The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiqui...The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.展开更多
In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,...In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.展开更多
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
Melamine sponge is a major concern for oil-water separation due to its lightweight,high porosity(>99%),cost-effectiveness,impressive mechanical properties,and chemical/thermal stability.However,its amphiphilic natu...Melamine sponge is a major concern for oil-water separation due to its lightweight,high porosity(>99%),cost-effectiveness,impressive mechanical properties,and chemical/thermal stability.However,its amphiphilic nature hinders selective oil absorption in water.Recent strategies to enhance hydrophobicity are reviewed,including synthetic methods and materials,with comprehensive explanations of the mechanisms driven by surface energy and roughness.Key performance indicators for MS in oil-water separation,including adsorption capacity,wettability,stability,emulsion separation,reversible wettability switching,flame retardancy,mechanical properties,and recyclability,are thoroughly discussed.In conclusion,this review provides insights into the future potential and direction of functional melamine sponges in oil-water separation.展开更多
Regulatory T(Treg)cells are pivotal for maintaining immune homeostasis and play essential roles in various diseases,such as autoimmune diseases,graft-versus-host disease(GVHD),tumors,and infectious diseases.Treg cells...Regulatory T(Treg)cells are pivotal for maintaining immune homeostasis and play essential roles in various diseases,such as autoimmune diseases,graft-versus-host disease(GVHD),tumors,and infectious diseases.Treg cells exert suppressive function via distinct mechanisms,including inhibitory cytokines,granzyme or perforin-mediated cytolysis,metabolic disruption,and suppression of dendritic cells.Forkhead Box P3(FOXP3),the characteristic transcription factor,is essential for Treg cell function and plasticity.Cumulative evidence has demonstrated that FOXP3 activity and Treg cell function are modulated by a variety of post-translational modifications(PTMs),including ubiquitination,acetylation,phosphorylation,methylation,glycosylation,poly(ADP-ribosyl)ation,and uncharacterized modifications.This review describes Treg cell suppressive mechanisms and summarizes the current evidence on PTM regulation of FOXP3 and Treg cell function.Understanding the regulatory role of PTMs in Treg cell plasticity and function will be helpful in designing therapeutic strategies for autoimmune diseases,GVHD,tumors,and infectious diseases.展开更多
Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesi...Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.展开更多
The NASICON-structured Na_(2)VTi(PO_(4))_(3)(NVTPO)has attracted significant attention due to its exceptional structural stability and rapid Na~+mobility.However,the development of this material has been hindered by p...The NASICON-structured Na_(2)VTi(PO_(4))_(3)(NVTPO)has attracted significant attention due to its exceptional structural stability and rapid Na~+mobility.However,the development of this material has been hindered by poor electronic conductivity and inadequate low-temperature performance.Herein,a feasible strategy of lattice regulation integrated with surface modification for NVTPO by nitrogen(N)deep doping is proposed.Systematic characterizations and theoretical calculations confirm that N is doped into both the inner crystal structure of NVTPO and the outer carbon layer.The blueshift of the P—O bonds and charge redistribution induced by the V/Ti—N bonds strengthen the local environment and narrow the bandgap,thereby enabling reversible structural evolution and improving electronic conductivity.As expected,the optimized NVTPO/N@CN material achieves an ultra-high capacity of 188.48 mA h g^(-1)at 10 mA g^(-1)and a long-term lifespan of 2000 cycles at 1 A g^(-1).More importantly,it exhibits competitive low-temperature performance(92.15%retention after 1000 cycles at 300 mA g^(-1)and-15℃)due to reduced charge transfer impedance and activation energy.This deep doping strategy modification is expected to broaden the applications of NASICON-type cathodes.展开更多
Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyl...Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
With the acceleration of advanced industrialization and urbanization,the environment is deteriorating rapidly,and non-renewable energy resources are depleted.The gradual advent of potential clean energy storage techno...With the acceleration of advanced industrialization and urbanization,the environment is deteriorating rapidly,and non-renewable energy resources are depleted.The gradual advent of potential clean energy storage technologies is particularly urgent.Electrochemical energy storage technologies have been widely used in multiple fields,especially supercapacitors and rechargeable batteries,as vital elements of storing renewable energy.In recent years,two-dimensional material MXene has shown great potential in energy and multiple application fields thanks to its excellent electrical properties,large specific surface area,and tunability.Based on the layered materials of MXene,researchers have successfully achieved the dual functions of energy storage and conversion by adjusting the surface terminals at the Fermi level.It is worth noting that compared with other two-dimensional materials,MXene has more active sites on the basal plane,showing excellent catalytic performance.In contrast,other two-dimensional materials have catalytic activity only at the edge sites.This article comprehensively overviews the synthesis process,structural characteristics,modification methods for MXene-based polymer materials,and their applications in electrochemical energy storage.It also briefly discusses the potential of MXene-polymer materials in electromagnetic shielding technology and sensors and looks forward to future research directions.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
Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttra...Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.展开更多
Fibrillization endows food proteins with anisotropic nanostructures,significantly enhancing their functional properties.The resultant food protein fibrils(FPFs)have garnered attention for their diverse applications ac...Fibrillization endows food proteins with anisotropic nanostructures,significantly enhancing their functional properties.The resultant food protein fibrils(FPFs)have garnered attention for their diverse applications across the food industry.However,the full potential of FPFs is hindered by inherent challenges,particularly their limited stability.This review critically examines the formation of FPFs in food processing,the new protein sources,and on the modification strategies of FPFs,thereby unlocking new avenues for FPF utilization in food processing.In particular,the strategies during and after fibrillization are highlighted.The first strategy is to modify the structure and function of protein fibrils by influencing fibrillization,such as through pretreatment,incubation conditions,nuclei induction,and ingredient interactions.The second strategy is to modify the mature FPFs by regulating their properties and interactions with other components.The review also discusses the potential applications and challenges of FPFs in food systems,such as food preservation,functional food design,and novel delivery carriers.展开更多
The startle response(SR)is a generalized defensive response elicited by the presentation of a sudden intense stimulus.The presentation of a less intense signal(prepulse)before the central stimulus(pulse)affects the am...The startle response(SR)is a generalized defensive response elicited by the presentation of a sudden intense stimulus.The presentation of a less intense signal(prepulse)before the central stimulus(pulse)affects the amplitude and latency of SR differently depending on the prepulse lead interval.The most studied form of such changes is prepulse inhibition(PPI),i.e.a decrease in SR amplitude at lead intervals of 50-500 ms.Prepulse facilitation,i.e.an increase in SR amplitude,can also be observed at lead intervals of 2000-4500 ms.The PPI deficiency has been found in a variety of psychopathologies and it has been suggested that it is a transdiagnostic phenomenon.However,some data from the literature support the existence of specific different nosologies,such as neurophysiological,neurochemical and molecular mechanisms that cause PPI lowering and affect prepulse facilitation of SR.This review provides a comparative analysis of studies on SR prepulse modification in healthy subjects and different groups of patients with mental or neurological disorders.The results of such an analysis may help to define directions for further research to improve methods of early diagnosis and to improve the validity of translational models.展开更多
Additive manufacturing(AM)has revolutionized the production of metal bone implants,enabling unprecedented levels of customization and functionality.Recent advancements in surface-modification technologies have been cr...Additive manufacturing(AM)has revolutionized the production of metal bone implants,enabling unprecedented levels of customization and functionality.Recent advancements in surface-modification technologies have been crucial in enhancing the performance and biocompatibility of implants.Through leveraging the versatility of AM techniques,particularly powder bed fusion,a range of metallic biomaterials,including stainless steel,titanium,and biodegradable alloys,can be utilized to fabricate implants tailored for craniofacial,trunk,and limb bone reconstructions.However,the potential of AM is contingent on addressing intrinsic defects that may hinder implant performance.Techniques such as sandblasting,chemical treatment,electropolishing,heat treatment,and laser technology effectively remove residual powder and improve the surface roughness of these implants.The development of functional coatings,applied via both dry and wet methods,represents a significant advancement in surface modification research.These coatings not only improve mechanical and biological interactions at the implant-bone interface but also facilitate controlled drug release and enhance antimicrobial properties.Addition-ally,micro-and nanoscale surface modifications using chemical and laser techniques can precisely sculpt implant surfaces to promote the desired cellular responses.This detailed exploration of surface engineering offers a wealth of opportunities for creating next-generation implants that are not only biocompatible but also bioactive,laying the foundation for more effective solutions in bone reconstruction.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
