Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein ...Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.展开更多
Cancer remains the leading cause of mortality worldwide.Radiotherapy(RT),a cornerstone of oncological treatment for over a century,has achieved great success in various cancers.However,radioresistance remains the prim...Cancer remains the leading cause of mortality worldwide.Radiotherapy(RT),a cornerstone of oncological treatment for over a century,has achieved great success in various cancers.However,radioresistance remains the primary factor leading to the failure of radiotherapy.Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure,either by loosening or tightening it.Here,we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal tissue cells.Furthermore,we discuss the regulatory mechanisms of histone modifications and the enzymes on the recruitment of proteins that recognize histone modifications.Consequently,these processes substantially affect the radiosensitivity of tumors.In addition to cancer cells,we highlight the intricate interplay between histone modification and radiosensitivity,both within and beyond the cancer cells.Meanwhile,various drugs targeting histone modifications emerge as a promising therapeutic strategy to overcome radioresistance of tumors as well as radioprotection.The combination of histone modification inhibitors with radiotherapy presents a novel approach to enhance cancer treatment outcomes in clinical practice.Nevertheless,the underlying mechanisms through which histone modifications influence cancer radiosensitivity require further elucidation to identify novel targets for radiotherapeutic intervention.展开更多
Infections associated with titanium(Ti)-based implants present significant challenges in clinical treatments,especially when biofilms already form on the implant surface.Many antimicrobial agents,including antibiotics...Infections associated with titanium(Ti)-based implants present significant challenges in clinical treatments,especially when biofilms already form on the implant surface.Many antimicrobial agents,including antibiotics,metallic nanoparticles and antimicrobial peptides,have been extensively used to deal with Ti implant infections.However,these chemical approaches suffer from potential toxicity,antibiotic resistance and poor long-term antibacterial performance.Hence,physical antibacterial surfaces on Ti-based implants have attracted increasing attention.The antibacterial behavior of different surfaces on Ti-based biomaterials against various bacteria only by physical properties of the implants themselves(e.g.,nanotopography)or exogenous physical stimulus(e.g.,photocatalysis)was reviewed,as well as parameters influencing the physical antibacterial processes,such as size,shape and density of the surface nanotextures,and bacterial growth phases.Besides,mechanisms of different fabrication techniques for the physical antibacterial surfaces on Ti-based biomaterials were also summarized.展开更多
Chronic kidney disease(CKD)has emerged as a formidable global health challenge,with a marked increase in its incidence,prevalence,and mortality rates.Renal fibrosis is a central pathophysiological process that drives ...Chronic kidney disease(CKD)has emerged as a formidable global health challenge,with a marked increase in its incidence,prevalence,and mortality rates.Renal fibrosis is a central pathophysiological process that drives the progression of CKD to end-stage renal disease.Despite its crucial role in CKD progression,effective clinical interventions to delay or mitigate renal fibrosis remain limited.A deeper understanding of the molecular mechanisms underlying renal fibrosis,along with the identification of potential drug targets and the development of novel therapeutics,holds immense research significance and clinical value for the prevention and treatment of CKD.In recent years,epigenetic research has garnered widespread attention and plays a pivotal role in various disease processes.Against this backdrop,the mechanisms by which epigenetic modifications exert their effects on renal fibrosis are gradually being elucidated,offering novel insights into the understanding of CKD.In this review,we summarize and analyze the intricate regulatory network of epigenetic modifications in renal fibrosis.We explore the promising antifibrotic effects demonstrated by various epigenetically modified drugs in fibrotic kidney models and discuss the challenges and opportunities in current research.These findings provide crucial insights for a deeper understanding of the molecular mechanisms underlying renal fibrosis and the development of novel therapeutic approaches.展开更多
