Enhancing Na^(+) diffusion dynamics and structural stability of O3-NaMn_(0.5)Ni_(0.5)O_(2)cathode by Sc and Zn dual-substitution

Sc and Zn were introduced into O3-NaMn_(0.5)Ni_(0.5)O_(2)(NaMN)using the combination of solution combustion and solid-state method.The effect of Sc and Zn dual-substitution on Na^(+) diffusion dynamics and structural stability of NaMN was investigated.The physicochemical characterizations suggest that the introduction of Sc and Zn broaden Na^(+) diffusion channels and weaken the Na—O bonds,thereby facilitating the diffusion of sodium ions.Simulations indicate that the Sc and Zn dual-substitution decreases the diffusion barrier of Na-ions and improves the conductivity of the material.The dual-substituted NaMn_(0.5)Ni_(0.4)Sc_(0.04)Zn_(0.04)O_(2)(Na MNSZ44)cathode delivers impressive cycle stability with capacity retention of 71.2%after 200 cycles at 1C and 54.8%after 400 cycles at 5C.Additionally,the full cell paired with hard carbon anode exhibits a remarkable long-term cycling stability,showing capacity retention of 64.1%after 250 cycles at 1C.These results demonstrate that Sc and Zn dual-substitution is an effective strategy to improve the Na^(+) diffusion dynamics and structural stability of NaMN.

A systematic study of Erzhu Erchen decoction against damp-heat internalized type 2 diabetes based on data mining and experimental verification

Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.

2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-Glucoside modulates CHEK2 and CCND1 alternative splicing to inhibit MCF-7 cells proliferation

Background:In our previous study,we observed a synergistic effect of 2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-glucoside combined with adriamycin to induce apoptosis in MCF-7 breast cancer cells.However,the underlying mechanisms of epigenetic modifications,such as alternative splicing,have not been explored.In this study,we aimed to investigate the mechanism by which THSG inhibits MCF-7 cell proliferation using full-length transcriptome sequencing.Methods:First,cell viability was examined using the methyl thiazolyl tetrazolium method and full-length transcriptome sequencing was performed to identify genes and pathways.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify the principal pathways and targets of THSG.Flow cytometry analysis of cell cycle distribution was performed.Meanwhile,the analysis of alternative splicing and domains of the key proteins was conducted.Quantitative polymerase chain reaction and western blotting were performed for verification.Results:THSG showed significant cytotoxic activity in MCF-7 cells.Full-length transcriptome sequencing revealed differential alternative splicing with 173 upregulated and 263 downregulated genes.Further analysis identified distinct differential expression of genes(CHEK2-211 and CCND1-201)involved in the cell cycle in the THSG-treated group.Subsequently,alternative splicing types of CHEK2(mutually exclusive exon)and CCND1(intron retention).We found that THSG downregulated mRNA expression,as confirmed by quantitative polymerase chain reaction analysis.Interestingly,protein structural analysis revealed that THSG treatment led to the generation of CHK2-211,which was the result of a mutation in the amino acid residues(GLU-150,ASN-151)of the CHEK2 domain(VAL-150,GLY-151).and CyclinD1-201 were obtained when an amino acid(ASP-267)in the domain was lost in CyclinD1.Moreover,molecular docking analysis demonstrated that the domains of key proteins could bind THSG more effectively,with no difference in affinity.Western blotting confirmed that THSG inhibited the expression of CHK2 and CyclinD1.Conclusion:THSG modulated the alternative splicing of CHEK2 and CCND1 by inducing G0/G1 cell cycle arrest,consequently suppressing MCF-7 cell proliferation.

A bioinformatics-based study of the mechanism of JQ-1 on BET protein and atherosclerosis induced by vascular smooth muscle cell proliferation

