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
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
A scheme based on irregular V-shaped silicon nanoantennas is proposed to optimize transverse unidirectional scattering under plane wave irradiation.Traditional methods of designing regular shapes offer fewer parameter...A scheme based on irregular V-shaped silicon nanoantennas is proposed to optimize transverse unidirectional scattering under plane wave irradiation.Traditional methods of designing regular shapes offer fewer parameters and higher search efficiency.However,due to the limitations of regular shapes,it is challenging to meet high-precision design requirements.Irregular shape design allows for a broader range of adjustments,but the complexity of shape parameters leads to lower search efficiency and a higher likelihood of converging to local optima.展开更多
Real time prosody modification involves changing the prosody parameters such as pitch, duration and intensity of speech in real time without affecting the intelligibility and naturalness. In this paper prosody modific...Real time prosody modification involves changing the prosody parameters such as pitch, duration and intensity of speech in real time without affecting the intelligibility and naturalness. In this paper prosody modification is performed using instants of significant excitation (ISE) of the vocal tract system during production of speech. In the conventional prosody modification system the ISE are computed using group delay function, and it is computationally intensive task. In this paper, we propose computationally efficient methods to determine the ISE suitable for prosody modification in interactive (real time) applications. The overall computational time for the prosody modification by using the proposed method is compared with the conventional prosody modification method which uses the group delay function for computing the ISE.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
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
In this paper,the stability of the results of ultrasonic wood surface modification after long-term storage,including macroscopic properties and microstructure of specimens,was investigated.Specimens of aspen wood(Popu...In this paper,the stability of the results of ultrasonic wood surface modification after long-term storage,including macroscopic properties and microstructure of specimens,was investigated.Specimens of aspen wood(Populus tremula)were processed by the developed ultrasonic method of wood surface modification in three different treatment modes and the surface hardness of the specimens was evaluated after processing and after storing the specimens for more than 5 years since long-term stability is an important factor for the use of ultrasonically modified sawn timber as construction and finishing materials.The obtained results of surface hardness measurements by the Leeb method showed that the decrease in hardness after long-term storage is approximately 6.6%for the lowest degree of treatment and approximately 3.4%and 2.4%for medium and high degrees of treatment,taking into account the fact of the average increase in surface hardness approximately 2–4 times,this decrease is insignificant.The internal structure of the specimens after storage was studied by scanning electron microscope(SEM),and deformations of the wood surface layer without damage or rupture were analyzed.The derived stable results confirm the potential of the ultrasonic method for wood surface modification.展开更多
Rotary friction welding is a highly effective solid-state technique for joining dissimilar materials,which offers the potential for significant weight reduction without compromising strength.Traditionally,during rotar...Rotary friction welding is a highly effective solid-state technique for joining dissimilar materials,which offers the potential for significant weight reduction without compromising strength.Traditionally,during rotary friction welding,the severely deformed material,or flash,is expelled from the interface and machined away to achieve the desired joint geometry.However,this work introduces a novel approach:trapping the flash within the joint to improve joint properties.The study investigates two different interface geometry combinationsdflat-flat and flat-taper interfaces.Previous research shows that Ni interlayer between steel and titanium can enhance the joint strength.This study builds on the existing knowledge(effect of Ni interlayer)by examining the influence of interface geometry to further improve the dissimilar joint performance.The experimental results,including tensile testing and microstructural characterization,highlight the superior performance of the flat-taper interface.The modified geometry minimizes flash loss,providing a cavity that retains both the flash and the Ni interlayer within the joint.This retention promotes dynamic recrystallization,resulting in refined grain structures near the interface.Moreover,the trapped Ni interlayer effectively prevents the formation of brittle Fe-Ti intermetallic compounds at the dissimilar material interface.The findings reveal that the flat-taper interface improved joint strength by an impressive 105%compared to the flat-flat interface.This innovative geometry modification demonstrates the potential to enhance mechanical properties of dissimilar joints through better flash and interlayer management.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
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
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
Four types of submicron Ag-coated Cu particles with different Ag contents were prepared as sintering paste fillers,and the Ag contents of the particles were measured to be 10,20,30,and 40 wt.%.Four types of particles(...Four types of submicron Ag-coated Cu particles with different Ag contents were prepared as sintering paste fillers,and the Ag contents of the particles were measured to be 10,20,30,and 40 wt.%.Four types of particles(in order of increasing Ag content:A10,A20,A30,and A40)were surface-modified with stearic acid,to suppress the Ag shell dewetting and improve sinterability.The surface-modified particles were mixed with a polyol-based solvent to fabricate a resin-free paste.Subsequently,the pastes were screen-printed onto a slide glass and sintered at 250°C in a nitrogen atmosphere for 1-10 min to form an electrode.The electrical resistivity of the sintered film as a function of sintering time was measured using a four-point probe.All the four surface-modified Cu@Ag particles with different Ag contents exhibited decreased electrical resistivity.Particularly,the largest difference in values after and before the surface modification was observed for A40 with the highest Ag content;the electrical resistivities of the initial and surface-modified particles were 1.51×10^(-4) and 6.67×10^(-5)Ω·cm,respectively,after sintering for 10 min.The findings of this study confirmed that the surface modification using stearic acid effectively suppressed the dewetting of the Ag shell and improved the sinterability of the submicron Cu@Ag particles.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