Perfluorooctanoic acid(PFOA)is a highly bioaccumulative environmental endocrine disruptor and a persistent organic pollutant.Epigenetic modifications in DNA and RNA are crucial for regulating gene expression and are i...Perfluorooctanoic acid(PFOA)is a highly bioaccumulative environmental endocrine disruptor and a persistent organic pollutant.Epigenetic modifications in DNA and RNA are crucial for regulating gene expression and are involved in numerous physiological processes.However,research on the effects of PFOA on epigenetic modifications is still limited.In this study,we systematically investigated the alterations in epigenetic modifications in both DNA and RNA from the heart,liver,spleen,lung,kidney,and brain of C57BL/6N mice following exposure to PFOA at doses of 0,0.5,and 5 mg kg^(-1)d^(-1),utilizing liquid chromatography-tandem mass spectrometry(LC-MS/MS).The results indicated that exposure to PFOA inhibited weight gain in mice,and significant changes were observed in the organ coefficients of the liver,spleen,lungs,and heart in the high PFOA exposure group.Modifications in DNA and RNA exhibited tissue specificity.Orthogonal partial least squares discriminant analysis revealed that the control group and the high PFOA exposure group clustered well,suggesting that PFOA exposure significantly impacts epigenetic modifications in DNA and RNA.Specifically,PFOA exposure significantly affected the levels of 5-hydroxymethylcytosine(5hmC)in genomic DNA in the heart,lung,kidney,and liver tissues.For RNA modifications,significant changes were observed,with the levels of 12,13,10,6,12,and 14 modifications in the heart,liver,spleen,lung,kidney,and brain,respectively,altered in response to PFOA exposure.Our study highlights the significance of PFOA exposure in altering DNA and RNA modifications,providing a new perspective on understanding the toxicology of PFOA from an epigenetic standpoint.展开更多
Magnesium-based solid-state hydrogen storage materials(Mg-HSMs)exhibit significant potential for the global energy transition due to their large hydrogen capacity and energy density.However,their high operating temper...Magnesium-based solid-state hydrogen storage materials(Mg-HSMs)exhibit significant potential for the global energy transition due to their large hydrogen capacity and energy density.However,their high operating temperatures,low operating efficiencies,and short service life have severely hindered largescale applications.To address the above challenges,diverse modification strategies have been proposed.Catalytic modification,achieved by introducing catalysts to enable compositional compounding and structural refinement,enhances surface active site density and bulk hydrogen diffusion pathways,reduces hydrogen dissociation energy barriers,weakens Mg–H bonds,and significantly improves kinetic properties.This approach is considered one of the most effective strategies.However,as research advances,the structures,forms,and catalytic mechanisms of catalysts have become increasingly diverse.Despite progress,challenges such as fragmented research outcomes,inconsistent performance metrics,and an incomplete understanding of structure-property relationships remain unresolved.Therefore,this work systematically summarizes recent advances in catalytic modification strategies for Mg-HSMs,emphasizing the role of catalysts in enhancing reaction kinetics and structural stability,the diversity of catalyst types,forms,and the underlying mechanisms governing catalytic efficacy.Based on critical analysis,this work identifies the current key technical bottlenecks and proposes that the design of next-generation catalysts and the future development of Mg-HSMs should be guided by the principles of‘multiphase heterogeneous interfacial composites'and‘synergistic development',aiming to provide theoretical guidance for the optimization and advancement of their performance.展开更多
Pectin is a natural polysaccharide with a complex structure consisting of linear and branched regions rich in galacturonic acid.The growing interest in orange peel pectin can be attributed to its abundant supply.Accor...Pectin is a natural polysaccharide with a complex structure consisting of linear and branched regions rich in galacturonic acid.The growing interest in orange peel pectin can be attributed to its abundant supply.According to statistics,about 10 million tons of orange peel waste are produced worldwide each year.Traditionally,the extraction and utilization of pectin have focused on its gelling,thickening,and stabilizing properties in food.However,as more and more research teams have found that pectin has good biocompatibility,biodegradability and easy chemical modification,its potential in drug delivery systems,tissue engineering,and wound healing is gradually being explored.This review focuses on orange peel pectin polysaccharides and discusses its traditional and modern extraction techniques,especially the advanced method of subcritical water extraction.This study also outlines the structural modifications of pectin such as methylation and acetylation,and introduces its antioxidant and anticancer biological activities and their emerging roles in the development of advanced biomaterials such as bone tissue engineering and fibre pad dressings.展开更多
RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.Howe...RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.However,to the best of our knowledge,RNA modifications in peripheral white blood cells(immune cells)have not been systematically investigated before.Here we utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS)for the quantification of 19 chemical modifications in total RNA and 17 chemical modifications in small RNA in peripheral white blood cells from breast cancer patients and healthy controls.We found out 13 RNA modifications were up-regulated in total RNA samples of breast cancer patients.For small RNA samples,only N6-methyladenosine(m^(6)A)was down-regulated in breast cancer patients(P<0.0001).Receiver operating characteristic(ROC)curves analysis showed that N4-acetylcytidine(ac^(4)C)in total RNA had an area under curve(AUC)value of 0.833,and m^(6)A in small RNA had an AUC value of 0.994.Our results further illustrated that RNA modifications may play vital roles in immune cell biology of breast cancer,and may act as novel biomarkers for the diagnosis of breast cancer.展开更多
