The exercise recommendation system is emerging as a promising application in online learning scenarios,providing personalized recommendations to assist students with explicit learning directions.Existing solutions gen...The exercise recommendation system is emerging as a promising application in online learning scenarios,providing personalized recommendations to assist students with explicit learning directions.Existing solutions generally follow a collaborative filtering paradigm,while the implicit connections between students(exercises)have been largely ignored.In this study,we aim to propose an exercise recommendation paradigm that can reveal the latent connections between student-student(exercise-exercise).Specifically,a new framework was proposed,namely personalized exercise recommendation with student and exercise portraits(PERP).It consists of three sequential and interdependent modules:Collaborative student exercise graph(CSEG)construction,joint random walk,and recommendation list optimization.Technically,CSEG is created as a unified heterogeneous graph with students’response behaviors and student(exercise)relationships.Then,a joint random walk to take full advantage of the spectral properties of nearly uncoupled Markov chains is performed on CSEG,which allows for full exploration of both similar exercises that students have finished and connections between students(exercises)with similar portraits.Finally,we propose to optimize the recommendation list to obtain different exercise suggestions.After analyses of two public datasets,the results demonstrated that PERP can satisfy novelty,accuracy,and diversity.展开更多
A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this...A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats(cold water swimming for 3 minutes at 4℃) spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~+ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.展开更多
In the present work,the interaction mechanism of specific polyelectrolyte multilayers(PEMs),fabricated by layer-by-layer deposition of polydiallyldimethylammonium chloride(PDDA)and poly(sodium 4-styrenesulfonate)(PSS)...In the present work,the interaction mechanism of specific polyelectrolyte multilayers(PEMs),fabricated by layer-by-layer deposition of polydiallyldimethylammonium chloride(PDDA)and poly(sodium 4-styrenesulfonate)(PSS),is studied using atomic force microscopy.The underwater oil-repellency of PS S-capped PEMs was further explored by measuring the interaction forces between tetradecane droplets and PEMs-coated silica substrates under various salinities.The force curves were analyzed following the Stokes-Reynolds-Young-Laplace theoretical model.Desirable consistency was achieved between the experimental and theoretical calculations at low NaCl concentrations(0.1 mM and 1 mM);however,underestimation of the attractive force was found as the NaCl concentration increases to moderate(10 mM)and high(100 mM)levels.Discrepancy analyses and incorporated features toward a reduced surface charge density were considered based on the previous findings of the orientation of anionic benzenesulfonate moieties(Liu et al.in Angew Chem Int Ed 54(16):4851-4856,2015.https://doi.org/10.1002/anie.201411992).Short-range steric hindrance interactions were further introduced to simulate"brush"effect stemming from nanoscale surface roughness.It is demonstrated in our work that the PSS-capped PEMs remains a stable underwater lipophobicity against high salinity,which renders it potential application in surface wetting modification and anti-fouling.展开更多
Background::Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),such as erlotinib and gefitinib,are widely used to treat non-small cell lung cancer(NSCLC).However,acquired resistance is unavoidable,...Background::Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),such as erlotinib and gefitinib,are widely used to treat non-small cell lung cancer(NSCLC).However,acquired resistance is unavoidable,impairing the anti-tumor effects of EGFR-TKIs.It is reported that histone deacetylase(HDAC)inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy.However,whether the HDAC inhibitor suberoylanilide hydroxamic acid(SAHA)can overcome erlotinib-acquired resistance is not fully clear.Methods::An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures.NSCLC cells were co-cultured with SAHA,erlotinib,or their combination,and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting.Finally,the expression of phosphatase and tensin homolog deleted on chromosome 10(PTEN)was assessed by western blotting.Results::The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line.PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells,and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells.Furthermore,treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.Conclusions::PTEN deletion is closely related to acquired resistance to EGFR-TKIs,and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy.SAHA enhances the suppressive effects of erlotinib in lung cancer cells,increasing cellular apoptosis and PTEN expression.SAHA can be a potential adjuvant to erlotinib treatment,and thus,can improve the efficacy of NSCLC therapy.展开更多
