Bioinformatics-based analysis reveals elevated CYTL1 as a potential therapeutic target for BRAF-mutated melanoma

Introduction: Despite many recent emerging therapeutic modalities that have prolonged the survival of melanoma patients, the prognosis of melanoma remains discouraging, and further understanding of the mechanisms underlying melanoma progression is needed. Melanoma patients often have multiple genetic mutations, with BRAF mutations being the most common. In this study, public databases were exploited to explore a potential therapeutic target for BRAF-mutated melanoma.Methods: In this study, we analyzed differentially expressed genes (DEGs) in normal tissues and melanomas, Braf wild-type and Braf mutant melanomas using information from TCGA databases and the GEO database. Subsequently, we analyzed the differential expression of CYTL1 in various tumor tissues and its effect on melanoma prognosis, and resolved the mutation status of CYTL1 and its related signalling pathways. By knocking down CYTL1 in melanoma cells, the effects of CYTL1 on melanoma cell proliferation, migration and invasion were further examined by CCK8 assay, Transwell assay and cell migration assay.Results: 24 overlapping genes were identified by analyzing DEGs common to melanoma and normal tissue, BRAF-mutated and BRAF wild-type melanoma. Among them, CYTL1 was highly expressed in melanoma, especially in BRAF-mutated melanoma, and the high expression of CYTL1 was associated with epithelial-mesenchymal transition (EMT), cell cycle, and cellular response to UV. In melanoma patients, especially BRAF-mutated melanoma patients, clinical studies showed a positive correlation between increased CYTL1 expression and shorter overall survival (OS) and disease-free survival (DFS). In vitro experiments further confirmed that the knockdown of CYTL1 significantly inhibited the migration and invasive ability of melanoma cells.Conclusion: CYTL1 is a valuable prognostic biomarker and a potentially effective therapeutic target in melanoma, especially BRAF-mutated melanoma

Molecular mechanism of the treatment of lung adenocarcinoma by Hedyotis Diffusa: an integrative study with real-world clinical data and experimental validation

BackgroundWith a variety of active ingredients, Hedyotis Diffusa (H. diffusa) can treat a variety of tumors. The purpose of our study is based on real-world data and experimental level, to double demonstrate the efficacy and possible molecular mechanism of H. diffusa in the treatment of lung adenocarcinom (LUAD).MethodsPhenotype-genotype and herbal-target associations were extracted from the SymMap database. Disease-gene associations were extracted from the MalaCards database. A molecular network-based correlation analysis was further conducted on the collection of genes associated with TCM and the collection of genes associated with diseases and symptoms. Then, the network separation SAB metrics were applied to evaluate the network proximity relationship between TCM and symptoms. Finally, cell apoptosis experiment, Western blot, and Real-time PCR were used for biological experimental level validation analysis.ResultsIncluded in the study were 85,437 electronic medical records (318 patients with LUAD). The proportion of prescriptions containing H. diffusa in the LUAD group was much higher than that in the non-LUAD group (p < 0.005). We counted the symptom relief of patients in the group and the group without the use of H. diffusa: except for symptoms such as fatigue, palpitations, and dizziness, the improvement rate of symptoms in the user group was higher than that in the non-use group. We selected the five most frequently occurring symptoms in the use group, namely, cough, expectoration, fatigue, chest tightness and wheezing. We combined the above five symptom genes into one group. The overlapping genes obtained were CTNNB1, STAT3, CASP8, and APC. The selection of CTNNB1 target for biological experiments showed that the proliferation rate of LUAD A549 cells in the drug intervention group was significantly lower than that in the control group, and it was concentration-dependent. H. diffusa can promote the apoptosis of A549 cells, and the apoptosis rate of the high-concentration drug group is significantly higher than that of the low-concentration drug group. The transcription and expression level of CTNNB1 gene in the drug intervention group were significantly decreased.ConclusionH. diffusa inhibits the proliferation and promotes apoptosis of LUAD A549 cells, which may be related to the fact that H. diffusa can regulate the expression of CTNNB1

