A new dynamic model of a variable-length rope, which could be used for the transient analysis of a buoy-rope-generator (BRG) wave energy system, was proposed in this paper. The model started from the ...basic dynamic equations of variable mass system, and took into account the physical properties such as axial force, shear and bending. According to the principle of D’Alembert-Lagrange, the equivalent integral weak formulation was firstly obtained, and through consistent linearization and isoparametric discretization, the finite element model of the variable-length rope was then derived. The Bathe scheme was employed to solve the model numerically, based on its excellent performance in solving nonlinear dynamic problems, and an automatic time step size algorithm was designed according to the number of iterations of the two substeps of Bathe scheme. The procedures of rope mesh regeneration were also put forward, where only one variable-length element was always located at the top end of the rope, and the rest were all fixed-length elements. The proposed variable-length rope model and solution schemes were verified through comparison with the results of a tank experiment. Finally, the transient dynamics of a kind of BRG system was analyzed and discussed.
GIST (gastrointestinal stromal tumor) is the most prominent mesenchymal neoplasms of the gastrointestinal tract, and liver is the most common metastasis site for GIST. The molecular mechanism leading ...to liver metastasis of GIST is currently unclear.
With the goal of revealing the underlying mechanism, we performed whole-genome gene expression profiling on 18 pairs of RNA samples comprised of GIST tissues (with liver metastasis) and corresponding non-tumor tissues. After identifying differentially expressed gene, functional annotation and signal pathway analyses were conducted. GSE13861, datasets that compare GIST (without liver metastasis) with adjacent tissues, served as a comparison.
A total of 492 up-regulated genes and 629 down-regulated genes were identified as differentially expressed genes between liver metastasis tissues and non-tumor tissues. We characterized expression patterns of DEGs identified from our cohort and GSE13861 that show signatures of enrichment for functionality. In subsequent gene set enrichment analysis, differentially expressed genes were mainly enriched in Epithelial Mesenchymal Transition in both datasets. 493 genes were overlapped among our whole-genome gene expression profiling results and GSE13861, consisting 188 up-regulated genes and 305 down-regulated genes. By using CytoHubba plugin of Cytoscape, CDH1, CD34, KIT, PROM1, SOX9, FGF2, CD24, ALDH1A1, JAG1 and NES were identified as top ten hub genes in tumorigenesis and liver metastasis of GIST. higher expression levels of FGF2, JAG1, CD34, ALDH1A1 and the lower expression level of CDH1 were respectively associated with unfavorable overall survival. Meanwhile higher expression levels of CD34, FGF2, KIT, JAG1, ALDH1A were correlated with worse disease-free survival.
The present study may help to provide candidate pathways and targets for treatment of GIST and prevention methods to liver metastasis.
Background
Despite the implementation of the 8th American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer (GC) in 2017, it still holds a significant level of stage migration ...which affects patients’ proper classification and accurate prognosis. Here, to reduce this effect, we evaluated the prognostic value of a lymph node ratio (LNR) and established a novel tumor–ratio–metastasis (TRM) staging system.
Method
The data of 15,206 GC patients from the Sun Yat-sen University Cancer Center (Training set; n=2,032) and the US Surveillance, Epidemiology, and End Results (SEER) database (Validation set; n=13,174) were analyzed. The training set was classified into 5 LNR categories, based on which the novel TRM staging system was constructed. The overall survival (OS) between the TRM and AJCC TNM systems was compared in the training set and validated in the validation set. The likelihood ratio
x
2
, liner trend
x
2
, C-index, and Akaike information criterion (AIC) values were used to measure the discriminatory ability between the two different staging systems. Decision curve analyses (DCAs) were conducted to test the clinical value of the two staging systems.