Background:Based on previous theoretical studies,JQ-1 as a common inhibitor of bromodomain and extraterminal(BET)proteins was used to treat a variety of diseases.Therefore,we aimed to explore the mechanism of action of JQ-1 on BET proteins based on bioinformatics and build the novel hypothesis of JQ-1 in treating atherosclerosis(AS)caused by proliferation of vascular smooth muscle cells(VSMCs).Methods:We selected the chip GSE138323 which was searched with the key words“Vascular smooth muscle cell proliferation”in Gene Expression Omnibus(GEO)database,and differential gene analysis was performed between the GRO and JQ-1 groups.Then the top twenty significantly up-regulated genes and the top twenty significantly down-regulated genes were selected for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Thirdly,structured the PPI network of forty differential genes,and the core genes were screened by using the MCC algorithm which in“Cytohubba”plugin in the Cytoscapev3.9.1 software.After that,single gene Gene Set Enrichment Analysis(GSEA)enrichment analysis was performed on the selected core genes in R language.Finally molecular docking validation was performed.Results:Five core genes was selected:H3C2,H3C4,H3C7,H3C10 and AREG.The GO enrichment analysis results showed that there were twenty-five entries in biological process,eight entries in cellular components(CC),and twenty-five entries in molecular function.The KEGG enrichment analysis results showed that there were seven pathways,mainly including systemic lupus erythematosus and external neutrophil trap formation.The GSEA results showed that the five genes were mainly through the regulation of cytochrome P450 metabolism,PPAR signaling pathway and other pathways.The molecular docking results showed that JQ-1 had binding activity with these five genes.Conclusions:JQ-1 may regulate the expression of the genes that H3C2,H3C4,H3C7,H3C10 and AREG,to mainly regulate the genes in cytochrome P450 metabolism,PPAR singling pathway and other pathways,to make some influence in the proliferation of VSMCs,and improved atherosclerotic symptoms due to vascular smooth muscle proliferation,thus treating cardiovascular disease.

To explore the mechanism of Naodesheng tablets in the treatment of atherosclerosis based on network pharmacology and bioinformatics

Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinformatics,predict the relevant targets and signalling pathways for NDST in the treatment of atherosclerosis.Methods:First,the targets of NDST and the targets for treating atherosclerosis were looked for in different databases.Next,Venny 2.1.0 was used to find the genes that overlapped between NDST and targets for treating atherosclerosis.Subsequently,the herb-active ingredient-target-disease were obtained to explore the hub compound.Furthermore,the Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“active ingredient-intersection target-pathway”network by Cytoscape software to gain the hub genes and pathways.Finally,molecular docking was used to verify the affinity of hub ingredients and hub genes.Results:In the results,67 active ingredients and 322 targets of NDST were selected in ingredients-targets network.154 overlapping targets of NDST(322)and atherosclerosis(1330)were obtained.Then,the herb-active ingredient-target-disease showed that quercetin,apigenin and luteolin were the hub ingredients to treat atherosclerosis.Further,the hub genes(PTGS2,RXRA,CASP3)and pathways(lipid and atherosclerosis)were accessed in active ingredient-intersection target-pathway.Finally,the results indicated that quercetin,apigenin and luteolin were better binding the PTGS2,RXRA,CASP3,especially PTGS2 and luteolin in molecular docking.Conclusion:In conclusion,quercetin,apigenin and luteolin,as the main ingredients of NDST could play a important role in PTGS2,RXRA,and CASP3 for treating atherosclerosis via the lipid and atherosclerosis(TNF signaling pathway).

Network pharmacology and molecular docking techniques to explore the mechanism of Smilax china L.in the treatment of myocardial infarction

Objective:To predict the relevant targets and signaling pathways of Smilax china L.(SC)for treating myocardial infarction on the basis of network pharmacology and molecular docking.Consequently,the basis for additional in-depth investigation is obtained.Methods:First,the targets of SC and the targets for treating myocardial infarction were screened from different databases,Then the intersection genes of SC for treating myocardial infarction were performed in Venny 2.1.0.Second,to obtain the protein interaction network,the Metascape database,String database,were used to analyze the important modules related to the signaling pathway using MCODE algorithm.Furthermore,the DAVID database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“interaction targets-pathways”network by Cytoscape software,and using Network Analyzer was used to screen the core compound,core targets and core pathways.Finally,molecular docking was used to verify whether the core compounds and core targets had better docking binding.Results:11 active ingredients and 98 targets of SC,1846 targets to treat myocardial infarction and 58 targets related to treat myocardial infarction in SC were obtained;MCODE analysis of the protein-protein interaction network yielded 4 important modules related to signaling pathways;Gene Ontology enrichment analysis yielded 848 entries and Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 144 signaling pathways;the core compounds were beta-sitosterol,diosgenin,kaempferol,core targets were AKT1,CASP9,BCL2,core pathways were pathways in cancer,pathways of neurodegeneration-multiple diseases,Kaposi’s sarcoma-associated herpesvirus infection,lipid and atherosclerosis and human cytomegalovirus infection.Finally,molecular docking between core components and core targets was verified.Conclusion:The preliminary prediction of the mechanism of the SC in the treatment of myocardial infarction is that it acts through a multi-compounds,multi-targets and multi-pathways.This study provided a theoretical basis and research direction for the mechanism of action of SC in the treatment of myocardial infarction,and lays the foundation for further research on SC in the treatment of myocardial infarction.