A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spect...A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.展开更多
A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial agents.Bioactive evaluation in vitro showed that compound 3f exhibited equipotent or superior ant...A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial agents.Bioactive evaluation in vitro showed that compound 3f exhibited equipotent or superior anti-methicillin-resistant Staphylococcus aureus(anti-MRSA) and anti-S. cerevisiae efficiencies(minimal inhibitory concentration(MIC)=2 μg/mL) to clinical drugs,and the combinations with antibacterial or antifungal drugs enhanced the antimicrobial efficiency. Highly active molecule 3f showed low propensity for bacteria to develop resistance, and the preliminary action mechanism studies demonstrated that 3f was membrane-active, but had no significant intercalation towards MRSA DNA. The computational study on 3f reasonably explained its high antimicrobial activity. Experimental data revealed that ground-state 3f-HSA complexes were formed mainly through hydrophobic interactions and hydrogen bonds with a spontaneous process, and the non-radioactive energy transfer from HSA to 3f occurred beyond F鰎ster resonance energy transfer theory. The participation of metal ions in 3f-HSA supramolucular system could increase the concentration of free compound 3f, and shorten its storage time and half-life in the blood to improve the maximum antimicrobial efficacy.展开更多
Study of stable liquid crystal(LC)microdroplets is of great significance for LC dynamics in con fined space or at topological surface.However,the fabrication of LC microdroplets with diverse shape without ionic gelati...Study of stable liquid crystal(LC)microdroplets is of great significance for LC dynamics in con fined space or at topological surface.However,the fabrication of LC microdroplets with diverse shape without ionic gelati on agents still remai ns challe nging due to the fluid instability.Here,we utilize the microfluidic tech no logy to prepare graphe ne oxide(GO)LC microdroplets with various morphologies based on the anomalous rheological property of GO aqueous dispersion.Different from LC of one-dimensional polymer,LC containing two-dimensional GO sheets exhibits considerable viscoelasticity and weak extensibility,resulting from the planar molecular conformation and the absence of intermolecular entangleme nts.The low exte risibility ensures that GO aqueous suspension is discretized into mono dispersed microdroplets rather than thin thread in the microfluidic channels.The large viscoelasticity and ultra-1 ong relaxation time of GO LC enable the diverse stable morphologies of microdroplets.The droplet morphology is well con trolled from sphere to teardrop by modulati ng the competition between GO viscoelasticity and in terfacial ten sion.The two-dimensional GO LC featuri ng unique rheological property provides a novel system for the microfluidic field,and corresponding topological stability enriches the LC dyn amics and ope ns a new pathway for desig ning graphe ne-based materials.展开更多
A series of novel naphthalimide-derived metronidazoles as new type of antimicrobial agents were for the first time designed, synthesized and characterized by NMR, IR and HRMS spectra. Experimental results revealed tha...A series of novel naphthalimide-derived metronidazoles as new type of antimicrobial agents were for the first time designed, synthesized and characterized by NMR, IR and HRMS spectra. Experimental results revealed that most of them displayed moderate to good antibacterial activity towards Gram-positive and negative bacteria. Especially, compound 7b was able to not only exhibit effective inhibition towards the growth of P. vulgaris(MIC = 0.002 mmol/m L) and S. dysenteriae(MIC = 0.01 mmol/m L), but also have rapidly killing effect and prevent the development of bacterial resistance. Further research revealed that the highly active molecule 7b could not only intercalate into calf thymus DNA to form a steady supramolecular complex and thus might block DNA replication to exert the powerful bioactivities, but also be effectively transported by human serum albumin(HSA) via the formation of the 1:1supramolecular complex, in which hydrogen bonds and hydrophobic effect played important roles in the association of compound 7b with HSA. Molecular docking indicated that the supramolecular interactions between 7b and topoisomerase II were driven by hydrogen bonds.展开更多
基金supported by the Industrial Support Project of Gansu Colleges under Grant No.2022CYZC-11Gansu Natural Science Foundation Project under Grant No.21JR7RA114+1 种基金National Natural Science Foundation of China under Grants No.622760736,No.1762078,and No.61363058Northwest Normal University Teachers Research Capacity Promotion Plan under Grant No.NWNU-LKQN2019-2.