결속원리의 비교분석-중국어, 한국어, 영어를 중심으로

In the late 1980s, Chomsky proposed the “Government and Binding theory” based on the original theory of transformational generative grammar. Binding theory, as a subtheory of GB, is a theoretical generalization of the referential dissimilarity between noun phrases in the same utterance and the related conditional restrictions. The properties and morphology of reflexive pronouns in various languages have been a hot topic of debate in linguistics since Chomsky proposed the Binding theory. The first principle of Binding theory points out that the anaphor is bound within its binding domain, and reflexive pronouns belong to the category of anaphor language, so Binding theory can be closely related to the study of the properties of reflexive pronouns, i.e. morphology. The second principle pronouns are free within their binding domain, and the third principle Rexpression (referential expression) must be free in any domain. Based on this theory, Chomsky and his successors have done a lot of research on reflexive pronouns in different languages. Among them, the study of Korean and Chinese reflexive pronouns has also received a lot of attention from linguists. In view of the previous analysis, this paper takes the Chinese pronouns ziji, ta-ziji, Korean pronouns caki, casin, kunyecasin kucasin and English himself, herself as the objects of study. The concepts of C-command, governing category, Local domain, Longdistance binding and phi-feature specification and anaphoric dependency of reflexive pronouns are used for comparative analysis under the framework of Binding theory. Overall, this study provides new insights into the syntax of Chinese, Korean, and English reflexive pronouns, and is important for understanding the development of reflexive pronouns from a linguistic perspective. It also provides pedagogical insights for English scholar-users. Key words Reflexive pronouns, binding theory, referentiality, anaphorContents List of Abbreviations ···················································································· ii Figure Contents ························································································· iii Chapter 1 Introduction ·················································································· 1 1.1 Research background ······································································ 1 1.2 Purpose of Research ········································································2 1.3 Significance of Research ·································································· 2 1.4 Thesis organization·········································································· 3 Chapter 2 Literature Review ············································································4 2.1 Theoretical Framework ···································································· 4 2.1.1 The Binding Theory···································································4 2.1.2 Domain issues and local vs. long-distance binding (LDB)····················· 14 2.1.3 Abstract Movement··································································19 2.2 Previous studies on the reflexive binding in three languages ························21 Chapter 3 Local vs. Long Distance Binding based on Referential Hierarchy···················· 28 3.1 Variation in Binding Distance based on Referential Hierarchy·······················28 3.1.1 Binding Distance –Relative Phenomenon········································ 29 3.1.2 Defining Referentiality based on Lexical Contents······························30 3.1.3 How Local vs. Long Distance Dependency Works······························34 3.1.4 Direction in Binding Phenomena·················································· 41 3.2 Relativity in Principle B Effects·························································· 53 3.3 Reciprocals Anaphors······································································60 3.4 Bimorphemic Anaphors··································································· 65 3.4.1 Do Chinese and Korean have genuine local anaphors?························· 66 3.4.2 Restructuring········································································· 71 3.4.3 Referential Hierarchy revisited·····················································77 5. References ···························································································· 83Maste

A bifunctional additive bi(4-flurorophenyl) sulfone for enhancing the stability and safety of nickel-rich cathode based cells

LiNi0.8Co0.1Mn0.1O2 is regarded as a promising cathode material in lithium ion batteries (LIB) for its high specific capacity and low cost. While the short cycle life, severe cathode deterioration as well as the poor safety characteristic hinder its wide application. In this work, we introduce a novel additive, bis(4-fluorophenyl) sulfone (BFS), which enhances the capacity retention from 75.19% to 83.04% after 100 cycles at the rate of 1C. Moreover, linear sweep voltammetry (LSV), cyclic voltammetry (CV), galvanostatic test, scanning electron microscope (SEM), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy were carried out to further demonstrate the superiority of this additive. We prove that this additive can decompose preferentially and form a desirable cathode electrolyte interface on the positive cathode according to the LSV and TEM results. Furthermore, the smooth and robust film not only can effectively enhance the cycling stability, but also can prevent the cathode from severe deterioration. We deduce a proper function mechanism of this additive. This additive can be oxidized at state of charge into two sulfonates, which prevent the carbonate electrolyte from decomposition. This mechanism has been proved by DFT calculations. In addition, the overcharging performance also has been tested in this work by charging cells till 5 V. (C) 2019 Elsevier B.V. All rights reserved.</p

