A key pathological feature of Parkinson’s disease(PD)is that lysosomes are overwhelmed with cellular materials that need to be degraded and cleared.While the build-up of protein is characteristic of neurodegenerative...A key pathological feature of Parkinson’s disease(PD)is that lysosomes are overwhelmed with cellular materials that need to be degraded and cleared.While the build-up of protein is characteristic of neurodegenerative diseases such as PD and Alzheimer’s disease(AD)and is thought to reflect lysosome dysfunction,lipid accumulation may also contribute to and be indicative of severe lysosomal dysfunction.Much is known about the detrimental effects of glucosylceramide accumulation in PD lysosomes.展开更多
Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules form...Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.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
Proline accumulation has been shown to occur in plants in response to various environmental stresses.Although proline metabolismrelated genes have been functionally characterized,the inter-organ transport of proline i...Proline accumulation has been shown to occur in plants in response to various environmental stresses.Although proline metabolismrelated genes have been functionally characterized,the inter-organ transport of proline in stressed plants remains unclear.In this study,free proline was detected with significant accumulations in the roots,stems,and leaves of watermelon drought-tolerant germplasm M08 and drought-susceptible line Y34 under drought stress.Expression profiling and enzyme activity measurements revealed that ClP5CS1 gene,rather than its paralog ClP5CS2,mainly contributes to the proline synthesis in leaves via the Glu pathway.Additionally,over-expression of the ClP5CS genes significantly enhanced the drought tolerance of transgenic Arabidopsis lines.Furthermore,we confirmed that proline is mainly synthesized in leaves and transported to roots in watermelon under drought stress.Transcriptome and expression analyses revealed that the genes involved in proline metabolism exhibited different expression levels.Specifically,ClP5CS1 was upregulated in leaves and roots,while ClP5CS2 was downregulated under drought stress.Also,415 and 362 differently expressed TFs were identified in roots and leaves,respectively,with the majority upregulated in the former.Ultimately,a model for proline metabolism was proposed.The findings of this study provided new insights into the biosynthesis,transport,and regulatory mechanism of drought-induced proline in plants.展开更多
Plasma spray-physical vapor deposition(PS-PVD)has exhibited the potential ability to prepare columnar structures for advanced thermal barrier coatings(TBCs).The coating structure is nominally affected by operating par...Plasma spray-physical vapor deposition(PS-PVD)has exhibited the potential ability to prepare columnar structures for advanced thermal barrier coatings(TBCs).The coating structure is nominally affected by operating parameters,but it is controlled by the type of deposition unit actually and essentially.In order to realize the columnar structure deposited by gaseous phase units,the transition behavior of gaseous phase units to clusters must be fundamentally understood.This work investigated the transport process of gaseous phase units in the PS-PVD near-substrate boundary layer along with the condensation behavior.The Monte Carlo method was used to examine the transport process and condensation behavior of gaseous phase units under different scale boundary layers.Simulation results show that it is easier to form more numerous larger clusters at the edge of the plasma jet than at the center.Based on the understanding of the changes in deposition unit caused by the condensation of gaseous phase in the near-substrate boundary layer of PS-PVD,an outlook towards TBCs with different structures is presented.And it is in good agreement with the experimental data.展开更多
We study the stabilization of the soliton transported bio-energy by the dynamic equations in the improved Davydov theory from four aspects containing the feature of free motion and states of the soliton at the long-ti...We study the stabilization of the soliton transported bio-energy by the dynamic equations in the improved Davydov theory from four aspects containing the feature of free motion and states of the soliton at the long-time motion and at biological temperature 300 K and behaviors of collision of the solitons by Runge–Kutta method and physical parameter values appropriate to the α-helix protein molecules. We prove that the new solitons can move without dispersion at a constant speed retaining its shape and energy in free and long-time motions and can go through each other without scattering. If considering further influence of the temperature effect of heat bath on the soliton, it is still thermally stable at biological temperature 300 K and in a time as long as 300 ps and amino acid spacings as large as 400, which shows that the lifetime of the new soliton is at least 300 ps, which is consistent with analytic result obtained by quantum perturbation theory. These results exhibit that the new soliton is a possible carrier of bio-energy transport and the improved model is possibly a candidate for the mechanism of this transport.展开更多
