Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxid...Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.展开更多
Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.展开更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiqu...Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.展开更多
This editorial explores the transformative potential of artificial intelligence(AI)in identifying conflicts of interest(COIs)within academic and scientific research.By harnessing advanced data analysis,pattern recogni...This editorial explores the transformative potential of artificial intelligence(AI)in identifying conflicts of interest(COIs)within academic and scientific research.By harnessing advanced data analysis,pattern recognition,and natural language processing techniques,AI offers innovative solutions for enhancing transparency and integrity in research.This editorial discusses how AI can automatically detect COIs,integrate data from various sources,and streamline reporting processes,thereby maintaining the credibility of scientific findings.展开更多
Stephen Crane is one of the greatest figures in the history of American literature and his novella The Open Boat is widely known by people all over the world as a representative work of Naturalism. This paper aims at ...Stephen Crane is one of the greatest figures in the history of American literature and his novella The Open Boat is widely known by people all over the world as a representative work of Naturalism. This paper aims at exploring Naturalism in Stephen Crane's The Open Boat,which will guide the readers to understand American Naturalism accurately and thoroughly. It firstly introduces the author and his novel The Open Boat. Secondly,it progressively dissects Naturalism. It not only analyses the general characteristics of Naturalism with details in The Open Boat,but also interprets the distinguishing features of American Naturalism so that readers can better understand the features of American Naturalism. Through textual perusal,it further studies the unique characteristics of Stephen Crane's Naturalism and lays particular emphasis on Crane's special concern on the awakening of humanity. It is hoped that this thesis can help readers get an in-depth comprehension of Naturalism and gain some inspiration from TheOpenBoat.展开更多
Desire Under the Elms was a drama written by Eugene O'Neill in 1924,which is called the first greatest drama in American history.Through analyzing the naturalistic features in this drama and the combination of nat...Desire Under the Elms was a drama written by Eugene O'Neill in 1924,which is called the first greatest drama in American history.Through analyzing the naturalistic features in this drama and the combination of naturalism and realism reflected in Desire Under the Elms,this article aims to help readers understand the lines and the relevant connotations better.展开更多
William Faulkner is acclaimed as one of the most outstanding American writers of the twentieth century,enjoying a high reputation as a first-rate writer in American literature.Light in August is considered as a master...William Faulkner is acclaimed as one of the most outstanding American writers of the twentieth century,enjoying a high reputation as a first-rate writer in American literature.Light in August is considered as a masterpiece of Faulkner.With pro found moral significance,minute psychological descriptions and unique narrative techniques,William Faulkner passes his judg ments on the human life and the contradiction of human nature.展开更多
The short story"To build a Fire"by Jack London tells about the relationship between man and nature. Involving such themes as fear, death, and the individual versus nature,‘‘To Build a Fire''is a na...The short story"To build a Fire"by Jack London tells about the relationship between man and nature. Involving such themes as fear, death, and the individual versus nature,‘‘To Build a Fire''is a naturalistic work of fiction in which Jack London depicts human beings as subject to the laws of nature and controlled by their environment and their physical makeup.展开更多
Theodore Dreiser's Sister Carrie and Stephen Crane's The Open Boat are American naturalistic works in the 19 th centu-ry.The two novels reveal the writers' awareness of the American people's social sit...Theodore Dreiser's Sister Carrie and Stephen Crane's The Open Boat are American naturalistic works in the 19 th centu-ry.The two novels reveal the writers' awareness of the American people's social situation.This paper will analyze Sister Carrie andThe Open Boat from the point of naturalism.展开更多
Although E Maddy （1997） says on naturalism： ＂This is not, in itself, a philosophy of mathematics [...]＂ （161）, already by its name, or by those whose interest has called on it （Quine, Putnam et al.） ... it an...Although E Maddy （1997） says on naturalism： ＂This is not, in itself, a philosophy of mathematics [...]