Objective:This study aimed to determine the effect of a culture-specificbehavior modificationprogram on glycated hemoglobin(HbA1c)and blood pressure among adults with diabetes and hypertension.Methods:This study was a...Objective:This study aimed to determine the effect of a culture-specificbehavior modificationprogram on glycated hemoglobin(HbA1c)and blood pressure among adults with diabetes and hypertension.Methods:This study was a single-blind randomized controlled trial design.From January to May 2024,a total of 60 patients with uncontrolled type 2 diabetes and hypertension from the primary care unit of a hospital in northeastern(Isan)Thailand were recruited.The intervention group received the usual care supplemented by a culture-specificbehavior modificationprogramm implemented through interactive classes and online web application consisting of information,motivation,and behavioral skills(diet,exercise,and medication use),the control group received the usual care.HbA1c and blood pressure measurements were collected at both baseline and at 12 weeks.Results:A total of 51 patients completed the study,the intervention group(n=26)and control group(n=25),respectively.After 12 weeks,23.1%of patients in the intervention group could maintain their HbA1c<7.0%;those with poorly controlled HbA1c decreased from 7.7%at baseline to 3.8%at 12 weeks.After 12 weeks,69.2%of intervention group participants could maintain systolic blood pressure<130 mmHg and 53.8%could keep diastolic blood pressure<80 mmHg.Analysis revealed that HbA1c,systolic and diastolic blood pressure levels in the intervention group were lower than the control group after the intervention(P<0.05).There was a statistically significantdifference a linear combination of HbA1c and blood pressure(systolic and diastolic BP levels)between time and group(P<0.05).Conclusion:These results suggest that healthcare providers can incorporate elements of this program to manage blood glucose and blood pressure effectively.Future studies should consider a longitudinal design with a larger sample size and include outcomes of lipid levels to confirmlong-term motivation.展开更多
Paraphenylenediamine(PPDA)-grafted maleic anhydride(MAH)-modified graphene oxide(PGO)was synthesized through a dual modification process.Initially,MAH was employed to modify graphene oxide(GO)to enhance its reactive s...Paraphenylenediamine(PPDA)-grafted maleic anhydride(MAH)-modified graphene oxide(PGO)was synthesized through a dual modification process.Initially,MAH was employed to modify graphene oxide(GO)to enhance its reactive sites.Subsequently,PPDA was utilized for further modification of MAH-modified GO(MGO).Through a comprehensive analysis,the successful grafting of MAH and PPDA onto GO was confirmed.It was concurrently established that the optimal ratio of PPDA to MGO is 1:1.This approach yielded PGO characterized by outstanding dispersibility and barrier properties in epoxy resin(EP)coaings for Q235 steel.The corrosion resistance of EP coatings containing varying amounts of PGO was assessed using electrochemical workstation and salt spray testing.After immersing in a 3.5 wt.%NaCl solution for 300 h,the composite coating containing 0.1 wt.%PGO exhibited superior performance in terms of low-frequency impedance modulus,measuring at 1.1×10^(8)Ωcm^(2).The lowest corrosion current density was 2.32×10^(–10)A cm^(−2),and the self-corrosion voltage was−0.301 V.Additionally,polarization testing indicated that this coating also displayed the lowest corrosion rate,specifically 1.383×10^(–7)mm/a.展开更多
Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While sympto...Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.展开更多
Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differe...Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.展开更多
Biodegradable metals have garnered considerable interest owing to their capacity for self-degradation following the repair of damaged tissues.This review commences with their historical development and clarifies the e...Biodegradable metals have garnered considerable interest owing to their capacity for self-degradation following the repair of damaged tissues.This review commences with their historical development and clarifies the essential prerequisites for their successful clinical translation.Subsequently,a detailed review of magnesium-based materials is presented from five critical areas of alloying,fabrication techniques,purification,surface modification,and structural design,systematically addressing their progress in biodegradation rate retardation,mechanical reinforcement,and biocompatibility enhancement.Furthermore,recent breakthroughs in vivo animal experiments and clinical translation of magnesium alloys are summarized.Finally,this review concludes with a critical assessment of the achievements and challenges encountered in the clinical application of these materials,and proposes practical strategies to address current limitations and guide future research perspectives.展开更多
基金supported by grants from the Major Projects of Health Science Research Foundation for Middle-Aged and Young Scientist of Fujian Province,China,No.2022ZQNZD01010010the National Natural Science Foundation of China,No.82371390Fujian Province Scientific Foundation,No.2023J01725(all to XC).