To demonstrate the distribution and expression of heat shock proteins (HSPs) in the liver, five kinds of HSPs, namely HSP70, HSP72, HSP86, HSP90 and HSP27 were determined after a long distance transport using immunohi...To demonstrate the distribution and expression of heat shock proteins (HSPs) in the liver, five kinds of HSPs, namely HSP70, HSP72, HSP86, HSP90 and HSP27 were determined after a long distance transport using immunohistochemistry and Western blot. All five HSPs were regularly detected in the liver of both the transported and the control group. Both nuclear and cytoplasmic labeling was present in hepatic cells; however, localization of HSPs was quite different in hepatocytes. The majority of HSP70, HSP72 and HSP27 appeared to predominate in cytoplasm of the hepatocytes. Nuclear signals of HSP90 and HSP86 were most prominent in hepatocytes in which immunostaining in the cytoplasm was relatively weak compared with that in the nucleus. There was subjectively lower staining in the edge of hepatic labule, and lower numbers of HSPs labeled hepatic cells corresponded to light microscopic lesions. The obvious inductions of some HSPs were detected in the liver, especially the HSP90(P<0.01) which belongs to the HSP90 family. However, the obvious reductions of HSP86(P<0.05), which belong to the HSP90 family, and HSP27 (P <0.05), which belong to small families, were detected in stressed pig liver after six hours of long distance transportation.展开更多
We study numerically the propagating properties of soliton-transported bio-energy excited in the a-helix protein molecules with three channels in the cases of the short-time and long-time motions and its features of c...We study numerically the propagating properties of soliton-transported bio-energy excited in the a-helix protein molecules with three channels in the cases of the short-time and long-time motions and its features of collision at temperature T = 0 and biological temperature T = 300 K by the dynamic equations in the improved Davydov theory and fourth-order Runge-Kutta method, respectively. From these simulation experiments we see that the new solitons in the improved model can move without dispersion at a constant speed retaining its shape and energy in the cases of motion of both short-time or T = 0 and long time or T = 300 K and can go through each other without scattering in their collisions. In these cases its lifetime is, at least, 120 ps at 300 K, in which the soliton can travel over about 700 amino acid residues. This result is consistent with analytic result obtained by quantum perturbed theory in this model. In the meanwhile, the influences of structure disorder of a-helix protein molecules, including the inhomogeneous distribution of amino acids with different masses and fluctuations of spring constant, dipole-dipole interaction, exciton-phonon coupling constant and diagonal disorder, on the solitons are also studied by the fourth-order Runge-Kutta method. The results show that the soliton still is very robust against the structure disorders and thermal perturbation of proteins at biological temperature 300 K. Therefore we can conclude that the new soliton in the a-helix protein molecules with three channels is a possible carrier of bio-energy transport and the improved model is possibly a candidate for the mechanism of this transport.展开更多
We propose a new flame index for the transported probability density function(PDF) method. The flame index uses mixing flux projections of Lagrangian particles on mixture fraction and progress variable directions as t...We propose a new flame index for the transported probability density function(PDF) method. The flame index uses mixing flux projections of Lagrangian particles on mixture fraction and progress variable directions as the metrics to identify the combustion mode, with the Burke-Schumann solution as a reference. A priori validation of the flame index is conducted with a series of constructed turbulent partially premixed reactors. It indicates that the proposed flame index is able to identify the combustion mode based on the subgrid mixing information. The flame index is then applied the large eddy simulation/PDF datasets of turbulent partially premixed jet flames. Results show that the flame index separate different combustion modes and extinction correctly. The proposed flame index provides a promising tool to analyze and model the partially premixed flames adaptively.展开更多
This paper presents overview of new features so far prepared for new version of spectral analysis tool SPLAT-VO that allows to retrieve a large amount of spectra(and other data) based on its characteristics by detaile...This paper presents overview of new features so far prepared for new version of spectral analysis tool SPLAT-VO that allows to retrieve a large amount of spectra(and other data) based on its characteristics by detailed querying a virtual observatory s resources. The overview is focused on enhancements of user experience, work with simple application messaging protocol(SAMP) and other interoperability that improves work with global list of spectra, plot window and analysis menu.展开更多