文摘The exercise recommendation system is emerging as a promising application in online learning scenarios,providing personalized recommendations to assist students with explicit learning directions.Existing solutions generally follow a collaborative filtering paradigm,while the implicit connections between students(exercises)have been largely ignored.In this study,we aim to propose an exercise recommendation paradigm that can reveal the latent connections between student-student(exercise-exercise).Specifically,a new framework was proposed,namely personalized exercise recommendation with student and exercise portraits(PERP).It consists of three sequential and interdependent modules:Collaborative student exercise graph(CSEG)construction,joint random walk,and recommendation list optimization.Technically,CSEG is created as a unified heterogeneous graph with students’response behaviors and student(exercise)relationships.Then,a joint random walk to take full advantage of the spectral properties of nearly uncoupled Markov chains is performed on CSEG,which allows for full exploration of both similar exercises that students have finished and connections between students(exercises)with similar portraits.Finally,we propose to optimize the recommendation list to obtain different exercise suggestions.After analyses of two public datasets,the results demonstrated that PERP can satisfy novelty,accuracy,and diversity.
基金supported by a grant from the Incubation Project of Natural Science Foundation of Tianjin Medical University General Hospital in China,No.303071901401the Natural Science Foundation of Tianjin of China,No.13JCZDJC30800the National Natural Science Foundation of China,No.81271361 and 81330029
文摘A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats(cold water swimming for 3 minutes at 4℃) spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~+ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.
基金the National Natural Science Foundation of China(51774303,51422406,51534007)the National Science and Technology Specific Project(2016ZX05028-004001)111 Project(B18054)for providing support for this research。
文摘In the present work,the interaction mechanism of specific polyelectrolyte multilayers(PEMs),fabricated by layer-by-layer deposition of polydiallyldimethylammonium chloride(PDDA)and poly(sodium 4-styrenesulfonate)(PSS),is studied using atomic force microscopy.The underwater oil-repellency of PS S-capped PEMs was further explored by measuring the interaction forces between tetradecane droplets and PEMs-coated silica substrates under various salinities.The force curves were analyzed following the Stokes-Reynolds-Young-Laplace theoretical model.Desirable consistency was achieved between the experimental and theoretical calculations at low NaCl concentrations(0.1 mM and 1 mM);however,underestimation of the attractive force was found as the NaCl concentration increases to moderate(10 mM)and high(100 mM)levels.Discrepancy analyses and incorporated features toward a reduced surface charge density were considered based on the previous findings of the orientation of anionic benzenesulfonate moieties(Liu et al.in Angew Chem Int Ed 54(16):4851-4856,2015.https://doi.org/10.1002/anie.201411992).Short-range steric hindrance interactions were further introduced to simulate"brush"effect stemming from nanoscale surface roughness.It is demonstrated in our work that the PSS-capped PEMs remains a stable underwater lipophobicity against high salinity,which renders it potential application in surface wetting modification and anti-fouling.
文摘Background::Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),such as erlotinib and gefitinib,are widely used to treat non-small cell lung cancer(NSCLC).However,acquired resistance is unavoidable,impairing the anti-tumor effects of EGFR-TKIs.It is reported that histone deacetylase(HDAC)inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy.However,whether the HDAC inhibitor suberoylanilide hydroxamic acid(SAHA)can overcome erlotinib-acquired resistance is not fully clear.Methods::An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures.NSCLC cells were co-cultured with SAHA,erlotinib,or their combination,and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting.Finally,the expression of phosphatase and tensin homolog deleted on chromosome 10(PTEN)was assessed by western blotting.Results::The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line.PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells,and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells.Furthermore,treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.Conclusions::PTEN deletion is closely related to acquired resistance to EGFR-TKIs,and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy.SAHA enhances the suppressive effects of erlotinib in lung cancer cells,increasing cellular apoptosis and PTEN expression.SAHA can be a potential adjuvant to erlotinib treatment,and thus,can improve the efficacy of NSCLC therapy.
基金supported by the National Natural Science Foundation of China(21672173,21372186)Research Fund for International Young Scientists from International(Regional)Cooperation and Exchange Program of NSFC(81650110529)+3 种基金Chongqing Special Foundation for Postdoctoral Research Proposal(Xm2016039,Xm2017185)Program for Overseas Young Talents from State Administration of Foreign Experts Affairs,China(WQ2017XNDX047)the Doctoral Fund of Southwest University(SWU111075)the Research Funds for the Central Universities(XDJK2017B015)
文摘A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.
