The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational biology.One of the most cutting-edge and important applications of ML is its integration with...The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational biology.One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improve the sampling efficiency of the vast conformational space of large biomolecules.This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape.We first highlight the recent development of ML-aided enhanced sampling methods,including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential,or facilitate the exploration of the unsampled region of the energy landscape.Further,we review the development of autoencoder based methods that combine molecular simulations and deep learning to expand the search for protein conformations.Lastly,we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights.Collectively,this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.展开更多
●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patient...●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited.Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was performed.The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular features.Cluster 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior cataracts.Cluster 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual outcomes.This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.展开更多
Rational design of high-performance electrocatalysts for hydrogen evolution reaction(HER)is vital for future renewable energy systems.The incorporation of foreign metal ions into catalysts can be an effective approach...Rational design of high-performance electrocatalysts for hydrogen evolution reaction(HER)is vital for future renewable energy systems.The incorporation of foreign metal ions into catalysts can be an effective approach to optimize its performance.However,there is a lack of systematic theoretical studies to reveal the quantitative relationships at the electronic level.Here,we develop a multi-level screening methodology to search for highly stable and active dopants for CoP catalysts.The density functional theory(DFT)calculations and symbolic regression(SR)were performed to investigate the relationship between the adsorption free energy(ΔG_(H^(*)))and 10 electronic parameters.The mathematic formulas derived from SR indicate that the difference of work function(ΔΦ)between doped metal and the acceptor plays the most important role in regulatingΔG_(H^(*)),followed by the d-band center(d-BC)of doped system.The descriptor of HER can be expressed asΔG_(H^(*))=1.59×√|0.188ΔΦ+d BC+0.120|1/2-0.166 with a high determination coefficient(R^(2)=0.807).Consistent with the theoretical prediction,experimental results show that the Al-CoP delivers superior electrocatalytic HER activity with a low overpotential of75 m V to drive a current density of 10 mA cm^(-2),while the overpotentials for undoped CoP,Mo-CoP,and V-CoP are 206,134,and 83 m V,respectively.The current work proves that theΔΦis the most significant regulatory parameter ofΔG_(H^(*))for ion-doped electrocatalysts.This finding can drive the discovery of high-performance ion-doped electrocatalysts,which is crucial for electrocatalytic water splitting.展开更多
AIM:To explore the hotspots and frontiers of genetic research on pediatric cataracts.METHODS:Global publications from 2013 to 2022 related to genes in pediatric cataracts were extracted from the Web of Science Core Co...AIM:To explore the hotspots and frontiers of genetic research on pediatric cataracts.METHODS:Global publications from 2013 to 2022 related to genes in pediatric cataracts were extracted from the Web of Science Core Collection,and were analyzed in terms of the publication counts,countries,journals,authors,keywords,cited references,subject categories,and the underlying hotspots and frontiers.RESULTS:Totally 699 publications were included in the final analysis.The predominant actors were identified,with China(n=240)and PLoS One(n=33)being the most productive country and journal respectively.The research hotspots extracted from keywords were crystallin gene mutations,pathogenicity evaluation,phenotypes of ocular and neurodevelopmental abnormalities,genes encoding membrane proteins,and diagnosis of multisystemic disorders.The co-cited articles formed 10 clusters of research topics,including FYCO1(56 items),mutation screening(43 items),gap junction(29 items),the Warburg Micro syndrome(29 items),ephrin-A5(28 items),novel mutation(24 items),eye development and function(22 items),cholestanol(7 items),OCRL(6 items),and pathogenicity prediction(3 items).The research frontiers were FYCO1,ephrin-A5,and cholestanol.Cell biology showed the strongest bridging effects among different disciplines in the field(betweenness centrality=0.44).CONCLUSION:With the progress in next-generation sequencing and multidisciplinary collaboration,genetic research on pediatric cataracts broadens the knowledge scope of the crystalline lens,as well as other organs and systems,shedding light on the molecular mechanisms of systemic diseases.Cell biology may integrate multidisciplinary content to address cutting-edge issues in the field.展开更多