The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function a...The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.展开更多
The unit cell configuration of lattice structures critically influences their load-bearing and energy absorption performance.In this study,three novel lattice structures were developed by modifying the conventional FB...The unit cell configuration of lattice structures critically influences their load-bearing and energy absorption performance.In this study,three novel lattice structures were developed by modifying the conventional FBCCZ unit cell through reversing,combining,and turning strategies.The designed lattices were fabricated via laser powder bed fusion(LPBF)using Ti-6Al-4V powder,and the mechanical properties,energy absorption capacity,and deformation behaviors were systematically investigated through quasi-static compression tests and finite element simulations.The results demonstrate that the three modified lattices exhibit superior performance over the conventional FBCCZ structure in terms of fracture strain,specific yield strength,specific ultimate strength,specific energy absorption,and energy absorption efficiency,thereby validating the efficacy of unit cell modifications in enhancing lattice performance.Notably,the CFBCCZ and TFBCCZ lattices significantly outperform both the FBCCZ and RFBCCZ lattice structures in load-bearing and energy absorption.While TFBCCZ shows marginally higher specific elastic modulus and energy absorption efficiency than CFBCCZ,the latter achieves superior energy absorption due to its highest ultimate strength and densification strain.Finite element simulations further reveal that the modified lattices,through optimized redistribution and adjustment of internal nodes and struts,effectively alleviate stress concentration during loading.This structural modification enhances the structural integrity and deformation stability under external loads,enabling a synergistic enhancement of load-bearing capacity and energy absorption performance.展开更多
Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologie...Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.展开更多
During cellular proliferation DNA undergoes frequent rep-lication cycles in which errors inevitably accumulate.DNA simultaneously faces continuous damage from endogenous sources[e.g.,reactive oxygen species(ROS)]and e...During cellular proliferation DNA undergoes frequent rep-lication cycles in which errors inevitably accumulate.DNA simultaneously faces continuous damage from endogenous sources[e.g.,reactive oxygen species(ROS)]and environmen-tal stressors,such as ultraviolet(UV)and ionizing radiation(IR).Such lesions compromise genomic stability and may escalate into DNA double-strand breaks(DSBs).Failure to repair DSBs can ultimately trigger cell death1.展开更多
Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and pathologies.Histone modifications act as the key factors to modulate the chromatin accessibility.Different histo...Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and pathologies.Histone modifications act as the key factors to modulate the chromatin accessibility.Different histone modifications are strongly associated with the localization of chromatin.Heterochromatin primarily localizes at the nuclear periphery,where it interacts with lamina proteins to suppress gene expression.In this review,we summarize the potential bridges that have regulatory functions of histone modifications in chromatin organization and transcriptional regulation at the nuclear periphery.We use lamina-associated domains(LADs)as examples to elucidate the biological roles of the interactions between histone modifications and nuclear lamina in cell differentiation and development.In the end,we highlight the technologies that are currently used to identify and visualize histone modifications and LADs,which could provide spatiotemporal information for understanding their regulatory functions in gene expression and discovering new targets for diseases.展开更多
Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA...Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA methylation,histone modification,noncoding RNA regulation,and chromatin remodeling.Derived from the apical tissues of young permanent teeth,stem cells from apical papilla are odontogenic adult stem cells with high proliferation,self-renewal capacity,and differentiation potential.These cells play crucial roles in root formation and development.This article focuses on the two epigenetic regulatory mechanisms of histone modifications and non-coding RNA.This review summarizes,generalizes,and evaluates the status of research on the epigenetic regulation of the multidirectional differentiation of stem cells from the apical papilla,aiming to explore the mechanisms underlying the multidirectional differentiation process of these stem cells.展开更多
Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(P...Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.展开更多
The oral microenvironment plays a pivotal role in determining stem cell fate,driving both regeneration and pathological transformation.Emerging evidence suggests that post-translational modifications(PTMs)play a role ...The oral microenvironment plays a pivotal role in determining stem cell fate,driving both regeneration and pathological transformation.Emerging evidence suggests that post-translational modifications(PTMs)play a role as dynamic molecular signatures that regulate key signaling networks in dental-derived mesenchymal stem cells.These PTMs not only influence stem cell self-renewal and differentiation in periodontal tissue regeneration but also contribute to cancer stem cell plasticity and therapeutic resistance in oral squamous cell carcinoma(OSCC).At the pathway level,PTM programs interface with Wnt/β-catenin and bone morphogenetic protein/SMAD axis and integrate mitogen-activated protein kinase(p38/c-Jun N-terminal kinase)→runt-related transcription factor 2 in regeneration,whereas in OSCC/cancer stem cell they converge on Janus kinase/signal transducer and activator of transcription 3,phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin,and transforming growth factor-beta/SMAD-driven epithelial-mesenchymal transition.This review expounds on recent advances in PTM-mediated regulatory mechanisms in dentalderived mesenchymal stem cells,outlines their functional implications in inflammatory and tumor microenvironments,and discusses translational strategies-including localized,time-staged PTM modulation for regeneration and pathwayanchored combinations for OSCC-for regenerative medicine and targeted cancer therapies.Future research directions emphasize the integration of single-cell and spatial multi-omics with PTM profiling as a new approach to precision-based dental and oncological therapies.展开更多
基金supported by Applied Basic Research Joint Fund Project of Yunnan Province,No.202301AY070001-200Middle-aged Academic and Technical Training Project for High-Level Talents,No.202105AC160065+1 种基金Yunnan Clinical Medical Center for Neurological and Cardiovascular Diseases,No.YWLCYXZX2023300077Key Clinical Specialty of Neurology in Yunnan Province,No.300064(all to CL)。
文摘Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.
基金supported by the National Natural Science Foundation of China(82404200 and 82473574)Projects from Sichuan Province(2024ZYD0126,China)+1 种基金Key Innovation Project from Tibet Province(XZ202501ZY0131,China)Sichuan Science and Technology Program(MZGC20240002,China).
文摘Cancer remains the leading cause of mortality worldwide.Radiotherapy(RT),a cornerstone of oncological treatment for over a century,has achieved great success in various cancers.However,radioresistance remains the primary factor leading to the failure of radiotherapy.Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure,either by loosening or tightening it.Here,we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal tissue cells.Furthermore,we discuss the regulatory mechanisms of histone modifications and the enzymes on the recruitment of proteins that recognize histone modifications.Consequently,these processes substantially affect the radiosensitivity of tumors.In addition to cancer cells,we highlight the intricate interplay between histone modification and radiosensitivity,both within and beyond the cancer cells.Meanwhile,various drugs targeting histone modifications emerge as a promising therapeutic strategy to overcome radioresistance of tumors as well as radioprotection.The combination of histone modification inhibitors with radiotherapy presents a novel approach to enhance cancer treatment outcomes in clinical practice.Nevertheless,the underlying mechanisms through which histone modifications influence cancer radiosensitivity require further elucidation to identify novel targets for radiotherapeutic intervention.
基金National Natural Science Foundation of China(52171114)。
文摘Infections associated with titanium(Ti)-based implants present significant challenges in clinical treatments,especially when biofilms already form on the implant surface.Many antimicrobial agents,including antibiotics,metallic nanoparticles and antimicrobial peptides,have been extensively used to deal with Ti implant infections.However,these chemical approaches suffer from potential toxicity,antibiotic resistance and poor long-term antibacterial performance.Hence,physical antibacterial surfaces on Ti-based implants have attracted increasing attention.The antibacterial behavior of different surfaces on Ti-based biomaterials against various bacteria only by physical properties of the implants themselves(e.g.,nanotopography)or exogenous physical stimulus(e.g.,photocatalysis)was reviewed,as well as parameters influencing the physical antibacterial processes,such as size,shape and density of the surface nanotextures,and bacterial growth phases.Besides,mechanisms of different fabrication techniques for the physical antibacterial surfaces on Ti-based biomaterials were also summarized.