文摘The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No.22103055(to JG)the Natural Science Foundation of Hebei Province,No.F2024110001(to HC)Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System,Nos.2024LODTS215(to NL),2024LODTS216(to XS).
文摘In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.
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(Nos.52372093 and 52102145)the Key R&D Program of Shaanxi Province(Nos.2023GXLH-045 and 2022SF-168)+4 种基金the Xi’an Programs for Science and Technology Plan(Nos.2020KJRC0090 and 21XJZZ0045)the Opening Project of Shanxi Key Laboratory of Advanced Manufacturing Technology(No.XJZZ202001)the Xi’an Municipal Bureau of Science and Technology(No.21XJZZ0054)the Open Foundation of Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry,Ministry of Education,Shaanxi University of Science and Technology(No.KFKT2021-01)the Shaanxi Collaborative Innovation Center of Industrial Auxiliary Chemistry and Technology,Shaanxi University of Science and Technology(No.KFKT2021-01).
文摘Melamine sponge is a major concern for oil-water separation due to its lightweight,high porosity(>99%),cost-effectiveness,impressive mechanical properties,and chemical/thermal stability.However,its amphiphilic nature hinders selective oil absorption in water.Recent strategies to enhance hydrophobicity are reviewed,including synthetic methods and materials,with comprehensive explanations of the mechanisms driven by surface energy and roughness.Key performance indicators for MS in oil-water separation,including adsorption capacity,wettability,stability,emulsion separation,reversible wettability switching,flame retardancy,mechanical properties,and recyclability,are thoroughly discussed.In conclusion,this review provides insights into the future potential and direction of functional melamine sponges in oil-water separation.
基金supported by grants from the National Key R&D Program of China(2022YFC2403000 and 2021YFC2400500)the National Natural Science Foundation of China(32200728 and 32170925)+3 种基金the Clinical Research Project of Shenzhen Medical Academy of Research and Translation(C2301008)Shenzhen Science and Technology Program(JCYJ20220531100406014,JCYJ2022081800807016,RCBS20221008093336088,KQTD20210811090115019)Guangdong Basic and Applied Basic Research Foundation(2021A1515110375)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20210601).
文摘Regulatory T(Treg)cells are pivotal for maintaining immune homeostasis and play essential roles in various diseases,such as autoimmune diseases,graft-versus-host disease(GVHD),tumors,and infectious diseases.Treg cells exert suppressive function via distinct mechanisms,including inhibitory cytokines,granzyme or perforin-mediated cytolysis,metabolic disruption,and suppression of dendritic cells.Forkhead Box P3(FOXP3),the characteristic transcription factor,is essential for Treg cell function and plasticity.Cumulative evidence has demonstrated that FOXP3 activity and Treg cell function are modulated by a variety of post-translational modifications(PTMs),including ubiquitination,acetylation,phosphorylation,methylation,glycosylation,poly(ADP-ribosyl)ation,and uncharacterized modifications.This review describes Treg cell suppressive mechanisms and summarizes the current evidence on PTM regulation of FOXP3 and Treg cell function.Understanding the regulatory role of PTMs in Treg cell plasticity and function will be helpful in designing therapeutic strategies for autoimmune diseases,GVHD,tumors,and infectious diseases.
基金funded by National Natural Science Foundation of China(No.12172092,82174488,and 82305416)Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function(No.21DZ2271800)+1 种基金Shanghai Municipal Science and Technology Commission(No.23YF1418300)Scientific Research Project on Traditional Chinese Medicine of Shanghai Municipal Health Commission—Youth Guidance Category(No.2022QN018).