Successful nerve regeneration requires not only that neurons reconstruct new axons distal to the site of injury,but also those growing axons must navigate through the neuropil to make appropriate synaptic connections ...Successful nerve regeneration requires not only that neurons reconstruct new axons distal to the site of injury,but also those growing axons must navigate through the neuropil to make appropriate synaptic connections with target cells.While this is an imposing task for the thousands of axons that may occupy a regenerating nerve in the peripheral nervous system or a tract inthe central nervous system, the billions of neurons in the developing brain must accomplish similar tasks making connections that number in the trillions. How do neurons do this？展开更多
Melanie C.Green and Timothy C.Brock have proposed their transportation-imagery model of narrative persuasion.They argue that a narrative can evoke imagery in readers'mind and then transport readers into the narrat...Melanie C.Green and Timothy C.Brock have proposed their transportation-imagery model of narrative persuasion.They argue that a narrative can evoke imagery in readers'mind and then transport readers into the narrative world the author has created,in the course of which the author can persuade readers of the beliefs he's put into the narrative.This paper employs this model to rethink how Arthur Conan Doyle persuades his readers of British imperialism in his"The Speckled Band".First,this model considers the vividness of the narrative and readers'participatory response as key factors in readers'transportation.The narratives of"The Speckled Band"are picturesque,and Sherlock Holmes'inferential process has reinforced readers'participatory response.On the other hand,detective fiction usually has the theme of how the detective/law and order beats the criminal/chaos.That is,Doyle persuades his readers that the British Empire will prevail in"The Speckled Band"when Holmes,representing the British imperialism,solves the case and kills Dr.Roylott,who represents the evil and savagery in the British colony.According to Green and Brock's model,it simply means that there are two narratives(i.e.,one is about how the law of the British Empire is challenged,and the other is about how the British Empire's stability is restored),and two complementary transportations before Doyle can successfully persuades his readers.However,if we closely read"'The Speckled Band",we can learn that Holmes,who should have represented British law,is guilty of trespassing or taking the law into his own hands.In other words,the complementarity of the two transportations is compromised.Thus,we can conclude that it is highly questionable whether or not Doyle can transport his readers into the bosom of the British Empire.展开更多
<strong>Objective:</strong> In Japan, red blood cell (RBC) solution is usually transported by car from a medical institution to the patient’s house for home transfusion. However, there are no regulations ...<strong>Objective:</strong> In Japan, red blood cell (RBC) solution is usually transported by car from a medical institution to the patient’s house for home transfusion. However, there are no regulations for transporting blood by car in the medical setting. Therefore, we assessed and compared the methods (containers) used for transporting the RBC solution by car. <strong>Materials and Methods:</strong> Irradiated RBC solution samples (280 mL) supplied by the Japan Red Cross Society were each divided into two bags. The quality of blood transported by car (1 - 2 hours) in an active transport refrigerator (ATR) (control group) was compared with that transported in a cooler, or styrofoam box (study group). We tested the hemolytic effects of transportation by car, storage, and filtration through a transfusion set on the lactate dehydrogenase (LD) levels in the RBC solutions. <strong>Results:</strong> Post-filtered LD levels were significantly higher in the RBC solutions transported in a cooler-box with inadequate temperature control when compared to those transported in an ATR with optimal temperature control. However, under conditions of optimal temperature control, the post-filtered LD levels were comparable in the control and study (both cooler and styrofoam boxes) group RBC solutions. <strong>Conclusion:</strong> Temperature management is critical for the maintenance of the quality of the RBC solution transported by car.展开更多
Detecting pavement cracks is critical for road safety and infrastructure management.Traditional methods,relying on manual inspection and basic image processing,are time-consuming and prone to errors.Recent deep-learni...Detecting pavement cracks is critical for road safety and infrastructure management.Traditional methods,relying on manual inspection and basic image processing,are time-consuming and prone to errors.Recent deep-learning(DL)methods automate crack detection,but many still struggle with variable crack patterns and environmental conditions.This study aims to address these limitations by introducing the Masker Transformer,a novel hybrid deep learning model that integrates the precise localization capabilities of Mask Region-based Convolutional Neural Network(Mask R-CNN)with the global contextual awareness of Vision Transformer(ViT).The research focuses on leveraging the strengths of both architectures to enhance segmentation accuracy and adaptability across different pavement conditions.We evaluated the performance of