基金supported by the National Key R&D Program(2022YFC2502503,China)the National Natural Science Foundation of China(Nos.82270738 and 82400806)New Era Education Quality Improvement Project of Anhui Province(2024xscx053,China).
文摘Chronic kidney disease(CKD)has emerged as a formidable global health challenge,with a marked increase in its incidence,prevalence,and mortality rates.Renal fibrosis is a central pathophysiological process that drives the progression of CKD to end-stage renal disease.Despite its crucial role in CKD progression,effective clinical interventions to delay or mitigate renal fibrosis remain limited.A deeper understanding of the molecular mechanisms underlying renal fibrosis,along with the identification of potential drug targets and the development of novel therapeutics,holds immense research significance and clinical value for the prevention and treatment of CKD.In recent years,epigenetic research has garnered widespread attention and plays a pivotal role in various disease processes.Against this backdrop,the mechanisms by which epigenetic modifications exert their effects on renal fibrosis are gradually being elucidated,offering novel insights into the understanding of CKD.In this review,we summarize and analyze the intricate regulatory network of epigenetic modifications in renal fibrosis.We explore the promising antifibrotic effects demonstrated by various epigenetically modified drugs in fibrotic kidney models and discuss the challenges and opportunities in current research.These findings provide crucial insights for a deeper understanding of the molecular mechanisms underlying renal fibrosis and the development of novel therapeutic approaches.
基金supported by the National Key R&D Program of China(Nos.2022YFA0806600,2022YFC3400700)the Fundamental Research Funds for the Central Universities(No.2042024kf1045)+2 种基金the National Natural Science Foundation of China(No.22277093)the Key Research and Development Project of Hubei Province(No.2023BCB094)the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(No.JCRCGW-2022008)。
文摘Perfluorooctanoic acid(PFOA)is a highly bioaccumulative environmental endocrine disruptor and a persistent organic pollutant.Epigenetic modifications in DNA and RNA are crucial for regulating gene expression and are involved in numerous physiological processes.However,research on the effects of PFOA on epigenetic modifications is still limited.In this study,we systematically investigated the alterations in epigenetic modifications in both DNA and RNA from the heart,liver,spleen,lung,kidney,and brain of C57BL/6N mice following exposure to PFOA at doses of 0,0.5,and 5 mg kg^(-1)d^(-1),utilizing liquid chromatography-tandem mass spectrometry(LC-MS/MS).The results indicated that exposure to PFOA inhibited weight gain in mice,and significant changes were observed in the organ coefficients of the liver,spleen,lungs,and heart in the high PFOA exposure group.Modifications in DNA and RNA exhibited tissue specificity.Orthogonal partial least squares discriminant analysis revealed that the control group and the high PFOA exposure group clustered well,suggesting that PFOA exposure significantly impacts epigenetic modifications in DNA and RNA.Specifically,PFOA exposure significantly affected the levels of 5-hydroxymethylcytosine(5hmC)in genomic DNA in the heart,lung,kidney,and liver tissues.For RNA modifications,significant changes were observed,with the levels of 12,13,10,6,12,and 14 modifications in the heart,liver,spleen,lung,kidney,and brain,respectively,altered in response to PFOA exposure.Our study highlights the significance of PFOA exposure in altering DNA and RNA modifications,providing a new perspective on understanding the toxicology of PFOA from an epigenetic standpoint.