文摘Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.
基金supported by the National Natural Science Foundation of China(22272205 and 22178094)the Hunan Provincial Nature Science Foundation of China(2022JJ30685,2023JJ20059 and 2024JJ5292)+2 种基金the Hunan Provincial Science and Technology Plan Projects of China(2022RC3050 and 2017TP1001)the financial support from the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Provincesupport from the Young Elite Scientists Sponsorship Program by CAST(YESS20220432)。
文摘The NASICON-structured Na_(2)VTi(PO_(4))_(3)(NVTPO)has attracted significant attention due to its exceptional structural stability and rapid Na~+mobility.However,the development of this material has been hindered by poor electronic conductivity and inadequate low-temperature performance.Herein,a feasible strategy of lattice regulation integrated with surface modification for NVTPO by nitrogen(N)deep doping is proposed.Systematic characterizations and theoretical calculations confirm that N is doped into both the inner crystal structure of NVTPO and the outer carbon layer.The blueshift of the P—O bonds and charge redistribution induced by the V/Ti—N bonds strengthen the local environment and narrow the bandgap,thereby enabling reversible structural evolution and improving electronic conductivity.As expected,the optimized NVTPO/N@CN material achieves an ultra-high capacity of 188.48 mA h g^(-1)at 10 mA g^(-1)and a long-term lifespan of 2000 cycles at 1 A g^(-1).More importantly,it exhibits competitive low-temperature performance(92.15%retention after 1000 cycles at 300 mA g^(-1)and-15℃)due to reduced charge transfer impedance and activation energy.This deep doping strategy modification is expected to broaden the applications of NASICON-type cathodes.
基金supported by the National Natural Science Foundation of China,Nos.82030071(to JH),82272495(to YC)Science and Technology Major Project of Changsha,No.kh2103008(to JH)Graduate Students’Independent Innovative Projects of Hunan Province,No.CX20230311(to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
基金supported by the Natural Science Basic Research Plan in the Shaanxi Province of China(No.2023-JC-ZD-25)Shaanxi Province(Qin ChuangYuan)“Scientist+Engineer”Team Building(No.2022KXJ-040)+1 种基金Shaanxi Provincial Department of Education Key Scientific Research Project(No.22JY024)Science and Technology Guidance Project Plan of China National Textile and Apparel Council(No.2022038,2023018).
文摘With the acceleration of advanced industrialization and urbanization,the environment is deteriorating rapidly,and non-renewable energy resources are depleted.The gradual advent of potential clean energy storage technologies is particularly urgent.Electrochemical energy storage technologies have been widely used in multiple fields,especially supercapacitors and rechargeable batteries,as vital elements of storing renewable energy.In recent years,two-dimensional material MXene has shown great potential in energy and multiple application fields thanks to its excellent electrical properties,large specific surface area,and tunability.Based on the layered materials of MXene,researchers have successfully achieved the dual functions of energy storage and conversion by adjusting the surface terminals at the Fermi level.It is worth noting that compared with other two-dimensional materials,MXene has more active sites on the basal plane,showing excellent catalytic performance.In contrast,other two-dimensional materials have catalytic activity only at the edge sites.This article comprehensively overviews the synthesis process,structural characteristics,modification methods for MXene-based polymer materials,and their applications in electrochemical energy storage.It also briefly discusses the potential of MXene-polymer materials in electromagnetic shielding technology and sensors and looks forward to future research directions.
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the National Natural Science Foundation of China(Nos.82373722,22077144)Hunan Provincial Natural Science Foundation of China(No.2023JJ30527)+2 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515040006)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Key Research and Development Program of Guangdong Province(No.2020B1111110003).
文摘Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.
基金supported by the Natural Science Foundation of Jiangxi Province(20232BAB205075,20224ACB205014).
