With the emergence of pre-trained models,current neural networks are able to give task performance that is comparable to humans.However,we know little about the fundamental working mechanism of pre-trained models in w...With the emergence of pre-trained models,current neural networks are able to give task performance that is comparable to humans.However,we know little about the fundamental working mechanism of pre-trained models in which we do not know how they approach such performance and how the task is solved by the model.For example,given a task,human learns from easy to hard,whereas the model learns randomly.Undeniably,difficulty-insensitive learning leads to great success in natural language processing(NLP),but little attention has been paid to the effect of text difficulty in NLP.We propose a human learning matching index(HLM Index)to investigate the effect of text difficulty.Experiment results show:1)LSTM gives more human-like learning behavior than BERT.Additionally,UID-SuperLinear gives the best evaluation of text difficulty among four text difficulty criteria.Among nine tasks,some tasks’performance is related to text difficulty,whereas others are not.2)Model trained on easy data performs best in both easy and medium test data,whereas trained on hard data only performs well on hard test data.3)Train the model from easy to hard,leading to quicker convergence.展开更多
Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases s...Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory (Ml) and anti-inflammatory (M2) actions, and M2 macrophages have four subtypes. The co-action of Ml and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.展开更多
In recent years, the use of Schwann cell transplantation to repair peripheral nerve injury has attracted much attention. Animal-based studies show that the transplantation of Schwann cells in combination with nerve sc...In recent years, the use of Schwann cell transplantation to repair peripheral nerve injury has attracted much attention. Animal-based studies show that the transplantation of Schwann cells in combination with nerve scaffolds promotes the repair of injured peripheral nerves. Autologous Schwann cell transplantation in humans has been reported recently. This article reviews current methods for removing the extracellular matrix and analyzes its composition and function. The development and secretory products of Schwann cells are also reviewed. The methods for the repair of peripheral nerve injuries that use myelin and Schwann cell transplantation are assessed. This survey of the literature data shows that using a decellularized nerve conduit combined with Schwann cells represents an effective strategy for the treatment of peripheral nerve injury. This analysis provides a comprehensive basis on which to make clinical decisions for the repair of peripheral nerve injury.展开更多
A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors...A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors for regenerative success.Therefore,it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury.However,the identities of specific cytokines at various time points after sciatic nerve injury have not been determined.The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze,by protein microarray,the expression of different cytokines in the distal nerve after injury.Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines,e.g.,ciliary neurotrophic factor,were downregulated.The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines.Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways,Janus kinase/signal transducers and activators of transcription,phosphoinositide 3-kinase/protein kinase B,and notch signaling pathway.The cytokines involved in inflammation,immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes,cell-cell adhesion,and cell proliferation were up-regulated at 28 days after injury.Western blot analysis showed that the expression and changes of hepatocyte growth factor,glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis.The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration,as well as a basis for potential treatments of peripheral nerve injury.The study was approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital,China(approval number:2016-x9-07)in September 2016.展开更多
Sensory and motor nerve fibers of peripheral nerves have different anatomies and regeneration functions after injury. To gain a clear understanding of the biological processes behind these differences, we used a label...Sensory and motor nerve fibers of peripheral nerves have different anatomies and regeneration functions after injury. To gain a clear understanding of the biological processes behind these differences, we used a labeling technique termed isobaric tags for relative and absolute quantitation to investigate the protein profiles of spinal nerve tissues from Sprague-Dawley rats. In response to Wallerian degeneration, a total of 626 proteins were screened in sensory nerves, of which 368 were upregulated and 258 were downregulated. In addition, 637 proteins were screened in motor nerves, of which 372 were upregulated and 265 were downregulated. All identified proteins were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of bioinformatics, and the presence of several key proteins closely related to Wallerian degeneration were tested and verified using quantitative real-time polymerase chain reaction analyses. The differentially expressed proteins only identified in the sensory nerves were mainly relevant to various biological processes that included cell-cell adhesion, carbohydrate metabolic processes and cell adhesion, whereas differentially expressed proteins only identified in the motor nerves were mainly relevant to biological processes associated with the glycolytic process, cell redox homeostasis, and protein folding. In the aspect of the cellular component, the differentially expressed proteins in the sensory and motor nerves were commonly related to extracellular exosomes, the myelin sheath, and focal adhesion. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways. In conclusion, the present study screened differentially expressed proteins to reveal more about the differences and similarities between sensory and motor nerves during Wallerian degeneration. The present findings could provide a reference point for a future investigation into the differences between sensory and motor nerves in Wallerian degeneration and the characteristics of peripheral nerve regeneration. The study was approved by the Ethics Committee of the Chinese PLA General Hospital, China(approval No. 2016-x9-07) in September 2016.展开更多