基金financially supported by the Key Research and Development Projects of Shaanxi Province(Grant Nos.2025CYYBXM-154 and 2024GX-YBXM-213)the Yulin Science and Technology Bureau(Grant Nos.2023-CXY-202 and 2024-CXY-154)+2 种基金the Scientific Research Program Funded by Shaanxi Provincial Education Department(Grant No.23JP008)the Natural Science Foundation of Qinghai Province for Distinguished Young Scholars(Grant No.2025-ZJ-966J)the Talent youth project of Chinese Academy of Sciences(Grant No.E410GC03)。
文摘Magnesium-based solid-state hydrogen storage materials(Mg-HSMs)exhibit significant potential for the global energy transition due to their large hydrogen capacity and energy density.However,their high operating temperatures,low operating efficiencies,and short service life have severely hindered largescale applications.To address the above challenges,diverse modification strategies have been proposed.Catalytic modification,achieved by introducing catalysts to enable compositional compounding and structural refinement,enhances surface active site density and bulk hydrogen diffusion pathways,reduces hydrogen dissociation energy barriers,weakens Mg–H bonds,and significantly improves kinetic properties.This approach is considered one of the most effective strategies.However,as research advances,the structures,forms,and catalytic mechanisms of catalysts have become increasingly diverse.Despite progress,challenges such as fragmented research outcomes,inconsistent performance metrics,and an incomplete understanding of structure-property relationships remain unresolved.Therefore,this work systematically summarizes recent advances in catalytic modification strategies for Mg-HSMs,emphasizing the role of catalysts in enhancing reaction kinetics and structural stability,the diversity of catalyst types,forms,and the underlying mechanisms governing catalytic efficacy.Based on critical analysis,this work identifies the current key technical bottlenecks and proposes that the design of next-generation catalysts and the future development of Mg-HSMs should be guided by the principles of‘multiphase heterogeneous interfacial composites'and‘synergistic development',aiming to provide theoretical guidance for the optimization and advancement of their performance.
文摘Pectin is a natural polysaccharide with a complex structure consisting of linear and branched regions rich in galacturonic acid.The growing interest in orange peel pectin can be attributed to its abundant supply.According to statistics,about 10 million tons of orange peel waste are produced worldwide each year.Traditionally,the extraction and utilization of pectin have focused on its gelling,thickening,and stabilizing properties in food.However,as more and more research teams have found that pectin has good biocompatibility,biodegradability and easy chemical modification,its potential in drug delivery systems,tissue engineering,and wound healing is gradually being explored.This review focuses on orange peel pectin polysaccharides and discusses its traditional and modern extraction techniques,especially the advanced method of subcritical water extraction.This study also outlines the structural modifications of pectin such as methylation and acetylation,and introduces its antioxidant and anticancer biological activities and their emerging roles in the development of advanced biomaterials such as bone tissue engineering and fibre pad dressings.
基金supported by National Natural Science Foundation of China(Nos.21927810,22336004 and 22176167).
文摘RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.However,to the best of our knowledge,RNA modifications in peripheral white blood cells(immune cells)have not been systematically investigated before.Here we utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS)for the quantification of 19 chemical modifications in total RNA and 17 chemical modifications in small RNA in peripheral white blood cells from breast cancer patients and healthy controls.We found out 13 RNA modifications were up-regulated in total RNA samples of breast cancer patients.For small RNA samples,only N6-methyladenosine(m^(6)A)was down-regulated in breast cancer patients(P<0.0001).Receiver operating characteristic(ROC)curves analysis showed that N4-acetylcytidine(ac^(4)C)in total RNA had an area under curve(AUC)value of 0.833,and m^(6)A in small RNA had an AUC value of 0.994.Our results further illustrated that RNA modifications may play vital roles in immune cell biology of breast cancer,and may act as novel biomarkers for the diagnosis of breast cancer.
文摘The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.
基金supported by National Key Lab of Aerospace Power System and Plasma Technology Foundation of China(Grant No.APSPT202301002)National Natural Science Foundation of China(Grant No.52001038)Natural Science Foundation of Chongqing,China(Grant Nos.cstc2019jcyj-msxm X0787 and cstc2021jcyj-msxm X0011)。
文摘The unit cell configuration of lattice structures critically influences their load-bearing and energy absorption performance.In this study,three novel lattice structures were developed by modifying the conventional FBCCZ unit cell through reversing,combining,and turning strategies.The designed lattices were fabricated via laser powder bed fusion(LPBF)using Ti-6Al-4V powder,and the mechanical properties,energy absorption capacity,and deformation behaviors were systematically investigated through quasi-static compression tests and finite element simulations.The results demonstrate that the three modified lattices exhibit superior performance over the conventional FBCCZ structure in terms of fracture strain,specific yield strength,specific ultimate strength,specific energy absorption,and energy absorption efficiency,thereby validating the efficacy of unit cell modifications in enhancing lattice performance.Notably,the CFBCCZ and TFBCCZ lattices significantly outperform both the FBCCZ and RFBCCZ lattice structures in load-bearing and energy absorption.While TFBCCZ shows marginally higher specific elastic modulus and energy absorption efficiency than CFBCCZ,the latter achieves superior energy absorption due to its highest ultimate strength and densification strain.Finite element simulations further reveal that the modified lattices,through optimized redistribution and adjustment of internal nodes and struts,effectively alleviate stress concentration during loading.This structural modification enhances the structural integrity and deformation stability under external loads,enabling a synergistic enhancement of load-bearing capacity and energy absorption performance.