3-cyano-5-fluorobenzenzboronic acid as an electrolyte additive for enhancing the cycling stability of Li1.2Mn0.54Ni0.13Co0.13O2 cathode at high voltage

Layered lithium/manganese-rich oxides (LMR) receive much attention due to its high specific capacity (similar to 300 mAh g(-1)). However, the serious capacity degradation during cycling hinders the commercial application of the LMR. Herein, 3-cyano-5-fluorophenylboronic acid (CFBA) was applied as an electrolyte additive for enhancing the cycling stability of LMR at high voltage. Linear sweep voltammetry (LSV), density function theory (DFT) calculations and the initial charge dQ/dV profiles indicate that the preferential oxidation of CFBA can improve the oxidative stability of electrolyte. By adding 0.7 wt% CFBA into standard (STD) electrolyte (1 M LiPF6 in EC:EMC:DMC = 1:1:1, by weight), the LMR/Li half-cell delivered a discharge capacity of 245 mAh g(-1) with a capacity retention of 88.4% after 200 cycles at 0.5C, while only 68 mAh g(-1) with 25.2% retention in STD electrolyte. Further characterizations and theoretical calculation illustrate that CFBA can effectively eliminate the harmful HF, which improve the electrochemical performance. More importantly, the CFBA participates in the formation of a thin and uniform protective cathode-electrolyte interface (CEI) film on the surface of LMR, which effectively suppresses electrolyte decomposition and protects the structural integrity of LMR. (C) 2020 Elsevier B.V. All rights reserved

Robust Electrocatalytic Li2S Redox of Li-S Batteries Facilitated by Rationally Fabricated Dual-Defects

The commercialization of lithium-sulfur batteries with ultra-high theoretical energy density is restricted mainly by the notorious polysulfides "shuttle effect" and slow Li2S redox reaction kinetics. A sulfur host material with high catalytic activity and high conductivity is greatly desired to improve its electrochemical performance. Herein, a sulfur host material, etched cotton@petroleum asphalt carbon (eCPAC), with high specific surface area and excellent catalytic activity, is demonstrated based on a synergistic strategy of introducing intrinsic lattice defects and composite carbon structure. Benefiting from in situ coupling of amorphous and crystalline materials, eCPAC exhibits high conductivity and high sulfur adsorbability. Furthermore, eCPAC containing dual intrinsic defect sites can catalyze the bidirectional sulfur chemistry of Li2S and capture polysulfides, which is also demonstrated by systematic density functional theory calculations and the potential intermittent titration technique. S@eCPAC/Li cells exhibit excellent cycling stability and rate performance, with an average capacity decay rate of only 0.05% over 1000 cycles at 0.5 C and even 0.03% over 600 cycles at 5 C. Meanwhile, the practicality of eCPAC is proven in high-load batteries and pouch batteries. eCPAC provides a reliable strategy for achieving a win-win situation of capturing polysulfides and accelerating Li2S redox kinetics

Robust Electrocatalytic Li2S Redox of Li-S Batteries Facilitated by Rationally Fabricated Dual-Defects

The commercialization of lithium-sulfur batteries with ultra-high theoretical energy density is restricted mainly by the notorious polysulfides "shuttle effect" and slow Li2S redox reaction kinetics. A sulfur host material with high catalytic activity and high conductivity is greatly desired to improve its electrochemical performance. Herein, a sulfur host material, etched cotton@petroleum asphalt carbon (eCPAC), with high specific surface area and excellent catalytic activity, is demonstrated based on a synergistic strategy of introducing intrinsic lattice defects and composite carbon structure. Benefiting from in situ coupling of amorphous and crystalline materials, eCPAC exhibits high conductivity and high sulfur adsorbability. Furthermore, eCPAC containing dual intrinsic defect sites can catalyze the bidirectional sulfur chemistry of Li2S and capture polysulfides, which is also demonstrated by systematic density functional theory calculations and the potential intermittent titration technique. S@eCPAC/Li cells exhibit excellent cycling stability and rate performance, with an average capacity decay rate of only 0.05% over 1000 cycles at 0.5 C and even 0.03% over 600 cycles at 5 C. Meanwhile, the practicality of eCPAC is proven in high-load batteries and pouch batteries. eCPAC provides a reliable strategy for achieving a win-win situation of capturing polysulfides and accelerating Li2S redox kinetics