Before-and-after methods have been effectively used in the road safety studies to estimate Crash Modification Factors (CMFs) of individual treatments as well as the multiple treatments on roadways. Since the common pr...Before-and-after methods have been effectively used in the road safety studies to estimate Crash Modification Factors (CMFs) of individual treatments as well as the multiple treatments on roadways. Since the common practice is to apply multiple treatments on road segments, it is important to have a method to estimate CMFs of individual treatment so that the effect of each treatment towards improving the road safety can be identified. Even though there are methods introduced by researchers to combine multiple CMFs or to isolate the safety effectiveness of individual treatment from CMFs developed for multiple treatments, those methods have to be tested before using them. This study considered two multiple treatments namely 1) Safety edge with lane widening 2) Adding 2 ft paved shoulders with shoulder rumble strips and/or asphalt resurfacing. The objectives of this research are to propose a regression-based method to estimate individual CMFs estimate CMFs using before-and-after Empirical Bayes method and compare the results. The results showed that having large sample size gives accurate predictions with smaller standard error and p-values of the considered treatments. Also, results obtained from regression method are similar to the EB method even though the values are not exactly the same. Finally, it was seen that the safety edge treatment reduces crashes by 15% - 25% and adding 2 ft shoulders with rumble strips reduces crashes by 25% - 49%.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
Viruses and their hosts have co-evolved for million years. In order to successfully replicate their genome, viruses need to usurp the biosynthetic machinery of the host cell. Depending on the complexity and the nature...Viruses and their hosts have co-evolved for million years. In order to successfully replicate their genome, viruses need to usurp the biosynthetic machinery of the host cell. Depending on the complexity and the nature of the genome, replication might involve or not a relatively large subset of viral products, in addition to a number of host cell factors, and take place in several subcellular compartments, including the nucleus,the cytoplasm, as well as virus-induced, rearranged membranes. Therefore viruses need to ensure the correct subcellular localization of their effectors and to be capable of disguising from the cellular defensive mechanisms. In addition, viruses are capable of exploiting host cell activities, by modulating their post-translational modification apparatus, resulting in profound modifications in the function of cellular and viral products. Not surprisingly infection of host cells by these parasites can lead to alterations of cellular differentiation and growing properties, with important pathogenic consequences. In the present hot topic highlight entitled "Reprogramming the host: modification of cell functions upon viral infection", a number of leading virologists and cell biologist thoroughly describe recent advances in our understanding of how viruses modulate cellular functions to achieve successful replication and propagation at the expenses of human cells.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 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supported by the National Natural Science Foundation of China(Nos.62475121 and 62335012)。
文摘A scheme based on irregular V-shaped silicon nanoantennas is proposed to optimize transverse unidirectional scattering under plane wave irradiation.Traditional methods of designing regular shapes offer fewer parameters and higher search efficiency.However,due to the limitations of regular shapes,it is challenging to meet high-precision design requirements.Irregular shape design allows for a broader range of adjustments,but the complexity of shape parameters leads to lower search efficiency and a higher likelihood of converging to local optima.
文摘Real time prosody modification involves changing the prosody parameters such as pitch, duration and intensity of speech in real time without affecting the intelligibility and naturalness. In this paper prosody modification is performed using instants of significant excitation (ISE) of the vocal tract system during production of speech. In the conventional prosody modification system the ISE are computed using group delay function, and it is computationally intensive task. In this paper, we propose computationally efficient methods to determine the ISE suitable for prosody modification in interactive (real time) applications. The overall computational time for the prosody modification by using the proposed method is compared with the conventional prosody modification method which uses the group delay function for computing the ISE.
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.
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.
文摘In this paper,the stability of the results of ultrasonic wood surface modification after long-term storage,including macroscopic properties and microstructure of specimens,was investigated.Specimens of aspen wood(Populus tremula)were processed by the developed ultrasonic method of wood surface modification in three different treatment modes and the surface hardness of the specimens was evaluated after processing and after storing the specimens for more than 5 years since long-term stability is an important factor for the use of ultrasonically modified sawn timber as construction and finishing materials.The obtained results of surface hardness measurements by the Leeb method showed that the decrease in hardness after long-term storage is approximately 6.6%for the lowest degree of treatment and approximately 3.4%and 2.4%for medium and high degrees of treatment,taking into account the fact of the average increase in surface hardness approximately 2–4 times,this decrease is insignificant.The internal structure of the specimens after storage was studied by scanning electron microscope(SEM),and deformations of the wood surface layer without damage or rupture were analyzed.The derived stable results confirm the potential of the ultrasonic method for wood surface modification.