Two new C21 steroidal glycosides,paniculatumosides H and I,together with four known ones were isolated from the roots of Cynanchum paniculatum(Bge.)Kitag.Their structures were identifed by spectroscopic methods includ...Two new C21 steroidal glycosides,paniculatumosides H and I,together with four known ones were isolated from the roots of Cynanchum paniculatum(Bge.)Kitag.Their structures were identifed by spectroscopic methods including extensive 1D and 2D NMR techniques.All compounds were subjected to detect the anti-tobacco mosaic virus(TMV)activities and their cytotoxities against three human tumor cell lines(SMMC-7721,MDA-MB-231 and A549).The results showed that compounds 1 and 5 exhibited potent protective activities against TMV,while 2,4 and 6 had moderate efects on the SMMC7721 cancer cells viability.展开更多
A new ent-abietane diterpernoid,named ebracteolata D(1),along with 11 known analogues,was isolated from the roots of Euphorbia ebracteolata Hayata.The structure of 1 was elucidated on the basis of spectroscopic analys...A new ent-abietane diterpernoid,named ebracteolata D(1),along with 11 known analogues,was isolated from the roots of Euphorbia ebracteolata Hayata.The structure of 1 was elucidated on the basis of spectroscopic analysis and molecular modeling.Cytotoxicity of compounds 1-12 was evaluated as well as the effect on the NF-κB pathway.Among them,compound 12,jolkinolide B,displayed broad inhibitory effects against proliferation of tumor cell lines.Mechanistic studies indicated that the compound 12 can inhibit TNF-αinduced NF-κB activation,thereby inducing tumor cell apoptosis.展开更多
In our previous study,we investigated the dynamic expression of cytokines in the distal nerve stumps after peripheral nerve injury using microarray analysis,which can characterize the dynamic expression of proteins.In...In our previous study,we investigated the dynamic expression of cytokines in the distal nerve stumps after peripheral nerve injury using microarray analysis,which can characterize the dynamic expression of proteins.In the present study,we used a rat model of right sciatic nerve transection to examine changes in the expression of cytokines at 1,7,14 and 28 days after injury using protein microarray analysis.Interleukins were increased in the distal nerve stumps at 1–14 days post nerve transection.However,growth factors and growth factor-related proteins were mainly upregulated in the proximal nerve stumps.The P-values of the inflammatory response,apoptotic response and cell-cell adhesion in the distal stumps were higher than those in the proximal nerve stumps,but the opposite was observed for angiogenesis.The number of cytokines related to axons in the distal stumps was greater than that in the proximal stumps,while the percentage of cytokines related to axons in the distal stumps was lower than that in the proximal nerve stumps.Visualization of the results revealed the specific expression patterns and differences in cytokines in and between the proximal and distal nerve stumps.Our findings offer potential therapeutic targets and should help advance the development of clinical treatments for peripheral nerve injury.Approval for animal use in this study was obtained from the Animal Ethics Committee of the Chinese PLA General Hospital on September 7,2016(approval No.2016-x9-07).展开更多
Cotton(Gossypium hirsutum)is an important fiber crop worldwide.Insect attack causes cotton yield and quality losses.However,little is known about the mechanism of cotton response to insect attack.We simulated insect f...Cotton(Gossypium hirsutum)is an important fiber crop worldwide.Insect attack causes cotton yield and quality losses.However,little is known about the mechanism of cotton response to insect attack.We simulated insect feeding by applying insect oral secretions(OS)to wounds,and combined transcriptome and metabolome analysis to investigate how OS from two major pest species(Helicoverpa armigera and Spodoptera litura)affect cotton defense responses.We found that respectively 12,668 and 13,379 genes were differentially expressed in comparison with wounding alone.On addition of OS,the jasmonic acid signaling pathway was rapidly and strongly induced,whereas genes involved in salicylic acid biosynthesis were downregulated.On constructing a coexpression gene network,we identified a hub gene encoding a leucine-rich repeat receptor kinase that may play an important role in early signal recognition and transduction.OS from the two insect species altered the abundance of flavonoid-related compounds in different patterns.Gossypol remained in lower concentration after OS application than after wounding alone,suggesting a suppressive effect of OS on cotton defense response.This study illustrated transcriptional and metabolic changes of cotton in responding to OS from two chewing insect species,identified potential key response genes,and revealed evidence for OS inhibition of wounding-induced cotton defense response.展开更多
基金the support of the National Natural Science Foundation of China(Nos.U22B2059,62176079)National Natural Science Foundation of Heilongjiang Province,China(No.YQ 2022F005)the Industry-University-Research Innovation Foundation of China University(No.2021ITA05009).