Constructing interfacial gradient layers and enhancing lithium salt dissolution kinetics for high-rate solid-state batteries

The stability of the interfacial layers depends mainly on the composition and distribution of the decomposition products from solid-state electrolytes (SSEs) in lithium metal batteries. Therefore, the design of SSEs becomes an attractive way to construct a homogeneous stable interfacial layer. Herein, pentafluorostyrene (PFS) as a block is used to generate robust interfacial layers for solid-state batteries. Meanwhile, PFS facilitates the dissociation of lithium salts to produce more free Li-ions which can enhance the ionic conductivity from the results of 7Li solid-state NMR spectra, density functional theory, and molecular dynamics calculations. Subsequently, XPS depth etching and TOF-SIMS characterizations together show that the gradient interfacial layer is composed of a rich C-F bond surface layer and a rich-LiF & Li3N bottom layer, enabling rapid transport and uniform deposition of lithium ions. As a result, the Li/Li symmetric cell can achieve a stable ultra-long cycle time of more than 3000 h at 0.2 mA cm(-2) and a critical current density of 2.4 mA cm(-2). The as-prepared SSE exhibits a high ionic conductivity of 4.3 x 10(-4) S cm(- 1) at 25 C and remarkable cycling stability at 0 C and -20 ?. Moreover, the lithium metal batteries based on as-prepared SSEs deliver high-rate (2 C) capability and high-voltage (NCM811) stability at room temperatures

Ultra-stable high voltage lithium metal batteries enabled by solid garnet electrolyte surface-engineered with a grafted aromatics layer

The instability and Li2CO3 contaminants of garnet-type electrolytes exposed to air could lead to in its poor interfacial contact with the lithium metal. Generally, the thermal treatment temperature of garnet should overpass 700 & DEG;C to remove surface contaminants. Herein, we report a low temperature method in which con-taminants are converted to the aromatics lithiophilic interface via a simple azo reaction at 60 & DEG;C. The free radicals formed by the decomposition of the azo compound are grafted onto garnet, thereby the garnet compatibility in lithium metal batteries (LMBs) are improved effectively. The reaction mechanism is confirmed by density functional theory calculations, comprehensive electrochemical characterizations, and applying designed azo compounds. The modified garnet membrane shows a high mechanical property and reduced interfacial impedance, high Young's modulus of 169.99 GPa and ionic conductivity of 0.457 mS/cm at 20?. Subsequently, combined XPS depth etching and TOF-SIMS characterizations show that the interfacial layer is composed of a rich C-F bond surface layer and a rich-LiF bottom layer, enabling rapid transport and uniform deposition of lithium ions. Moreover, the superior cycling stability facilitated by modified composite electrolyte is demonstrated in Li/LiFePO4 and Li/LiNi0.5Co0.2Mn0.3O2 full batteries. This new conversion chemistry via azo compound provides a practical solution for achieving high-energy solid-state LMBs

Proteomic analysis of the low mutation rate of diploid male gametes induced by colchicine in Ginkgo biloba L.

Colchicine treatment of G. biloba microsporocytes results in a low mutation rate in the diploid (2n) male gamete. The mutation rate is significantly lower as compared to other tree species and impedes the breeding of new economic varieties. Proteomic analysis was done to identify the proteins that influence the process of 2n gamete formation in G. biloba. The microsporangia of G. biloba were treated with colchicine solution for 48 h and the proteins were analyzed using 2-D gel electrophoresis and compared to protein profiles of untreated microsporangia. A total of 66 proteins showed difference in expression levels. Twenty-seven of these proteins were identified by mass spectrometry. Among the 27 proteins, 14 were found to be up-regulated and the rest 13 were down-regulated. The identified proteins belonged to five different functional classes: ATP generation, transport and carbohydrate metabolism; protein metabolism; ROS scavenging and detoxifying enzymes; cell wall remodeling and metabolism; transcription, cell cycle and signal transduction. The identification of these differentially expressed proteins and their function could help in analysing the mechanism of lower mutation rate of diploid male gamete when the microsporangium of G. biloba was induced by colchicine