Background:Research on high myopia has gradually formed a complex network of knowledge,but a panorama of evolutionary trends is lacking.By conducting a scientometric analysis,we can gain a deeper understanding of the ...Background:Research on high myopia has gradually formed a complex network of knowledge,but a panorama of evolutionary trends is lacking.By conducting a scientometric analysis,we can gain a deeper understanding of the development and evolution of this field.Methods:The global literature on high myopia published from 2002 to 2021 was extracted from the Science Citation Index Expanded in the Web of Science Core Collection.Microsoft Excel,VOSviewer,and CiteSpace were used to analyse and visualize the bibliometric data.Publication-related information,including countries,journals,authors,citations,subject categories,and its’time trends,was analysed.Results:A total of 4,226 included publications showed an annually increasing trend during the past 20 years.The high myopia research hotspots were refractive error correction,epidemiology,ocular biometry,drug and laser treatment of myopic fundus lesions,and surgical treatment of myopic fundus lesions.Cocitation analysis showed that high myopia genetics and myopic fundus lesion research were the research frontiers.A total of 116 disciplines were involved in high myopia research.Ophthalmology(n=3,338)was the most dominant subject category.Engineering(betweenness centrality=0.65)was the discipline with the most obvious bridge role.Science&technology—other topics(burst years:2015–2021;strength=14.88)had the greatest strength as of 2021,which was the hottest subject category.Conclusions:High myopia genetics and myopic fundus lesion research showed a potential for breakthroughs.Medical-engineering cross-innovation is a cutting-edge technology trend.展开更多
A theoretical study on the structural dynamics of the temporal behavior of Bragg diffraction is presented and compared with experimental results obtained via ultrafast electron crystallography.In order to describe the...A theoretical study on the structural dynamics of the temporal behavior of Bragg diffraction is presented and compared with experimental results obtained via ultrafast electron crystallography.In order to describe the time-dependent lattices and calculate the Bragg diffraction intensity,we introduce the basic vector offset matrix,which can be used to quantify the shortening,lengthening and rotation of the three lattice vectors(i.e.,lattice deformation).Extensive simulations are performed to evaluate the four-dimensional electron crystallography model.The results elucidate the connection between structural deformations and changes in diffraction peaks,and sheds light on the quantitative analysis and comprehensive understanding of the structural dynamics.展开更多
BACKGROUND Advanced colorectal cancer(CRC) generally has poor outcomes and high mortality rates. Clarifying the molecular mechanisms underlying CRC progression is necessary to develop new diagnostic and therapeutic st...BACKGROUND Advanced colorectal cancer(CRC) generally has poor outcomes and high mortality rates. Clarifying the molecular mechanisms underlying CRC progression is necessary to develop new diagnostic and therapeutic strategies to improve CRC outcome and decrease mortality. Transcriptional factor Ⅲ A(GTF3A), an RNA polymerase Ⅲ transcriptional factor, is a critical driver of tumorgenesis and aggravates CRC cell growth.AIM To confirm whether GTF3A promotes CRC progression by regulating the expression of cystatin A(Csta) gene and investigate whether GTF3A can serve as a prognostic biomarker and therapeutic target for patients with CRC.METHODS Human tissue microarrays containing 90 pairs of CRC tissues and adjacent nontumor tissues, and human tissue microarrays containing 20 pairs of CRC tissues,adjacent non-tumor tissues, and metastatic tissues were examined for GTF3A expression using immunohistochemistry. The survival rates of patients were analyzed. Short hairpin GTF3As and CSTAs were designed and packaged into the virus to block the expression of Gtf3a and Csta genes, respectively. In vivo tumor growth assays were performed to confirm whether GTF3A promotes CRC cell proliferation in vivo. Electrophoretic mobility shift assay and fluorescence in situ hybridization assay were used to detect the interaction of GTF3A with Csta,whereas luciferase activity assay was used to evaluate the expression of the Gtf3a and Csta genes. RNA-Sequencing(RNA-Seq) and data analyses were used to screen for target genes of GTF3A.RESULTS The expression of GTF3A was higher in CRC