theMaskerTransformer against other state-of-theartmodels such asU-Net,TransformerU-Net(TransUNet),U-NetTransformer(UNETr),SwinU-NetTransformer(Swin-UNETr),You Only Look Once version 8(YoloV8),and Mask R-CNN using two benchmark datasets:Crack500 and DeepCrack.The findings reveal that the MaskerTransformer significantly outperforms the existing models,achieving the highest Dice SimilarityCoefficient(DSC),precision,recall,and F1-Score across both datasets.Specifically,the model attained a DSC of 80.04%on Crack500 and 91.37%on DeepCrack,demonstrating superior segmentation accuracy and reliability.The high precision and recall rates further substantiate its effectiveness in real-world applications,suggesting that the Masker Transformer can serve as a robust tool for automated pavement crack detection,potentially replacing more traditional methods.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts...The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.展开更多
Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen so...Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.展开更多
The ocean serves as a repository for various types of artificial nanoparticles.Nanoplastics(NPs)and nano zinc oxide(nZnO),which are frequently employed in personal care products and food packaging materials,are likely...The ocean serves as a repository for various types of artificial nanoparticles.Nanoplastics(NPs)and nano zinc oxide(nZnO),which are frequently employed in personal care products and food packaging materials,are likely simultaneously released and eventually into the ocean with surface runoff.Therefore,their mutual influence and shared destiny in marine environment cannot be ignored.This study examined how nanomaterials interacted and transported through sea sand in various salinity conditions.Results showed that NPs remained dispersed in brine,while nZnO formed homoaggregates.In seawater of 35 practical salinity units(PSU),nZnO formed heteroaggregates with NPs,inhibiting NPs mobility and decreasing the recovered mass percentage(Meff)from 24.52%to 12.65%.In 3.5 PSU brackish water,nZnO did not significantly aggregate with NPs,and thus barely affected their mobility.However,NPs greatly enhanced nZnO transport with Meff increasing from 14.20%to 25.08%,attributed to the carrier effect of higher mobility NPs.Cotransport from brackishwater to seawater was simulated in salinity change experiments and revealed a critical salinity threshold of 10.4 PSU,below which the mobility of NPs was not affected by coexisting nZnO and above which nZnO strongly inhibited NP transport.This study highlights the importance of considering the mutual influence and shared destiny of artificial nanoparticles in the marine environment and how their interaction and cotransport are dependent on changes in seawater salinity.展开更多
文摘A key pathological feature of Parkinson’s disease(PD)is that lysosomes are overwhelmed with cellular materials that need to be degraded and cleared.While the build-up of protein is characteristic of neurodegenerative diseases such as PD and Alzheimer’s disease(AD)and is thought to reflect lysosome dysfunction,lipid accumulation may also contribute to and be indicative of severe lysosomal dysfunction.Much is known about the detrimental effects of glucosylceramide accumulation in PD lysosomes.
基金supported by a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center(to PKS)the Rutgers University Startup Fund(to PKS).
文摘Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.
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support provided by the National Natural Science Foundation of China(Grant No.31701939)National Natural Science Foundation of Shaanxi province,China(Grant No.2019JQ-324)+1 种基金National Key R&D Program of China(Grant No.2018YFD0100704)the Modern Agro-industry Technology Research System of China(Grant No.CARS-25).
文摘Proline accumulation has been shown to occur in plants in response to various environmental stresses.Although proline metabolismrelated genes have been functionally characterized,the inter-organ transport of proline in stressed plants remains unclear.In this study,free proline was detected with significant accumulations in the roots,stems,and leaves of watermelon drought-tolerant germplasm M08 and drought-susceptible line Y34 under drought stress.Expression profiling and enzyme activity measurements revealed that ClP5CS1 gene,rather than its paralog ClP5CS2,mainly contributes to the proline synthesis in leaves via the Glu pathway.Additionally,over-expression of the ClP5CS genes significantly enhanced the drought tolerance of transgenic Arabidopsis lines.Furthermore,we confirmed that proline is mainly synthesized in leaves and transported to roots in watermelon under drought stress.Transcriptome and expression analyses revealed that the genes involved in proline metabolism exhibited different expression levels.Specifically,ClP5CS1 was upregulated in leaves and roots,while ClP5CS2 was downregulated under drought stress.Also,415 and 362 differently expressed TFs were identified in roots and leaves,respectively,with the majority upregulated in the former.Ultimately,a model for proline metabolism was proposed.The findings of this study provided new insights into the biosynthesis,transport,and regulatory mechanism of drought-induced proline in plants.