＂ （161）, already by its name, or by those whose interest has called on it （Quine, Putnam et al.） ... it anyhow reveals desire to be it. Insofar as otherwise, the semantic potential of the word leaves far behind it （after all scarce） results it achieved from the relation of an exact （mathematical） expression and （overly rich） intuitive reality of Being. We plead here already from the perspective of the slogan ＂One and All＂ of the first philosopher： Tales, when by the number （which one forebodes） one could go to such an extent into areas of reality （Pythagoras）, or when （especially in the human sphere） is being over again actual final cause of Aristotle the philosophy and the mathematics to accomplish far more fruitful encounter with the Being. Alain Badiou （1988） has already pointed that： ＂Mathematics is ontology,＂ and the category theory in mathematics, having covered by itself other fields of this science, continues to find applications in a series of＂non-traditional＂ domains of reality. In that correlation the philosophy can express its （primary） needs for truth, justice, beauty, ... as well as for the overall development in the sense of purpose--also because of an undreamed power of the technological development （of hardwares and softwares） today. Namely, the naturalism in mathematics, which developed an abundant reflection on the place （importance of） the mathematical idiom in sciences--in the balance of criticism--has come rather to meager provisions, such as： ＂preestablished harmony of thinking,＂ ＂ontic commitment,＂ （Quine 1960） ＂the hygiene of mind,＂ （Maddy 1996） ＂success argument,＂ （Putnam 1975） ＂pragmatic argument,＂ （Resnik 1981） etc., which only are few places from the encounter of an exact expression such as is mathematical one and the reality of natuural sciences. Instead of philosophy of mathematics to radicalize its claims from the perspective of that （powerful） mathematical idiom and the excessive reality of Being and man＇s place in it--this time, in the spirit of biocosmology （neo-Aristotelism）.展开更多
One of the most intriguing problems of philosophy and of mankind is the question whether humans have a free will. This question is heavily disputed between natural scientists and especially neuroscientists, who deny f...One of the most intriguing problems of philosophy and of mankind is the question whether humans have a free will. This question is heavily disputed between natural scientists and especially neuroscientists, who deny free will, and philosophers and other groups, who insist on free will. It is perplexing that both sides base their premise on the same precondition, namely naturalism. We will prove that naturalism automatically leads to physicalism, to materialism, and to reductionism. We will also prove here that it is logically not possible to have a free will if naturalism is true. Free will definitely requires an additional substance, a non-material soul, which cannot be part of our universe. This must not be in contradiction to our current knowledge of natural sciences.展开更多
Jack London is one of the most outstanding naturalistic writers in America who composed many renowned full-length novels.Jack London’s short story,"To Build a Fire"is a good reflection of naturalistic tende...Jack London is one of the most outstanding naturalistic writers in America who composed many renowned full-length novels.Jack London’s short story,"To Build a Fire"is a good reflection of naturalistic tendencies.It chooses"To Build a Fire"so as to fully understand his perspective of naturalism.First,it provides a brief introduction to Jack London and this short story.Second,it specifically displays naturalism in this short story from four aspects.Among them,objective authenticity is the most distinctive feature in naturalistic elements.Meanwhile,his literature creation is also deeply influenced by Darwin’s theory of evolution.It aims to investigate gold seeker’s failure that reflects natural selection and theory of survival of the fittest.Finally,it concludes that only by respecting nature can human beings survive in natural selection.Through the analysis of gold seeker’s tragic fate,it warns that the readers should master wild survival skills and live in harmony with nature.展开更多
基金supported by the National Natural Science Foundation of China,No.82071442 (to LS)a grant from the Jilin Provincial Department of Finance,No.JLSWSRCZX2021-004 (to LS)。
文摘Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.
文摘This editorial explores the transformative potential of artificial intelligence(AI)in identifying conflicts of interest(COIs)within academic and scientific research.By harnessing advanced data analysis,pattern recognition,and natural language processing techniques,AI offers innovative solutions for enhancing transparency and integrity in research.This editorial discusses how AI can automatically detect COIs,integrate data from various sources,and streamline reporting processes,thereby maintaining the credibility of scientific findings.
文摘Stephen Crane is one of the greatest figures in the history of American literature and his novella The Open Boat is widely known by people all over the world as a representative work of Naturalism. This paper aims at exploring Naturalism in Stephen Crane's The Open Boat,which will guide the readers to understand American Naturalism accurately and thoroughly. It firstly introduces the author and his novel The Open Boat. Secondly,it progressively dissects Naturalism. It not only analyses the general characteristics of Naturalism with details in The Open Boat,but also interprets the distinguishing features of American Naturalism so that readers can better understand the features of American Naturalism. Through textual perusal,it further studies the unique characteristics of Stephen Crane's Naturalism and lays particular emphasis on Crane's special concern on the awakening of humanity. It is hoped that this thesis can help readers get an in-depth comprehension of Naturalism and gain some inspiration from TheOpenBoat.