tissues and lymph node metastatic tissues than in the adjacent normal tissues. GTF3A was associated with CRC prognosis, and knockdown of the Gtf3a gene impaired CRC cell proliferation, invasion, and motility in vitro and in vivo. Moreover, RNASeq analysis revealed that GTF3A might upregulate the expression of Csta, whereas the luciferase activity assay showed that GTF3A bound to the promoter of Csta gene and increased Csta transcription. Furthermore, CSTA regulated the expression of epithelial-mesenchymal transition(EMT) markers.CONCLUSION GTF3A increases CSTA expression by binding to the Csta promoter, and increased CSTA level promotes CRC progression by regulating the EMT. Inhibition of GTF3A prevents CRC progression. Therefore, GTF3A is a potential novel therapeutic target and biomarker for CRC.展开更多
Chinese tallow tree (Triadica sebifera (L.) Small, Sapium sebiferum (L.) Roxb) is an invasive species that is replacing native ecosystems in areas of eastern Texas. It is imperative that the spatial pattern of the spr...Chinese tallow tree (Triadica sebifera (L.) Small, Sapium sebiferum (L.) Roxb) is an invasive species that is replacing native ecosystems in areas of eastern Texas. It is imperative that the spatial pattern of the spread of this species be identified, as well as causal mechanisms. To that end, we seek to determine factors that contribute to the spread of Chinese tallow using classification and regression tree (CART) and logistic regression. We also attempt to identify current locations and spread rates across eastern Texas using Forest Inventory Analysis (FIA) data within major forest types. Distance to formerly infested plots and roads, slope, and disturbances (natural and anthropogenic) were identified as major (either facilitating or impeding) factors for the spread of Chinese tallow across the landscape. The highest probability of occurrence and spread rate of Chinese tallow were found in the oak/ gum/cypress forest type. Continued disturbance, from harvest events or natural disasters will allow the species to continue to spread throughout the region and could threaten overall forest productivity. We also discuss some implications of the continued spread of Chinese tallow on forest management. Forest managers could benefit from this analysis and use it as a guide for monitoring forest types with the highest risk of invasion.展开更多
Screw conveyors,widely used devices for transporting bulk materials,play an irreplaceable role in the modern industrial system.Despite of their traditional advantages,designers of screw conveyors still heavily rely on...Screw conveyors,widely used devices for transporting bulk materials,play an irreplaceable role in the modern industrial system.Despite of their traditional advantages,designers of screw conveyors still heavily rely on their own country's experiments and standards,which are closely related to empirical data.Therefore,the same conveying task often results in different designs.This work aims to compare the design standards of screw conveyors in China,Germany and the USA.Based on related standards acquired from renowned associations in the three countries,the similarities and particularities of these design guidances are compared.With preforming the geometrical and operational designs for horizon-tal,slightly inclined and vertical conveyance of three representative bulk solids(barley,lignite,sand),the advantages and disadvantages of these semi-empirical designs are comprehensively presented.Fur-thermore,the potential influence of empirical coefficients,which are not explicitly documented,are extensively discussed.By analysing all outcomes,the compatibility and applicability of each standard are qualitatively assessed.展开更多
An ultra-sensitive and highly selective parathion methyl(PM) detection method by surface plasmon resonance(SPR) combined with molecularly imprinted films(MIF) was developed. The PM-imprinted film was prepared by therm...An ultra-sensitive and highly selective parathion methyl(PM) detection method by surface plasmon resonance(SPR) combined with molecularly imprinted films(MIF) was developed. The PM-imprinted film was prepared by thermo initiated polymerization on the bare Au surface of an SPR sensor chip.Template PM molecules were quickly removed by an organic solution of acetonitrile/acetic acid(9:1,v/v), causing a shift of 0.58 in SPR angle. In the concentrations range of 10à13–10à10mol/L, the refractive index showed a gradual increase with higher concentrations of template PM and the changes of SPR angles were linear with the negative logarithm of PM concentrations. In the experiment, the minimum detectable concentration was 10à13mol/L. The selectivity of the thin PM-imprinted film against diuron,tetrachlorvinphose and fenitrothion was examined, but no observable binding was detected. The results in the experiment suggested that the MIF had the advantages of high sensitivity and selectivity.展开更多