文摘With the emergence of pre-trained models,current neural networks are able to give task performance that is comparable to humans.However,we know little about the fundamental working mechanism of pre-trained models in which we do not know how they approach such performance and how the task is solved by the model.For example,given a task,human learns from easy to hard,whereas the model learns randomly.Undeniably,difficulty-insensitive learning leads to great success in natural language processing(NLP),but little attention has been paid to the effect of text difficulty in NLP.We propose a human learning matching index(HLM Index)to investigate the effect of text difficulty.Experiment results show:1)LSTM gives more human-like learning behavior than BERT.Additionally,UID-SuperLinear gives the best evaluation of text difficulty among four text difficulty criteria.Among nine tasks,some tasks’performance is related to text difficulty,whereas others are not.2)Model trained on easy data performs best in both easy and medium test data,whereas trained on hard data only performs well on hard test data.3)Train the model from easy to hard,leading to quicker convergence.
基金supported by the National Natural Science Foundation of China,No.31771052(to YW)the National Key Research&Development Program of China,No.2017YFA0104701,2017YFA0104702 and 2016YFC1101601+2 种基金the National Basic Research Program of China(973 Program),No.2014CB542201(to JP)the Natural Science Foundation of Beijing,No.7172202(to YW)the PLA Youth Training Project for Medical Science,No.16QNP144(to YW)
文摘Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory (Ml) and anti-inflammatory (M2) actions, and M2 macrophages have four subtypes. The co-action of Ml and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.
基金supported by the National Key R&D Program of China,No.2017YFA0104701(to YW)the National Natural Science Foundation of China,No.31771052(to YW)+1 种基金the Natural Science Foundation of Beijing of China,No.7172202(to YW)the PLA Youth Training Project for Medical Science of China,No.16QNP144(to YW)
文摘In recent years, the use of Schwann cell transplantation to repair peripheral nerve injury has attracted much attention. Animal-based studies show that the transplantation of Schwann cells in combination with nerve scaffolds promotes the repair of injured peripheral nerves. Autologous Schwann cell transplantation in humans has been reported recently. This article reviews current methods for removing the extracellular matrix and analyzes its composition and function. The development and secretory products of Schwann cells are also reviewed. The methods for the repair of peripheral nerve injuries that use myelin and Schwann cell transplantation are assessed. This survey of the literature data shows that using a decellularized nerve conduit combined with Schwann cells represents an effective strategy for the treatment of peripheral nerve injury. This analysis provides a comprehensive basis on which to make clinical decisions for the repair of peripheral nerve injury.
基金supported by the National Key Research&Development Program of China,No.2017YFA0104702(to AJS)the National Basic Research Program of China(973 Program),No.2014CB542201(to JP)
文摘A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors for regenerative success.Therefore,it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury.However,the identities of specific cytokines at various time points after sciatic nerve injury have not been determined.The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze,by protein microarray,the expression of different cytokines in the distal nerve after injury.Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines,e.g.,ciliary neurotrophic factor,were downregulated.The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines.Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways,Janus kinase/signal transducers and activators of transcription,phosphoinositide 3-kinase/protein kinase B,and notch signaling pathway.The cytokines involved in inflammation,immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes,cell-cell adhesion,and cell proliferation were up-regulated at 28 days after injury.Western blot analysis showed that the expression and changes of hepatocyte growth factor,glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis.The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration,as well as a basis for potential treatments of peripheral nerve injury.The study was approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital,China(approval number:2016-x9-07)in September 2016.
基金supported by National Key Research&Development Program of China,No.2016YFC11011601,2017YFA0104701the Youth Cultivation Project of Military Medical Science,China,No.15QNP091(to YW)People’s Liberation Army Youth Training Project for Medical Science of China,No.16QNP144(to YW)
文摘Sensory and motor nerve fibers of peripheral nerves have different anatomies and regeneration functions after injury. To gain a clear understanding of the biological processes behind these differences, we used a labeling technique termed isobaric tags for relative and absolute quantitation to investigate the protein profiles of spinal nerve tissues from Sprague-Dawley rats. In response to Wallerian degeneration, a total of 626 proteins were screened in sensory nerves, of which 368 were upregulated and 258 were downregulated. In addition, 637 proteins were screened in motor nerves, of which 372 were upregulated and 265 were downregulated. All identified proteins were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of bioinformatics, and the presence of several key proteins closely related to Wallerian degeneration were tested and verified using quantitative real-time polymerase chain reaction analyses. The differentially expressed proteins only identified in the sensory nerves were mainly relevant to various biological processes that included cell-cell adhesion, carbohydrate metabolic processes and cell adhesion, whereas differentially expressed proteins only identified in the motor nerves were mainly relevant to biological processes associated with the glycolytic process, cell redox homeostasis, and protein folding. In the aspect of the cellular component, the differentially expressed proteins in the sensory and motor nerves were commonly related to extracellular exosomes, the myelin sheath, and focal adhesion. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways. In conclusion, the present study screened differentially expressed proteins to reveal more about the differences and similarities between sensory and motor nerves during Wallerian degeneration. The present findings could provide a reference point for a future investigation into the differences between sensory and motor nerves in Wallerian degeneration and the characteristics of peripheral nerve regeneration. The study was approved by the Ethics Committee of the Chinese PLA General Hospital, China(approval No. 2016-x9-07) in September 2016.