基金supported by the National Key Research and Development Program of China(No.2017YFB0306103)R&D Program in Key Fields of Guangdong Province(No.2019B010936001)+2 种基金the National Natural Science Foundation of China(Grant No.51901175)the China Postdoctoral Science Foundation funded project(No.2019M653602)the National Program for Support of Top-notch Young Professionals。
文摘Plasma spray-physical vapor deposition(PS-PVD)has exhibited the potential ability to prepare columnar structures for advanced thermal barrier coatings(TBCs).The coating structure is nominally affected by operating parameters,but it is controlled by the type of deposition unit actually and essentially.In order to realize the columnar structure deposited by gaseous phase units,the transition behavior of gaseous phase units to clusters must be fundamentally understood.This work investigated the transport process of gaseous phase units in the PS-PVD near-substrate boundary layer along with the condensation behavior.The Monte Carlo method was used to examine the transport process and condensation behavior of gaseous phase units under different scale boundary layers.Simulation results show that it is easier to form more numerous larger clusters at the edge of the plasma jet than at the center.Based on the understanding of the changes in deposition unit caused by the condensation of gaseous phase in the near-substrate boundary layer of PS-PVD,an outlook towards TBCs with different structures is presented.And it is in good agreement with the experimental data.
基金The project supported by National Natural Science Foundation of China under Grant No.19974034
文摘We study the stabilization of the soliton transported bio-energy by the dynamic equations in the improved Davydov theory from four aspects containing the feature of free motion and states of the soliton at the long-time motion and at biological temperature 300 K and behaviors of collision of the solitons by Runge–Kutta method and physical parameter values appropriate to the α-helix protein molecules. We prove that the new solitons can move without dispersion at a constant speed retaining its shape and energy in free and long-time motions and can go through each other without scattering. If considering further influence of the temperature effect of heat bath on the soliton, it is still thermally stable at biological temperature 300 K and in a time as long as 300 ps and amino acid spacings as large as 400, which shows that the lifetime of the new soliton is at least 300 ps, which is consistent with analytic result obtained by quantum perturbation theory. These results exhibit that the new soliton is a possible carrier of bio-energy transport and the improved model is possibly a candidate for the mechanism of this transport.
文摘To demonstrate the distribution and expression of heat shock proteins (HSPs) in the liver, five kinds of HSPs, namely HSP70, HSP72, HSP86, HSP90 and HSP27 were determined after a long distance transport using immunohistochemistry and Western blot. All five HSPs were regularly detected in the liver of both the transported and the control group. Both nuclear and cytoplasmic labeling was present in hepatic cells; however, localization of HSPs was quite different in hepatocytes. The majority of HSP70, HSP72 and HSP27 appeared to predominate in cytoplasm of the hepatocytes. Nuclear signals of HSP90 and HSP86 were most prominent in hepatocytes in which immunostaining in the cytoplasm was relatively weak compared with that in the nucleus. There was subjectively lower staining in the edge of hepatic labule, and lower numbers of HSPs labeled hepatic cells corresponded to light microscopic lesions. The obvious inductions of some HSPs were detected in the liver, especially the HSP90(P<0.01) which belongs to the HSP90 family. However, the obvious reductions of HSP86(P<0.05), which belong to the HSP90 family, and HSP27 (P <0.05), which belong to small families, were detected in stressed pig liver after six hours of long distance transportation.
基金The project supported by National Natural Science Foundation of China under Grant No. 19974034
文摘We study numerically the propagating properties of soliton-transported bio-energy excited in the a-helix protein molecules with three channels in the cases of the short-time and long-time motions and its features of collision at temperature T = 0 and biological temperature T = 300 K by the dynamic equations in the improved Davydov theory and fourth-order Runge-Kutta method, respectively. From these simulation experiments we see that the new solitons in the improved model can move without dispersion at a constant speed retaining its shape and energy in the cases of motion of both short-time or T = 0 and long time or T = 300 K and can go through each other without scattering in their collisions. In these cases its lifetime is, at least, 120 ps at 300 K, in which the soliton can travel over about 700 amino acid residues. This result is consistent with analytic result obtained by quantum perturbed theory in this model. In the meanwhile, the influences of structure disorder of a-helix protein molecules, including the inhomogeneous distribution of amino acids with different masses and fluctuations of spring constant, dipole-dipole interaction, exciton-phonon coupling constant and diagonal disorder, on the solitons are also studied by the fourth-order Runge-Kutta method. The results show that the soliton still is very robust against the structure disorders and thermal perturbation of proteins at biological temperature 300 K. Therefore we can conclude that the new soliton in the a-helix protein molecules with three channels is a possible carrier of bio-energy transport and the improved model is possibly a candidate for the mechanism of this transport.