To the Editor:Corneal alkali burns(CABs)have been a difficult problem in clinical treatment for a long time.In severe cases,blindness occurs;hence,research on the repair mechanism underlying corneal injury is particul...To the Editor:Corneal alkali burns(CABs)have been a difficult problem in clinical treatment for a long time.In severe cases,blindness occurs;hence,research on the repair mechanism underlying corneal injury is particularly important to identify potential therapeutic targets.Alkali-induced corneal injuries often trigger aggressive aseptic inflammatory responses,which are key to autoimmune responses.[1]However,Nod-like receptor protein 3(NLRP3)inflammasomes play an important role in aseptic inflammation.[2]Under stimuli,such as infection or stress,the activated NLRP3 inflammasome not only processes procaspase-1 into mature caspase-1 but also further promotes the maturation and release of interleukin(IL)-1βand IL-18.[3]Taurine(Tau)is widely distributed in ocular structures and is an immune regulator.Tau can maintain the stability of the corneal epithelium and improve the survival rate of corneal epithelial cells through antioxidant effects.[4]The purpose of this study was to investigate the effect of Tau eye drops on CAB and elucidate the mechanism underlying corneal inflammatory responses.展开更多
基金Project supported by the National Key Research and Development Program of China(Grant No.2023YFF1204402)the National Natural Science Foundation of China(Grant Nos.12074079 and 12374208)+1 种基金the Natural Science Foundation of Shanghai(Grant No.22ZR1406800)the China Postdoctoral Science Foundation(Grant No.2022M720815).
文摘The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational biology.One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improve the sampling efficiency of the vast conformational space of large biomolecules.This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape.We first highlight the recent development of ML-aided enhanced sampling methods,including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential,or facilitate the exploration of the unsampled region of the energy landscape.Further,we review the development of autoencoder based methods that combine molecular simulations and deep learning to expand the search for protein conformations.Lastly,we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights.Collectively,this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.
基金Supported by the Municipal Government and School(Hospital)Joint Funding Programme of Guangzhou(No.2023A03J0174,No.2023A03J0188)the State Key Laboratories’Youth Program of China(No.83000-32030003).
文摘●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited.Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was performed.The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular features.Cluster 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior cataracts.Cluster 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual outcomes.This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.
基金Financial support from the National Natural Science Foundation of China(21676216)the Special project of Shaanxi Provincial Education Department(20JC034)+1 种基金GHfund B(202202022563)Hefei Advanced Computing Center。
文摘Rational design of high-performance electrocatalysts for hydrogen evolution reaction(HER)is vital for future renewable energy systems.The incorporation of foreign metal ions into catalysts can be an effective approach to optimize its performance.However,there is a lack of systematic theoretical studies to reveal the quantitative relationships at the electronic level.Here,we develop a multi-level screening methodology to search for highly stable and active dopants for CoP catalysts.The density functional theory(DFT)calculations and symbolic regression(SR)were performed to investigate the relationship between the adsorption free energy(ΔG_(H^(*)))and 10 electronic parameters.The mathematic formulas derived from SR indicate that the difference of work function(ΔΦ)between doped metal and the acceptor plays the most important role in regulatingΔG_(H^(*)),followed by the d-band center(d-BC)of doped system.The descriptor of HER can be expressed asΔG_(H^(*))=1.59×√|0.188ΔΦ+d BC+0.120|1/2-0.166 with a high determination coefficient(R^(2)=0.807).Consistent with the theoretical prediction,experimental results show that the Al-CoP delivers superior electrocatalytic HER activity with a low overpotential of75 m V to drive a current density of 10 mA cm^(-2),while the overpotentials for undoped CoP,Mo-CoP,and V-CoP are 206,134,and 83 m V,respectively.The current work proves that theΔΦis the most significant regulatory parameter ofΔG_(H^(*))for ion-doped electrocatalysts.This finding can drive the discovery of high-performance ion-doped electrocatalysts,which is crucial for electrocatalytic water splitting.