Energy loss of degrader in SC200 proton therapy facility

The proton beam energy determines the range of particles and thus where the dose is deposited. According to the depth of tumors, an energy degrader is needed to modulate the proton beam energy in proton therapy facilities based on cyclotrons, because the energy of beam extracted from the cyclotron is fixed. The energy loss was simulated for the graphite degrader used in the beamline at the superconducting cyclotron of 200 MeV in Hefei(SC200). After adjusting the mean excitation energy of the graphite used in the degrader to 76 eV, we observed an accurate match between the simulations and measurements.We also simulated the energy spread of the degraded beam and the transmission of the degrader using theoretical formulae. The results agree well with the Monte Carlo simulation.

Control strategy optimization using dynamic programming method for synergic electric system on hybrid electric vehicle

Dynamic Programming (DP) algorithm is used to find the optimal trajectories under Beijing cycle for the power management of synergic electric system (SES) which is composed of battery and super capacitor. Feasible rules are derived from analyzing the optimal trajectories, and it has the highest contribution to Hybrid Electric Vehicle (HEV). The methods of how to get the best performance is also educed. Using the new Rule-based power management strat-egy adopted from the optimal results, it is easy to demonstrate the effectiveness of the new strategy in further improvement of the fuel economy by the synergic hybrid system.

Effectiveness of urban distributed runoff model for discharge and water depth calculation in urban drainage pipe networks

Effective urban land-use re-planning and the strategic arrangement of drainage pipe networks can significantly enhance urban flood defense capacity.Aimed at reducing the potential risks of urban flooding,this paper presents a straightforward and efficient approach to an urban distributed runoff model(UDRM).The model is developed to quantify the discharge and water depth within urban drainage pipe networks under varying rainfall intensities and land-use scenarios.The Nash efficiency coefficient of UDRM exceeds 0.9,which indicates its high computational efficiency and potential benefit in predicting urban flooding.The prediction of drainage conditions under both current and re-planned land-use types is achieved by adopting different flood recurrence intervals.The findings reveal that the re-planned land-use strategies could effectively diminish flood risk upstream of the drainage pipe network across 20-year and 50-year flood recurrence intervals.However,in the case of extreme rainfall events(a 100-year flood recurrence),the re-planned land-use approach fell short of fulfilling the requirements necessary for flood disaster mitigation.In these instances,the adoption of larger-diameter drainage pipes becomes an essential requisite to satisfy drainage needs.Accordingly,the proposed UDRM effectively combines land-use information with pipeline data to give practical suggestions for pipeline modification and land-use optimization to combat urban floods.Therefore,this methodology warrants further promotion in the field of urban re-planning.

ARHGAP4 variants are associated with X-linked early-onset temporal lobe epilepsy

The ARHGAP4 gene(OMIM*300,023),also known as Rho GTPase activating protein 4,encodes a protein that has an essential role in the regulation of small GTP-binding.ARHGAP4 message RNA(mRNA)is highly expressed during the developing and adult nervous system.At the protein level,ARHGAP4 is exclusively present in certain brain regions,such as the mesial temporal lobe,specifically the stratum lucidum of the CA3 region[1].ARHGAP4 enhances the GTPase activity of Rho proteins,which modulate morphological alterations in neuron development and synaptic plasticity by interacting with the actin cytoskeleton[2].

Recent advances in tribological and wear properties of biomedical metallic materials

Biomedical metallic materials are commonly used in the repair and replacement of human tissues.After the materials are implanted in the human body,the implants can rub against human tissue or other implants,resulting in wear and tear of the implants.The wear and tear of implants in the human body can lead to osteolysis and inflammation,which can affect the longevity of the implant and human health.For the sake of human health and the longevity of implants,it is essential to study the frictional and wear properties of biomedical metallic materials.The present review summarizes the current research on the frictional and wear properties of biomedical metallic materials in recent years,as well as the methods and techniques to improve the frictional and wear properties of the materials.The significance of the present review lies in that it could provide momentus information for further investigation of the tribological properties of biomedical metallic materials.