文摘Rotary friction welding is a highly effective solid-state technique for joining dissimilar materials,which offers the potential for significant weight reduction without compromising strength.Traditionally,during rotary friction welding,the severely deformed material,or flash,is expelled from the interface and machined away to achieve the desired joint geometry.However,this work introduces a novel approach:trapping the flash within the joint to improve joint properties.The study investigates two different interface geometry combinationsdflat-flat and flat-taper interfaces.Previous research shows that Ni interlayer between steel and titanium can enhance the joint strength.This study builds on the existing knowledge(effect of Ni interlayer)by examining the influence of interface geometry to further improve the dissimilar joint performance.The experimental results,including tensile testing and microstructural characterization,highlight the superior performance of the flat-taper interface.The modified geometry minimizes flash loss,providing a cavity that retains both the flash and the Ni interlayer within the joint.This retention promotes dynamic recrystallization,resulting in refined grain structures near the interface.Moreover,the trapped Ni interlayer effectively prevents the formation of brittle Fe-Ti intermetallic compounds at the dissimilar material interface.The findings reveal that the flat-taper interface improved joint strength by an impressive 105%compared to the flat-flat interface.This innovative geometry modification demonstrates the potential to enhance mechanical properties of dissimilar joints through better flash and interlayer management.
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.
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 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.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2021R1A2C1007400)supported,partly,by the National R&D Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(Nos.NRF-2020M3H4A3106383,NRF2020M3H4A3081764)+1 种基金supported,partly,by ETRI(No.21YB1610)supported by a Korea Institute for Advancement of Technology(KIAT)grant funded by the Korea Government(MOTIE)(No.P0008458,HRD Program for Industrial Innovation)。
文摘Four types of submicron Ag-coated Cu particles with different Ag contents were prepared as sintering paste fillers,and the Ag contents of the particles were measured to be 10,20,30,and 40 wt.%.Four types of particles(in order of increasing Ag content:A10,A20,A30,and A40)were surface-modified with stearic acid,to suppress the Ag shell dewetting and improve sinterability.The surface-modified particles were mixed with a polyol-based solvent to fabricate a resin-free paste.Subsequently,the pastes were screen-printed onto a slide glass and sintered at 250°C in a nitrogen atmosphere for 1-10 min to form an electrode.The electrical resistivity of the sintered film as a function of sintering time was measured using a four-point probe.All the four surface-modified Cu@Ag particles with different Ag contents exhibited decreased electrical resistivity.Particularly,the largest difference in values after and before the surface modification was observed for A40 with the highest Ag content;the electrical resistivities of the initial and surface-modified particles were 1.51×10^(-4) and 6.67×10^(-5)Ω·cm,respectively,after sintering for 10 min.The findings of this study confirmed that the surface modification using stearic acid effectively suppressed the dewetting of the Ag shell and improved the sinterability of the submicron Cu@Ag particles.
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Before-and-after methods have been effectively used in the road safety studies to estimate Crash Modification Factors (CMFs) of individual treatments as well as the multiple treatments on roadways. Since the common practice is to apply multiple treatments on road segments, it is important to have a method to estimate CMFs of individual treatment so that the effect of each treatment towards improving the road safety can be identified. Even though there are methods introduced by researchers to combine multiple CMFs or to isolate the safety effectiveness of individual treatment from CMFs developed for multiple treatments, those methods have to be tested before using them. This study considered two multiple treatments namely 1) Safety edge with lane widening 2) Adding 2 ft paved shoulders with shoulder rumble strips and/or asphalt resurfacing. The objectives of this research are to propose a regression-based method to estimate individual CMFs estimate CMFs using before-and-after Empirical Bayes method and compare the results. The results showed that having large sample size gives accurate predictions with smaller standard error and p-values of the considered treatments. Also, results obtained from regression method are similar to the EB method even though the values are not exactly the same. Finally, it was seen that the safety edge treatment reduces crashes by 15% - 25% and adding 2 ft shoulders with rumble strips reduces crashes by 25% - 49%.
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.
文摘Viruses and their hosts have co-evolved for million years. In order to successfully replicate their genome, viruses need to usurp the biosynthetic machinery of the host cell. Depending on the complexity and the nature of the genome, replication might involve or not a relatively large subset of viral products, in addition to a number of host cell factors, and take place in several subcellular compartments, including the nucleus,the cytoplasm, as well as virus-induced, rearranged membranes. Therefore viruses need to ensure the correct subcellular localization of their effectors and to be capable of disguising from the cellular defensive mechanisms. In addition, viruses are capable of exploiting host cell activities, by modulating their post-translational modification apparatus, resulting in profound modifications in the function of cellular and viral products. Not surprisingly infection of host cells by these parasites can lead to alterations of cellular differentiation and growing properties, with important pathogenic consequences. In the present hot topic highlight entitled "Reprogramming the host: modification of cell functions upon viral infection", a number of leading virologists and cell biologist thoroughly describe recent advances in our understanding of how viruses modulate cellular functions to achieve successful replication and propagation at the expenses of human cells.