基金Supported by the National Natural Science Foundation of China(No.81900841)the Science and Technology Program of Guangzhou,China(No.202201011815)+3 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515011181)the Teaching Reform Research Program of Sun Yat-sen University(No.JX3030604024)the Youth Project of State Key Laboratory of Ophthalmology(No.2021QN02)the Construction Project of High-Level Hospitals in Guangdong Province(No.303020102).
文摘AIM:To explore the hotspots and frontiers of genetic research on pediatric cataracts.METHODS:Global publications from 2013 to 2022 related to genes in pediatric cataracts were extracted from the Web of Science Core Collection,and were analyzed in terms of the publication counts,countries,journals,authors,keywords,cited references,subject categories,and the underlying hotspots and frontiers.RESULTS:Totally 699 publications were included in the final analysis.The predominant actors were identified,with China(n=240)and PLoS One(n=33)being the most productive country and journal respectively.The research hotspots extracted from keywords were crystallin gene mutations,pathogenicity evaluation,phenotypes of ocular and neurodevelopmental abnormalities,genes encoding membrane proteins,and diagnosis of multisystemic disorders.The co-cited articles formed 10 clusters of research topics,including FYCO1(56 items),mutation screening(43 items),gap junction(29 items),the Warburg Micro syndrome(29 items),ephrin-A5(28 items),novel mutation(24 items),eye development and function(22 items),cholestanol(7 items),OCRL(6 items),and pathogenicity prediction(3 items).The research frontiers were FYCO1,ephrin-A5,and cholestanol.Cell biology showed the strongest bridging effects among different disciplines in the field(betweenness centrality=0.44).CONCLUSION:With the progress in next-generation sequencing and multidisciplinary collaboration,genetic research on pediatric cataracts broadens the knowledge scope of the crystalline lens,as well as other organs and systems,shedding light on the molecular mechanisms of systemic diseases.Cell biology may integrate multidisciplinary content to address cutting-edge issues in the field.
基金supported by the National Natural Science Foundation of China(No.81873675)the Science and Technology Program of Guangzhou,China(No.202201011815)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515011181)the Teaching Reform Research Program of Sun Yat-sen University(No.JX3030604024)the Youth Project of State Key Laboratory of Ophthalmology(No.2022QN03).
文摘Background:Research on high myopia has gradually formed a complex network of knowledge,but a panorama of evolutionary trends is lacking.By conducting a scientometric analysis,we can gain a deeper understanding of the development and evolution of this field.Methods:The global literature on high myopia published from 2002 to 2021 was extracted from the Science Citation Index Expanded in the Web of Science Core Collection.Microsoft Excel,VOSviewer,and CiteSpace were used to analyse and visualize the bibliometric data.Publication-related information,including countries,journals,authors,citations,subject categories,and its’time trends,was analysed.Results:A total of 4,226 included publications showed an annually increasing trend during the past 20 years.The high myopia research hotspots were refractive error correction,epidemiology,ocular biometry,drug and laser treatment of myopic fundus lesions,and surgical treatment of myopic fundus lesions.Cocitation analysis showed that high myopia genetics and myopic fundus lesion research were the research frontiers.A total of 116 disciplines were involved in high myopia research.Ophthalmology(n=3,338)was the most dominant subject category.Engineering(betweenness centrality=0.65)was the discipline with the most obvious bridge role.Science&technology—other topics(burst years:2015–2021;strength=14.88)had the greatest strength as of 2021,which was the hottest subject category.Conclusions:High myopia genetics and myopic fundus lesion research showed a potential for breakthroughs.Medical-engineering cross-innovation is a cutting-edge technology trend.