基金sponsored by King Abdullah University of Science and Technology(KAUST)the National Natural Science Foundation of China(Grant No.91841302)。
文摘We propose a new flame index for the transported probability density function(PDF) method. The flame index uses mixing flux projections of Lagrangian particles on mixture fraction and progress variable directions as the metrics to identify the combustion mode, with the Burke-Schumann solution as a reference. A priori validation of the flame index is conducted with a series of constructed turbulent partially premixed reactors. It indicates that the proposed flame index is able to identify the combustion mode based on the subgrid mixing information. The flame index is then applied the large eddy simulation/PDF datasets of turbulent partially premixed jet flames. Results show that the flame index separate different combustion modes and extinction correctly. The proposed flame index provides a promising tool to analyze and model the partially premixed flames adaptively.
基金supported by Agency of the Czech Republic-GACR(No.P103/13/08195S)the Development of Human Resources in Research and Development of Latest Soft Computing Methods and Their Application in Practical Project,Operational Programm Education for Competitiveness(No.CZ.1.07/2.3.00/20.0072)+1 种基金ESF State Budget of the Czech Republic,SGS(No.SP2013/114)VBTechnical University of Ostrava,Czech Republic
文摘This paper presents overview of new features so far prepared for new version of spectral analysis tool SPLAT-VO that allows to retrieve a large amount of spectra(and other data) based on its characteristics by detailed querying a virtual observatory s resources. The overview is focused on enhancements of user experience, work with simple application messaging protocol(SAMP) and other interoperability that improves work with global list of spectra, plot window and analysis menu.
文摘Successful nerve regeneration requires not only that neurons reconstruct new axons distal to the site of injury,but also those growing axons must navigate through the neuropil to make appropriate synaptic connections with target cells.While this is an imposing task for the thousands of axons that may occupy a regenerating nerve in the peripheral nervous system or a tract inthe central nervous system, the billions of neurons in the developing brain must accomplish similar tasks making connections that number in the trillions. How do neurons do this？
文摘Melanie C.Green and Timothy C.Brock have proposed their transportation-imagery model of narrative persuasion.They argue that a narrative can evoke imagery in readers'mind and then transport readers into the narrative world the author has created,in the course of which the author can persuade readers of the beliefs he's put into the narrative.This paper employs this model to rethink how Arthur Conan Doyle persuades his readers of British imperialism in his"The Speckled Band".First,this model considers the vividness of the narrative and readers'participatory response as key factors in readers'transportation.The narratives of"The Speckled Band"are picturesque,and Sherlock Holmes'inferential process has reinforced readers'participatory response.On the other hand,detective fiction usually has the theme of how the detective/law and order beats the criminal/chaos.That is,Doyle persuades his readers that the British Empire will prevail in"The Speckled Band"when Holmes,representing the British imperialism,solves the case and kills Dr.Roylott,who represents the evil and savagery in the British colony.According to Green and Brock's model,it simply means that there are two narratives(i.e.,one is about how the law of the British Empire is challenged,and the other is about how the British Empire's stability is restored),and two complementary transportations before Doyle can successfully persuades his readers.However,if we closely read"'The Speckled Band",we can learn that Holmes,who should have represented British law,is guilty of trespassing or taking the law into his own hands.In other words,the complementarity of the two transportations is compromised.Thus,we can conclude that it is highly questionable whether or not Doyle can transport his readers into the bosom of the British Empire.