文摘Fibrillization endows food proteins with anisotropic nanostructures,significantly enhancing their functional properties.The resultant food protein fibrils(FPFs)have garnered attention for their diverse applications across the food industry.However,the full potential of FPFs is hindered by inherent challenges,particularly their limited stability.This review critically examines the formation of FPFs in food processing,the new protein sources,and on the modification strategies of FPFs,thereby unlocking new avenues for FPF utilization in food processing.In particular,the strategies during and after fibrillization are highlighted.The first strategy is to modify the structure and function of protein fibrils by influencing fibrillization,such as through pretreatment,incubation conditions,nuclei induction,and ingredient interactions.The second strategy is to modify the mature FPFs by regulating their properties and interactions with other components.The review also discusses the potential applications and challenges of FPFs in food systems,such as food preservation,functional food design,and novel delivery carriers.
文摘The startle response(SR)is a generalized defensive response elicited by the presentation of a sudden intense stimulus.The presentation of a less intense signal(prepulse)before the central stimulus(pulse)affects the amplitude and latency of SR differently depending on the prepulse lead interval.The most studied form of such changes is prepulse inhibition(PPI),i.e.a decrease in SR amplitude at lead intervals of 50-500 ms.Prepulse facilitation,i.e.an increase in SR amplitude,can also be observed at lead intervals of 2000-4500 ms.The PPI deficiency has been found in a variety of psychopathologies and it has been suggested that it is a transdiagnostic phenomenon.However,some data from the literature support the existence of specific different nosologies,such as neurophysiological,neurochemical and molecular mechanisms that cause PPI lowering and affect prepulse facilitation of SR.This review provides a comparative analysis of studies on SR prepulse modification in healthy subjects and different groups of patients with mental or neurological disorders.The results of such an analysis may help to define directions for further research to improve methods of early diagnosis and to improve the validity of translational models.
基金supported by National Natural Science Foundation of China(Grant No.52275343)Natural Science Foundation of Zhejiang Province(Grant No.LY23E050003)Ningbo Youth Science and Technology Innovation Leading Talent Project(Grant No.2023QL021).
文摘Additive manufacturing(AM)has revolutionized the production of metal bone implants,enabling unprecedented levels of customization and functionality.Recent advancements in surface-modification technologies have been crucial in enhancing the performance and biocompatibility of implants.Through leveraging the versatility of AM techniques,particularly powder bed fusion,a range of metallic biomaterials,including stainless steel,titanium,and biodegradable alloys,can be utilized to fabricate implants tailored for craniofacial,trunk,and limb bone reconstructions.However,the potential of AM is contingent on addressing intrinsic defects that may hinder implant performance.Techniques such as sandblasting,chemical treatment,electropolishing,heat treatment,and laser technology effectively remove residual powder and improve the surface roughness of these implants.The development of functional coatings,applied via both dry and wet methods,represents a significant advancement in surface modification research.These coatings not only improve mechanical and biological interactions at the implant-bone interface but also facilitate controlled drug release and enhance antimicrobial properties.Addition-ally,micro-and nanoscale surface modifications using chemical and laser techniques can precisely sculpt implant surfaces to promote the desired cellular responses.This detailed exploration of surface engineering offers a wealth of opportunities for creating next-generation implants that are not only biocompatible but also bioactive,laying the foundation for more effective solutions in bone reconstruction.
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 the 90th Anniversary of Chulalong-korn University Scholarship(Ratchadaphiseksomphot Endowment Fund)。
文摘Objective:This study aimed to determine the effect of a culture-specificbehavior modificationprogram on glycated hemoglobin(HbA1c)and blood pressure among adults with diabetes and hypertension.Methods:This study was a single-blind randomized controlled trial design.From January to May 2024,a total of 60 patients with uncontrolled type 2 diabetes and hypertension from the primary care unit of a hospital in northeastern(Isan)Thailand were recruited.The intervention group received the usual care supplemented by a culture-specificbehavior modificationprogramm implemented through interactive classes and online web application consisting of information,motivation,and behavioral skills(diet,exercise,and medication use),the control group received the usual care.HbA1c and blood pressure measurements were collected at both baseline and at 12 weeks.Results:A total of 51 patients completed the study,the intervention group(n=26)and control group(n=25),respectively.After 12 weeks,23.1%of patients in the intervention group could maintain their HbA1c<7.0%;those with poorly controlled HbA1c decreased from 7.7%at baseline to 3.8%at 12 weeks.After 12 weeks,69.2%of intervention group participants could maintain systolic blood pressure<130 mmHg and 53.8%could keep diastolic blood pressure<80 mmHg.Analysis revealed that HbA1c,systolic and diastolic blood pressure levels in the intervention group were lower than the control group after the intervention(P<0.05).There was a statistically significantdifference a linear combination of HbA1c and blood pressure(systolic and diastolic BP levels)between time and group(P<0.05).Conclusion:These results suggest that healthcare providers can incorporate elements of this program to manage blood glucose and blood pressure effectively.Future studies should consider a longitudinal design with a larger sample size and include outcomes of lipid levels to confirmlong-term motivation.