基金Supported by the National Key Research and Development Program of China under Grant Nos.2016YFA0300303,2017YFA0504703,and 2017YFA0302904the National Basic Research Program of China under Grant No.2015CB921304+2 种基金the National Natural Science Foundation of China under Grant Nos.11604372,11474323,11774391,11774403,and 61575085the Strategic Priority Research Program(B)of the Chinese Academy of Sciences under Grant No.XDB25000000the Scientific Instrument Developing Project of the Chinese Academy of Sciences under Grant No.ZDKYYQ20170002。
文摘A theoretical study on the structural dynamics of the temporal behavior of Bragg diffraction is presented and compared with experimental results obtained via ultrafast electron crystallography.In order to describe the time-dependent lattices and calculate the Bragg diffraction intensity,we introduce the basic vector offset matrix,which can be used to quantify the shortening,lengthening and rotation of the three lattice vectors(i.e.,lattice deformation).Extensive simulations are performed to evaluate the four-dimensional electron crystallography model.The results elucidate the connection between structural deformations and changes in diffraction peaks,and sheds light on the quantitative analysis and comprehensive understanding of the structural dynamics.
基金Supported by the National Natural Science Foundation of China,No.81872226Changsha Science and Technology Project,No.2019TP1046the Research Projects of Hunan Health Commission,No.B2019084.
文摘BACKGROUND Advanced colorectal cancer(CRC) generally has poor outcomes and high mortality rates. Clarifying the molecular mechanisms underlying CRC progression is necessary to develop new diagnostic and therapeutic strategies to improve CRC outcome and decrease mortality. Transcriptional factor Ⅲ A(GTF3A), an RNA polymerase Ⅲ transcriptional factor, is a critical driver of tumorgenesis and aggravates CRC cell growth.AIM To confirm whether GTF3A promotes CRC progression by regulating the expression of cystatin A(Csta) gene and investigate whether GTF3A can serve as a prognostic biomarker and therapeutic target for patients with CRC.METHODS Human tissue microarrays containing 90 pairs of CRC tissues and adjacent nontumor tissues, and human tissue microarrays containing 20 pairs of CRC tissues,adjacent non-tumor tissues, and metastatic tissues were examined for GTF3A expression using immunohistochemistry. The survival rates of patients were analyzed. Short hairpin GTF3As and CSTAs were designed and packaged into the virus to block the expression of Gtf3a and Csta genes, respectively. In vivo tumor growth assays were performed to confirm whether GTF3A promotes CRC cell proliferation in vivo. Electrophoretic mobility shift assay and fluorescence in situ hybridization assay were used to detect the interaction of GTF3A with Csta,whereas luciferase activity assay was used to evaluate the expression of the Gtf3a and Csta genes. RNA-Sequencing(RNA-Seq) and data analyses were used to screen for target genes of GTF3A.RESULTS The expression of GTF3A was higher in CRC tissues and lymph node metastatic tissues than in the adjacent normal tissues. GTF3A was associated with CRC prognosis, and knockdown of the Gtf3a gene impaired CRC cell proliferation, invasion, and motility in vitro and in vivo. Moreover, RNASeq analysis revealed that GTF3A might upregulate the expression of Csta, whereas the luciferase activity assay showed that GTF3A bound to the promoter of Csta gene and increased Csta transcription. Furthermore, CSTA regulated the expression of epithelial-mesenchymal transition(EMT) markers.CONCLUSION GTF3A increases CSTA expression by binding to the Csta promoter, and increased CSTA level promotes CRC progression by regulating the EMT. Inhibition of GTF3A prevents CRC progression. Therefore, GTF3A is a potential novel therapeutic target and biomarker for CRC.