Result
The patients were classified into the following categories: LNR0: 0%, LNR1: 0%<LNR ≤ 10%, LNR2: 10%<LNR ≤ 25%, LNR 3a: 25%<LNR ≤ 60%, and LNR 3b: LNR>60%. Univariate analyses demonstrated that the log-rank
x
2
of the LNR stage (Training/Validation set:
x
2
= 463.1/2880.8) was larger than the AJCC pN stage (Training/Validation set:
x
2
= 281.5/2240.8). For both the training set and validation set, stratified analyses using the Kaplan-Meier method identified significantly heterogeneous OS in every pN category but only one using the LNR. The TRM staging system had higher likelihood ratio
x
2
, liner trend
x
2
, C-index and smaller AIC values than the TNM system.
Conclusion
The TRM staging system demonstrated improved homogeneity and discriminatory ability in predicting the prognosis of GC patients compared with the AJCC TNM staging system.
The atmospheric chemistry of Criegee Intermediates has become a frontier research point in environmental pollution in recent years. In this work, quantum chemical calculations and Born-Oppenheimer ...Molecular Dynamics (BOMD) simulations were employed to explore the gas phase and aqueous interface behavior of the simplest Criegee Intermediate (sCI, CH2OO) and hydrochloric acid (HCl) reaction. Quantum chemical calculations have revealed that the product of ClCH2OOH (CMHP) formation from the CH2OO + HCl reaction without and with water molecule undergoes a barrierless or near barrierless process in the gas phase. The results of the rate coefficients calculated by the master equation indicate that the gas-phase CMHP formation from the reaction of CH2OO + HCl could compete with the hydrolysis of CH2OO with (H2O)2 at the altitude of 15 km. BOMD simulations at the aqueous interfaces show that the CH2OO + HCl reaction occurs through stepwise mechanisms that are distinct from those in the gas phase. Three different interfacial reaction channels were identified: i) CMHP direct formation, ii) water-mediated CMHP formation, and iii) HCl-mediated hydroxymethyl hydroperoxide (HMHP) formation, and completed in picosecond time scales. Considering the harsh reaction conditions between CH2OO and HCl at the interface (i.e., the two molecules must be sufficiently close to form the CH2OO-HCl complex), the route of HMHP formation via the hydrolysis of CH2OO remains the main atmospheric loss pathway of CH2OO at the aqueous interfaces. Interestingly, molecular dynamic simulations in nanosecond time scales reveal that the formed CMHP in the gas phase has a tendency to aggregate with sulfuric acids, ammonia, and water molecules to form stable clusters within 213–278 K. The present results for the CMHP and HMHP formations from the sCI-HCl chemistry in the atmosphere will enhance our comprehension of the atmospheric behavior of Criegee intermediates in urban and marine pollution areas.
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•Clarification of gas phase and aqueous interface reaction mechanisms for CH2OO + HCl.•HCl could be a significant atmospheric scavenger of CH2OO at 15 km altitude.•The aqueous interface CMHP formation mechanism from CH2OO + HCl was confirmed.•Aqueous interface reactions occur in picoseconds and follow a stepwise mechanism.
The hydrolysis of dinitrogen pentoxide (N2O5) is not only a dominant sink for N2O5 under atmospheric conditions but also a critical route in the formation of acid rains and aerosol clusters. Herein, ...the hydrolysis of N2O5 assisted by (H2O)2, H2SO4, H2SO4⋯ H2O, and (H2SO4)2 has been investigated theoretically. The calculations show that, as compared with catalysts of H2O and NH3, the addition of (H2O)2, H2SO4, H2SO4⋯ H2O, and (H2SO4)2 in the hydrolysis of N2O5 not only reduces another energy barrier of 8.7–18.2 kcal mol−1, but also plays a more crucial catalytic role in increasing the reaction rate by at least 2 orders of magnitude within the 213–300 K. Pseudo-first-order rate coefficient (kt′) show that (H2SO4)2-assisted reaction is the favorable hydrolysis of N2O5 assisted by small clusters of sulfuric acid (H2SO4 in 108 molecules ⋅ cm−3 and H2O in 100% RH) with its kt′ respectively larger by 2–6 and 1–5 orders of magnitude. Moreover, (H2O)2–assisted N2O5 + H2O reaction dominates over the reaction without and with (H2SO4)2, H2O (100% RH) and NH3 (2900 ppbv) within the 280–300 K and 0 km altitude, whereas (H2SO4)2–assisted reaction can make an important contribution to the hydrolysis of N2O5 under atmospheric conditions of 213–259 K and 5–15 km. This work helps one understand the process of HNO3 formation from the hydrolysis of N2O5 promoted by water clusters and small clusters of sulfuric acid.