基金supports for this work are the Inner Mongolia Major Science and Technology Project(No.2020ZD0024)Natural Science Foundation of Inner Mongolia(No.2024LHMS05046)+5 种基金Local Science and Technology Development Project of the Central Government(Nos.2021ZY0006 and 2022ZY0011)2023 Inner Mongolia Autonomous Region Doctoral Research Innovation Project(No.B20231023Z)Inner Mongolia Autonomous Region key Research and Technological Achievements Transformation Plan Project(No.2023YFHH0063)Autonomous Region higher education Carbon peak carbon neutral research project(No.STZX202206)Basic Scientific Research Expenses Program of Universities directly under Inner Mongolia Autonomous Region(No.JY20220043)Graphite and Graphene New Materials Discipline Team of Inner Mongolia University of Technology(No.PY202066).
文摘Paraphenylenediamine(PPDA)-grafted maleic anhydride(MAH)-modified graphene oxide(PGO)was synthesized through a dual modification process.Initially,MAH was employed to modify graphene oxide(GO)to enhance its reactive sites.Subsequently,PPDA was utilized for further modification of MAH-modified GO(MGO).Through a comprehensive analysis,the successful grafting of MAH and PPDA onto GO was confirmed.It was concurrently established that the optimal ratio of PPDA to MGO is 1:1.This approach yielded PGO characterized by outstanding dispersibility and barrier properties in epoxy resin(EP)coaings for Q235 steel.The corrosion resistance of EP coatings containing varying amounts of PGO was assessed using electrochemical workstation and salt spray testing.After immersing in a 3.5 wt.%NaCl solution for 300 h,the composite coating containing 0.1 wt.%PGO exhibited superior performance in terms of low-frequency impedance modulus,measuring at 1.1×10^(8)Ωcm^(2).The lowest corrosion current density was 2.32×10^(–10)A cm^(−2),and the self-corrosion voltage was−0.301 V.Additionally,polarization testing indicated that this coating also displayed the lowest corrosion rate,specifically 1.383×10^(–7)mm/a.
文摘Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.
基金supported by the National Natural Science Foundation of China,(Nos.82272151,82204318)Liaoning Revitalization Talents Program(No.XLYC2203083)+2 种基金Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220389)Postdoctoral Fellowship Program of CPSF(No.GZC20231732)China Postdoctoral Science Foundation(Nos.2023TQ0222,2023MD744229).
文摘Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.
基金supported by the Science and Technology Planning Project of Guangdong Province(Nos.2024A0505040016 and 2023A0505050148)National Key Research and Development Project of China(2023YFB3809900/2023YFB3809902)Natural Science Foundation of Guangdong Province(No.2025A1515010026)。
文摘Biodegradable metals have garnered considerable interest owing to their capacity for self-degradation following the repair of damaged tissues.This review commences with their historical development and clarifies the essential prerequisites for their successful clinical translation.Subsequently,a detailed review of magnesium-based materials is presented from five critical areas of alloying,fabrication techniques,purification,surface modification,and structural design,systematically addressing their progress in biodegradation rate retardation,mechanical reinforcement,and biocompatibility enhancement.Furthermore,recent breakthroughs in vivo animal experiments and clinical translation of magnesium alloys are summarized.Finally,this review concludes with a critical assessment of the achievements and challenges encountered in the clinical application of these materials,and proposes practical strategies to address current limitations and guide future research perspectives.