文摘Chinese tallow tree (Triadica sebifera (L.) Small, Sapium sebiferum (L.) Roxb) is an invasive species that is replacing native ecosystems in areas of eastern Texas. It is imperative that the spatial pattern of the spread of this species be identified, as well as causal mechanisms. To that end, we seek to determine factors that contribute to the spread of Chinese tallow using classification and regression tree (CART) and logistic regression. We also attempt to identify current locations and spread rates across eastern Texas using Forest Inventory Analysis (FIA) data within major forest types. Distance to formerly infested plots and roads, slope, and disturbances (natural and anthropogenic) were identified as major (either facilitating or impeding) factors for the spread of Chinese tallow across the landscape. The highest probability of occurrence and spread rate of Chinese tallow were found in the oak/ gum/cypress forest type. Continued disturbance, from harvest events or natural disasters will allow the species to continue to spread throughout the region and could threaten overall forest productivity. We also discuss some implications of the continued spread of Chinese tallow on forest management. Forest managers could benefit from this analysis and use it as a guide for monitoring forest types with the highest risk of invasion.
基金This project has received funding from the European Union's Horizon 2020 Program(H2020/2014-2020),under grant agreement no.654446.
文摘Screw conveyors,widely used devices for transporting bulk materials,play an irreplaceable role in the modern industrial system.Despite of their traditional advantages,designers of screw conveyors still heavily rely on their own country's experiments and standards,which are closely related to empirical data.Therefore,the same conveying task often results in different designs.This work aims to compare the design standards of screw conveyors in China,Germany and the USA.Based on related standards acquired from renowned associations in the three countries,the similarities and particularities of these design guidances are compared.With preforming the geometrical and operational designs for horizon-tal,slightly inclined and vertical conveyance of three representative bulk solids(barley,lignite,sand),the advantages and disadvantages of these semi-empirical designs are comprehensively presented.Fur-thermore,the potential influence of empirical coefficients,which are not explicitly documented,are extensively discussed.By analysing all outcomes,the compatibility and applicability of each standard are qualitatively assessed.
基金supported by the National Natural Science Foundation of China (No.20771015)the National ‘‘111’’ Project of China’s Higher Education (No.B07012)
文摘An ultra-sensitive and highly selective parathion methyl(PM) detection method by surface plasmon resonance(SPR) combined with molecularly imprinted films(MIF) was developed. The PM-imprinted film was prepared by thermo initiated polymerization on the bare Au surface of an SPR sensor chip.Template PM molecules were quickly removed by an organic solution of acetonitrile/acetic acid(9:1,v/v), causing a shift of 0.58 in SPR angle. In the concentrations range of 10à13–10à10mol/L, the refractive index showed a gradual increase with higher concentrations of template PM and the changes of SPR angles were linear with the negative logarithm of PM concentrations. In the experiment, the minimum detectable concentration was 10à13mol/L. The selectivity of the thin PM-imprinted film against diuron,tetrachlorvinphose and fenitrothion was examined, but no observable binding was detected. The results in the experiment suggested that the MIF had the advantages of high sensitivity and selectivity.
基金supported by grants from the Science and Technology Plan Project of Xiangyang(No.2020YL40)the Innovative Research Program for Graduates of Hubei University of Medicine(YC2020024)。
文摘To the Editor:Corneal alkali burns(CABs)have been a difficult problem in clinical treatment for a long time.In severe cases,blindness occurs;hence,research on the repair mechanism underlying corneal injury is particularly important to identify potential therapeutic targets.Alkali-induced corneal injuries often trigger aggressive aseptic inflammatory responses,which are key to autoimmune responses.[1]However,Nod-like receptor protein 3(NLRP3)inflammasomes play an important role in aseptic inflammation.[2]Under stimuli,such as infection or stress,the activated NLRP3 inflammasome not only processes procaspase-1 into mature caspase-1 but also further promotes the maturation and release of interleukin(IL)-1βand IL-18.[3]Taurine(Tau)is widely distributed in ocular structures and is an immune regulator.Tau can maintain the stability of the corneal epithelium and improve the survival rate of corneal epithelial cells through antioxidant effects.[4]The purpose of this study was to investigate the effect of Tau eye drops on CAB and elucidate the mechanism underlying corneal inflammatory responses.
