provide a series of information regarding the prototype detector in guiding electronics design and detector optimization.
Aim
The objective of this study was to investigate the biofilm inhibitory activity of Streptomyces‐derived actinomycin D against biofilm formation by Staphylococcus epidermidis.
Methods and Results
...The microtitre plate method and microscopy were used to detect the biofilm formation of S. epidermidis. And an attempt was made to detect the effect of actinomycin D on important biofilm components, exopolysaccharides (EPS) in S. epidermidis using precolumn derivation HPLC. Also cell surface hydrophobicities of S. epidermidis were assessed to explore action mechanisms. The qPCR was performed to demonstrate the genetic mechanisms of biofilm formation by S. epidermidis. Unlike other antibiotics, actinomycin D (1·5 μg ml−1) from Streptomyces luteus significantly inhibited biofilm formation by S. epidermidis. Additionally, it effectively inhibited S. epidermidis cells from adhering to glass slides. Actinomycin D downregulated ica locus and then the reduced polysaccharide intercellular adhesin production caused S. epidermidis cells to become less hydrophobic, thus supporting its anti‐biofilm effect.
Conclusion
Streptomyces‐derived actinomycin D is active in inhibiting the biofilm formation of S. epidermidis.
Significance and Impact of the Study
Actinomycin D can be used as a promising antibiofilm agent in inhibiting S. epidermidis biofilm formation. The study is also the first insight into how actinomycin D inhibited the biofilm formation of S. epidermidis. Actinomycin D could potentially be used to reduce the risk of biofilm‐associated infections. Our study also suggests that the metabolites from Actinomycete strains keep further attention as potential antibiofilm agents against biofilm formation of S. epidermidis, even biofilm infections of the other bacteria.
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