基金supported financially by grants from the National Natural Science Foundation of China(Nos.31770389,81703393).
文摘Two new C21 steroidal glycosides,paniculatumosides H and I,together with four known ones were isolated from the roots of Cynanchum paniculatum(Bge.)Kitag.Their structures were identifed by spectroscopic methods including extensive 1D and 2D NMR techniques.All compounds were subjected to detect the anti-tobacco mosaic virus(TMV)activities and their cytotoxities against three human tumor cell lines(SMMC-7721,MDA-MB-231 and A549).The results showed that compounds 1 and 5 exhibited potent protective activities against TMV,while 2,4 and 6 had moderate efects on the SMMC7721 cancer cells viability.
基金supported financially by grants from the National Science Foundation of China(21432010,81573323,and 31770392)Technological Leading Talent Project of Yunnan Province(2015HA020)Central Asian Drug Discovery and Development Center of Chinese Academy of Sciences(CAM201402,CAM201302).
文摘A new ent-abietane diterpernoid,named ebracteolata D(1),along with 11 known analogues,was isolated from the roots of Euphorbia ebracteolata Hayata.The structure of 1 was elucidated on the basis of spectroscopic analysis and molecular modeling.Cytotoxicity of compounds 1-12 was evaluated as well as the effect on the NF-κB pathway.Among them,compound 12,jolkinolide B,displayed broad inhibitory effects against proliferation of tumor cell lines.Mechanistic studies indicated that the compound 12 can inhibit TNF-αinduced NF-κB activation,thereby inducing tumor cell apoptosis.
基金This study was supported by the National Natural Science Foundation of China,No.31771052(to YW)the National Key R&D Program of China,No.2017YFA0104702(to AJS)the Youth Cultivation Project of Military Medical Science,No.16QNP144(to YW).
文摘In our previous study,we investigated the dynamic expression of cytokines in the distal nerve stumps after peripheral nerve injury using microarray analysis,which can characterize the dynamic expression of proteins.In the present study,we used a rat model of right sciatic nerve transection to examine changes in the expression of cytokines at 1,7,14 and 28 days after injury using protein microarray analysis.Interleukins were increased in the distal nerve stumps at 1–14 days post nerve transection.However,growth factors and growth factor-related proteins were mainly upregulated in the proximal nerve stumps.The P-values of the inflammatory response,apoptotic response and cell-cell adhesion in the distal stumps were higher than those in the proximal nerve stumps,but the opposite was observed for angiogenesis.The number of cytokines related to axons in the distal stumps was greater than that in the proximal stumps,while the percentage of cytokines related to axons in the distal stumps was lower than that in the proximal nerve stumps.Visualization of the results revealed the specific expression patterns and differences in cytokines in and between the proximal and distal nerve stumps.Our findings offer potential therapeutic targets and should help advance the development of clinical treatments for peripheral nerve injury.Approval for animal use in this study was obtained from the Animal Ethics Committee of the Chinese PLA General Hospital on September 7,2016(approval No.2016-x9-07).
基金supported by the National Key Research and Development Program of China(2016YFD0100203-9)National R&D Project of Transgenic Crops(2016ZX08010001-006)National Natural Science Foundation of China(31371673)。
文摘Cotton(Gossypium hirsutum)is an important fiber crop worldwide.Insect attack causes cotton yield and quality losses.However,little is known about the mechanism of cotton response to insect attack.We simulated insect feeding by applying insect oral secretions(OS)to wounds,and combined transcriptome and metabolome analysis to investigate how OS from two major pest species(Helicoverpa armigera and Spodoptera litura)affect cotton defense responses.We found that respectively 12,668 and 13,379 genes were differentially expressed in comparison with wounding alone.On addition of OS,the jasmonic acid signaling pathway was rapidly and strongly induced,whereas genes involved in salicylic acid biosynthesis were downregulated.On constructing a coexpression gene network,we identified a hub gene encoding a leucine-rich repeat receptor kinase that may play an important role in early signal recognition and transduction.OS from the two insect species altered the abundance of flavonoid-related compounds in different patterns.Gossypol remained in lower concentration after OS application than after wounding alone,suggesting a suppressive effect of OS on cotton defense response.This study illustrated transcriptional and metabolic changes of cotton in responding to OS from two chewing insect species,identified potential key response genes,and revealed evidence for OS inhibition of wounding-induced cotton defense response.