文摘Desire Under the Elms was a drama written by Eugene O'Neill in 1924,which is called the first greatest drama in American history.Through analyzing the naturalistic features in this drama and the combination of naturalism and realism reflected in Desire Under the Elms,this article aims to help readers understand the lines and the relevant connotations better.
文摘William Faulkner is acclaimed as one of the most outstanding American writers of the twentieth century,enjoying a high reputation as a first-rate writer in American literature.Light in August is considered as a masterpiece of Faulkner.With pro found moral significance,minute psychological descriptions and unique narrative techniques,William Faulkner passes his judg ments on the human life and the contradiction of human nature.
文摘The short story"To build a Fire"by Jack London tells about the relationship between man and nature. Involving such themes as fear, death, and the individual versus nature,‘‘To Build a Fire''is a naturalistic work of fiction in which Jack London depicts human beings as subject to the laws of nature and controlled by their environment and their physical makeup.
文摘Theodore Dreiser's Sister Carrie and Stephen Crane's The Open Boat are American naturalistic works in the 19 th centu-ry.The two novels reveal the writers' awareness of the American people's social situation.This paper will analyze Sister Carrie andThe Open Boat from the point of naturalism.
文摘Although E Maddy （1997） says on naturalism： ＂This is not, in itself, a philosophy of mathematics [...]＂ （161）, already by its name, or by those whose interest has called on it （Quine, Putnam et al.） ... it anyhow reveals desire to be it. Insofar as otherwise, the semantic potential of the word leaves far behind it （after all scarce） results it achieved from the relation of an exact （mathematical） expression and （overly rich） intuitive reality of Being. We plead here already from the perspective of the slogan ＂One and All＂ of the first philosopher： Tales, when by the number （which one forebodes） one could go to such an extent into areas of reality （Pythagoras）, or when （especially in the human sphere） is being over again actual final cause of Aristotle the philosophy and the mathematics to accomplish far more fruitful encounter with the Being. Alain Badiou （1988） has already pointed that： ＂Mathematics is ontology,＂ and the category theory in mathematics, having covered by itself other fields of this science, continues to find applications in a series of＂non-traditional＂ domains of reality. In that correlation the philosophy can express its （primary） needs for truth, justice, beauty, ... as well as for the overall development in the sense of purpose--also because of an undreamed power of the technological development （of hardwares and softwares） today. Namely, the naturalism in mathematics, which developed an abundant reflection on the place （importance of） the mathematical idiom in sciences--in the balance of criticism--has come rather to meager provisions, such as： ＂preestablished harmony of thinking,＂ ＂ontic commitment,＂ （Quine 1960） ＂the hygiene of mind,＂ （Maddy 1996） ＂success argument,＂ （Putnam 1975） ＂pragmatic argument,＂ （Resnik 1981） etc., which only are few places from the encounter of an exact expression such as is mathematical one and the reality of natuural sciences. Instead of philosophy of mathematics to radicalize its claims from the perspective of that （powerful） mathematical idiom and the excessive reality of Being and man＇s place in it--this time, in the spirit of biocosmology （neo-Aristotelism）.
文摘One of the most intriguing problems of philosophy and of mankind is the question whether humans have a free will. This question is heavily disputed between natural scientists and especially neuroscientists, who deny free will, and philosophers and other groups, who insist on free will. It is perplexing that both sides base their premise on the same precondition, namely naturalism. We will prove that naturalism automatically leads to physicalism, to materialism, and to reductionism. We will also prove here that it is logically not possible to have a free will if naturalism is true. Free will definitely requires an additional substance, a non-material soul, which cannot be part of our universe. This must not be in contradiction to our current knowledge of natural sciences.
文摘Jack London is one of the most outstanding naturalistic writers in America who composed many renowned full-length novels.Jack London’s short story,"To Build a Fire"is a good reflection of naturalistic tendencies.It chooses"To Build a Fire"so as to fully understand his perspective of naturalism.First,it provides a brief introduction to Jack London and this short story.Second,it specifically displays naturalism in this short story from four aspects.Among them,objective authenticity is the most distinctive feature in naturalistic elements.Meanwhile,his literature creation is also deeply influenced by Darwin’s theory of evolution.It aims to investigate gold seeker’s failure that reflects natural selection and theory of survival of the fittest.Finally,it concludes that only by respecting nature can human beings survive in natural selection.Through the analysis of gold seeker’s tragic fate,it warns that the readers should master wild survival skills and live in harmony with nature.