文摘<strong>Objective:</strong> In Japan, red blood cell (RBC) solution is usually transported by car from a medical institution to the patient’s house for home transfusion. However, there are no regulations for transporting blood by car in the medical setting. Therefore, we assessed and compared the methods (containers) used for transporting the RBC solution by car. <strong>Materials and Methods:</strong> Irradiated RBC solution samples (280 mL) supplied by the Japan Red Cross Society were each divided into two bags. The quality of blood transported by car (1 - 2 hours) in an active transport refrigerator (ATR) (control group) was compared with that transported in a cooler, or styrofoam box (study group). We tested the hemolytic effects of transportation by car, storage, and filtration through a transfusion set on the lactate dehydrogenase (LD) levels in the RBC solutions. <strong>Results:</strong> Post-filtered LD levels were significantly higher in the RBC solutions transported in a cooler-box with inadequate temperature control when compared to those transported in an ATR with optimal temperature control. However, under conditions of optimal temperature control, the post-filtered LD levels were comparable in the control and study (both cooler and styrofoam boxes) group RBC solutions. <strong>Conclusion:</strong> Temperature management is critical for the maintenance of the quality of the RBC solution transported by car.
文摘Detecting pavement cracks is critical for road safety and infrastructure management.Traditional methods,relying on manual inspection and basic image processing,are time-consuming and prone to errors.Recent deep-learning(DL)methods automate crack detection,but many still struggle with variable crack patterns and environmental conditions.This study aims to address these limitations by introducing the Masker Transformer,a novel hybrid deep learning model that integrates the precise localization capabilities of Mask Region-based Convolutional Neural Network(Mask R-CNN)with the global contextual awareness of Vision Transformer(ViT).The research focuses on leveraging the strengths of both architectures to enhance segmentation accuracy and adaptability across different pavement conditions.We evaluated the performance of theMaskerTransformer against other state-of-theartmodels such asU-Net,TransformerU-Net(TransUNet),U-NetTransformer(UNETr),SwinU-NetTransformer(Swin-UNETr),You Only Look Once version 8(YoloV8),and Mask R-CNN using two benchmark datasets:Crack500 and DeepCrack.The findings reveal that the MaskerTransformer significantly outperforms the existing models,achieving the highest Dice SimilarityCoefficient(DSC),precision,recall,and F1-Score across both datasets.Specifically,the model attained a DSC of 80.04%on Crack500 and 91.37%on DeepCrack,demonstrating superior segmentation accuracy and reliability.The high precision and recall rates further substantiate its effectiveness in real-world applications,suggesting that the Masker Transformer can serve as a robust tool for automated pavement crack detection,potentially replacing more traditional methods.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
文摘The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.
基金supported by National Key Research and Development Program of China(Grant No.2021YFE0115200)the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Grant No.U22A20356).
文摘Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
基金supported by the National Natural Science Foundation of China (No.22176148)the Shanghai Rising-Star Program (No.23QB1406400)+1 种基金the Fundamental Research Funds for the Central Universities of Tongji University (No.2023-3-ZD-02)supported by the program INTPART (Plastic Pollution,No.275172)funded by the Research Council of Norway.
文摘The ocean serves as a repository for various types of artificial nanoparticles.Nanoplastics(NPs)and nano zinc oxide(nZnO),which are frequently employed in personal care products and food packaging materials,are likely simultaneously released and eventually into the ocean with surface runoff.Therefore,their mutual influence and shared destiny in marine environment cannot be ignored.This study examined how nanomaterials interacted and transported through sea sand in various salinity conditions.Results showed that NPs remained dispersed in brine,while nZnO formed homoaggregates.In seawater of 35 practical salinity units(PSU),nZnO formed heteroaggregates with NPs,inhibiting NPs mobility and decreasing the recovered mass percentage(Meff)from 24.52%to 12.65%.In 3.5 PSU brackish water,nZnO did not significantly aggregate with NPs,and thus barely affected their mobility.However,NPs greatly enhanced nZnO transport with Meff increasing from 14.20%to 25.08%,attributed to the carrier effect of higher mobility NPs.Cotransport from brackishwater to seawater was simulated in salinity change experiments and revealed a critical salinity threshold of 10.4 PSU,below which the mobility of NPs was not affected by coexisting nZnO and above which nZnO strongly inhibited NP transport.This study highlights the importance of considering the mutual influence and shared destiny of artificial nanoparticles in the marine environment and how their interaction and cotransport are dependent on changes in seawater salinity.