基金supported by the National Natural Science Foundation of China(21672173,21372186)Research Fund for International Young Scientists from International(Regional)Cooperation and Exchange Program(81350110523)+1 种基金Chongqing Special Foundation for Postdoctoral Research Proposal(Xm2014127,Xm2016039)Fundamental Research Funds for the Central Universities(XDJK2016E059)
文摘A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial agents.Bioactive evaluation in vitro showed that compound 3f exhibited equipotent or superior anti-methicillin-resistant Staphylococcus aureus(anti-MRSA) and anti-S. cerevisiae efficiencies(minimal inhibitory concentration(MIC)=2 μg/mL) to clinical drugs,and the combinations with antibacterial or antifungal drugs enhanced the antimicrobial efficiency. Highly active molecule 3f showed low propensity for bacteria to develop resistance, and the preliminary action mechanism studies demonstrated that 3f was membrane-active, but had no significant intercalation towards MRSA DNA. The computational study on 3f reasonably explained its high antimicrobial activity. Experimental data revealed that ground-state 3f-HSA complexes were formed mainly through hydrophobic interactions and hydrogen bonds with a spontaneous process, and the non-radioactive energy transfer from HSA to 3f occurred beyond F鰎ster resonance energy transfer theory. The participation of metal ions in 3f-HSA supramolucular system could increase the concentration of free compound 3f, and shorten its storage time and half-life in the blood to improve the maximum antimicrobial efficacy.
基金by the National Natural Science Foundation of China(Nos.52090030,51533008,51703194,51973191,51873191 and 51803177)National Key R&D Program of China(No.2016YFA0200200),Hundred Talents Program of Zhejiang University(No.188020*194231701/113),Key Research and Development Plan of Zhejiang Province(2018C01049)+1 种基金the Fundamental Research Funds for the Central Universities(No.K20200060)Key Laboratory of Novel Adsorpti on and Separati on Materials and Applicatio n Technology of Zhejiang Province(No.512301-121502).
文摘Study of stable liquid crystal(LC)microdroplets is of great significance for LC dynamics in con fined space or at topological surface.However,the fabrication of LC microdroplets with diverse shape without ionic gelati on agents still remai ns challe nging due to the fluid instability.Here,we utilize the microfluidic tech no logy to prepare graphe ne oxide(GO)LC microdroplets with various morphologies based on the anomalous rheological property of GO aqueous dispersion.Different from LC of one-dimensional polymer,LC containing two-dimensional GO sheets exhibits considerable viscoelasticity and weak extensibility,resulting from the planar molecular conformation and the absence of intermolecular entangleme nts.The low exte risibility ensures that GO aqueous suspension is discretized into mono dispersed microdroplets rather than thin thread in the microfluidic channels.The large viscoelasticity and ultra-1 ong relaxation time of GO LC enable the diverse stable morphologies of microdroplets.The droplet morphology is well con trolled from sphere to teardrop by modulati ng the competition between GO viscoelasticity and in terfacial ten sion.The two-dimensional GO LC featuri ng unique rheological property provides a novel system for the microfluidic field,and corresponding topological stability enriches the LC dyn amics and ope ns a new pathway for desig ning graphe ne-based materials.
基金partially supported by National Natural Science Foundation of China(Nos.21372186,21672173)the Research Fund for International Young Scientists from International(Regional)Cooperation and Exchange Program(No.81650110529)Chongqing Special Foundation for Postdoctoral Research Proposal(No.Xm2016039)
文摘A series of novel naphthalimide-derived metronidazoles as new type of antimicrobial agents were for the first time designed, synthesized and characterized by NMR, IR and HRMS spectra. Experimental results revealed that most of them displayed moderate to good antibacterial activity towards Gram-positive and negative bacteria. Especially, compound 7b was able to not only exhibit effective inhibition towards the growth of P. vulgaris(MIC = 0.002 mmol/m L) and S. dysenteriae(MIC = 0.01 mmol/m L), but also have rapidly killing effect and prevent the development of bacterial resistance. Further research revealed that the highly active molecule 7b could not only intercalate into calf thymus DNA to form a steady supramolecular complex and thus might block DNA replication to exert the powerful bioactivities, but also be effectively transported by human serum albumin(HSA) via the formation of the 1:1supramolecular complex, in which hydrogen bonds and hydrophobic effect played important roles in the association of compound 7b with HSA. Molecular docking indicated that the supramolecular interactions between 7b and topoisomerase II were driven by hydrogen bonds.