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•The influence of water dimer and small clusters of H2SO4 on the hydrolysis of N2O5 were studied.•Water dimer exerted a better catalytic role than other catalysts in hydrolysis of N2O5 reaction.•(H2SO4)2 will significantly promote the hydrolysis of N2O5 at 213–259 K and 5–15 km.
Suicide is the most severe consequence of depression which has become a leading cause of disability and a global disease burden. Recent evidence indicates a central role of small molecules in the ...pathogenesis of depression and associated suicidal behaviors. However, there lacks a systemic exploration of small molecules in the development of depression-associated suicide, and it remains unclear how they affect an individual's behavior. In order to compare the metabonomic profiles between drug-naïve patients with depression-associated suicidal behaviors and healthy individuals, we conducted a systemic database search for studies of metabolic characteristics in depression-associated suicidal behavior. Manual data curation and statistical analysis and integration were performed in Excel. We further performed an enrichment analysis of signaling pathway prediction using the Reactome Pathway Analysis tool. We have identified 17 metabolites that expressed differently between drug-naïve patients with depression-associated suicidal behaviors and healthy controls. We have integrated these metabolites into biological signaling pathways and provided a visualized signaling network in depressed suicidal patients. We have revealed that "transport of small molecules", "disease", "metabolism" and "metabolism of proteins" were the most relevant signaling sections, among which "transport of inorganic cations/anions and amino acids/oligopeptides", "SLC-mediated transmembrane transport", and "metabolism of amino acids and derivatives" should be further studied to elucidate their potential pathogenic mechanism in the development of depression and associated suicidal behavior. In conclusion, our findings of these 17 metabolites and associated signaling pathways could provide an insight into the molecular pathogenesis of depression-associated suicidal behavior and potential targets for new drug inventions.
Abstract Objective To examine UVB-induced responses in normal human keratinocytes （HaCaT） and epidermoid carcinoma cells （A431） at the cellular and molecular level, and investigated the protective ...effect of salidroside.
Methods Cells irradiated by UVB at various dosage and their viability was assessed by MTT assays, cell cycle was analysed by flow cytometry. The expression of NF-KB, BCL-2, and CDK6 after 50 J/㎡ UVB irradiation were detected by RT-PCR and western blotting.
Results Our results confirmed greater tolerance of A341 cells to UVB-induced damage such as cell viability and cell cycle arrest, which was accompanied by differential expression changes in NF-KB, BCL-2, and CDK6. UVB exposure resulted in HaCaT cells undergoing G1-S phase arrest. When treated with salidroside, HaCaT survival was significantly enhanced following exposure to UVB, suggesting great therapeutic potential for this compound.
Conclusion Taken together, our study suggests that A431 respond differently to UVB than norma HaCaT cells, and supports a role for NF-KB, CDK6, and BCL-2 in UVB-induced cell G1-S phase arrest Furthermore, salidroside can effectively protect HaCaT from UVB irradiation.
On the basis of the Jablonski diagram, the photophysical properties of optical agents are highly associated with biomedical function and efficacy. Herein, the focus is on organic/polymer optical ...agents and the recent progress in the main strategies for regulating their photophysical properties to achieve superior cancer diagnosis/phototheranostics applications are highlighted. Both the approaches of nanoengineering and molecular design, which can lead to optimized effectiveness of required biomedical function, are discussed.
The main strategies for regulating the photophysical properties of organic/polymer optical agents to achieve superior biomedical applications in cancer diagnosis/phototheranosis are highlighted. The approaches of nanoengineering and molecular design, which can lead to optimized effectiveness of required biomedical function, are discussed.
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