基金supported by the National Natural Science Foundation of China(Nos.82271158,82301312,82071045,82101219,82071048).
文摘Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.
基金supported by grants fromthe Shenzhen Medical Research Fund(Grant No.A2302040).
文摘During cellular proliferation DNA undergoes frequent rep-lication cycles in which errors inevitably accumulate.DNA simultaneously faces continuous damage from endogenous sources[e.g.,reactive oxygen species(ROS)]and environmen-tal stressors,such as ultraviolet(UV)and ionizing radiation(IR).Such lesions compromise genomic stability and may escalate into DNA double-strand breaks(DSBs).Failure to repair DSBs can ultimately trigger cell death1.
基金financially supported by the National Natural Science Foundation of China(32100450 and 32471370 to Q.P.,12372302 to J.Q.)the Guangdong Pearl River Talent Program(2021QN02Y781 to Q.P.)the Evident&Shenzhen Bay Laboratory Joint Optical Microscopic Imaging Technology Development Program(S234602004-1 to Q.P.).
文摘Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and pathologies.Histone modifications act as the key factors to modulate the chromatin accessibility.Different histone modifications are strongly associated with the localization of chromatin.Heterochromatin primarily localizes at the nuclear periphery,where it interacts with lamina proteins to suppress gene expression.In this review,we summarize the potential bridges that have regulatory functions of histone modifications in chromatin organization and transcriptional regulation at the nuclear periphery.We use lamina-associated domains(LADs)as examples to elucidate the biological roles of the interactions between histone modifications and nuclear lamina in cell differentiation and development.In the end,we highlight the technologies that are currently used to identify and visualize histone modifications and LADs,which could provide spatiotemporal information for understanding their regulatory functions in gene expression and discovering new targets for diseases.
文摘Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA methylation,histone modification,noncoding RNA regulation,and chromatin remodeling.Derived from the apical tissues of young permanent teeth,stem cells from apical papilla are odontogenic adult stem cells with high proliferation,self-renewal capacity,and differentiation potential.These cells play crucial roles in root formation and development.This article focuses on the two epigenetic regulatory mechanisms of histone modifications and non-coding RNA.This review summarizes,generalizes,and evaluates the status of research on the epigenetic regulation of the multidirectional differentiation of stem cells from the apical papilla,aiming to explore the mechanisms underlying the multidirectional differentiation process of these stem cells.
文摘Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.
文摘The oral microenvironment plays a pivotal role in determining stem cell fate,driving both regeneration and pathological transformation.Emerging evidence suggests that post-translational modifications(PTMs)play a role as dynamic molecular signatures that regulate key signaling networks in dental-derived mesenchymal stem cells.These PTMs not only influence stem cell self-renewal and differentiation in periodontal tissue regeneration but also contribute to cancer stem cell plasticity and therapeutic resistance in oral squamous cell carcinoma(OSCC).At the pathway level,PTM programs interface with Wnt/β-catenin and bone morphogenetic protein/SMAD axis and integrate mitogen-activated protein kinase(p38/c-Jun N-terminal kinase)→runt-related transcription factor 2 in regeneration,whereas in OSCC/cancer stem cell they converge on Janus kinase/signal transducer and activator of transcription 3,phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin,and transforming growth factor-beta/SMAD-driven epithelial-mesenchymal transition.This review expounds on recent advances in PTM-mediated regulatory mechanisms in dentalderived mesenchymal stem cells,outlines their functional implications in inflammatory and tumor microenvironments,and discusses translational strategies-including localized,time-staged PTM modulation for regeneration and pathwayanchored combinations for OSCC-for regenerative medicine and targeted cancer therapies.Future research directions emphasize the integration of single-cell and spatial multi-omics with PTM profiling as a new approach to precision-based dental and oncological therapies.
