Eighty-two patients with supraventricular tachycardia undergoing radiofrequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability (PAG) and thr...Eighty-two patients with supraventricular tachycardia undergoing radiofrequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability (PAG) and thromboxane B 2(TXB 2) of the blood samples. Patients were divided into aspirin group A, ticlopidine group B, aspirin+ticlopidine group C and control group D. PAG and TXB 2 were increased clearly after RFCA in all groups (P<0.001). Treatment with aspirin or ticlopidine before operation could reduce the platelet aggregability caused by RFCA and the joint effect of two drugs(change rate of group A:52.51±12.51%; group B:54.78±11.27%;group C: 30.51±10.59%;group D:91.75±21.43%; P<0.05)was studied. The much decreased platelet aggregability after antiplatelet therapy was evidence of the potential benefit of the treatment in preventing thromboembolism after ablation. Pretreatment with aspirin and ticlopidine together is a good way to decrease palatelet aggregability after RFCA.展开更多
Neurons are highly polarized cells with axons reaching over a meter long in adult humans.To survive and maintain their proper function,neurons depend on specific mechanisms that regulate spatiotemporal signaling and m...Neurons are highly polarized cells with axons reaching over a meter long in adult humans.To survive and maintain their proper function,neurons depend on specific mechanisms that regulate spatiotemporal signaling and metabolic events,which need to be carried out at the right place,time,and intensity.Such mechanisms include axonal transport,local synthesis,and liquid-liquid phase separations.Alterations and malfunctions in these processes are correlated to neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS).展开更多
The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic prote...The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants.Senile systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the myocardium.Regarding hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).展开更多
Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord,leading to muscle weakness,paralysis,and ultimately death(C...Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord,leading to muscle weakness,paralysis,and ultimately death(Cleveland and Rothstein,2001).Frontotemporal lobar degeneration(FTLD)is a neurodegenerative disease affecting the frontal and temporal lobes of the brain,leading to changes in behavior,personality,and language(Van Langenhove et al.,2012).Both ALS and FTLD are classified as proteinopathies in which abnormal protein aggregation and accumulation in neurons contribute to the disease pathogenesis.Fused in sarcoma(FUS)is a DNA/RNA-binding protein involved in various cellular processes,including transcriptional regulation,RNA splicing,and DNA repair.Mutations in the FUS gene have been linked to familial ALS,highlighting the importance of FUS in the disease pathogenesis(Vance et al.,2009).In ALS and FTLD,aberrant post-translational modifications(PTMs)of FUS,such as phosphorylation,acetylation,and methylation,have been implicated in the promotion of FUS aggregation and neurotoxicity(Choi et al.,2023).Therefore,understanding the regulatory mechanisms of FUS PTMs is crucial for developing targeted therapies against these diseases.展开更多
Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to prote...Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.展开更多
The success rate of apexification is primarily determined by multiple factors,including the material used,the size of the open apex compared to the length of the root,and the technique used in each case.The main objec...The success rate of apexification is primarily determined by multiple factors,including the material used,the size of the open apex compared to the length of the root,and the technique used in each case.The main objective of this review was to provide an update on the present management of open apex to identify factors and circumstances that may influence the success of apexification using different materials and techniques.Future research on apexification should focus on how to treat open apices with wide periapical lesions without surgery.Previously,the predictability of these parameters with non-surgical procedures was uncertain,but now,with the use of a dental operating microscope,it has become more predictable.Another reason could be that extra visits are no longer required due to major advances in the armamentarium and materials used for apexification.展开更多
Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau pro...Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.展开更多
Straw return is a promising strategy for managing soil organic carbon(SOC)and improving yield stability.However,the optimal straw return strategy for sustainable crop production in the wheat(Triticum aestivum L.)-cott...Straw return is a promising strategy for managing soil organic carbon(SOC)and improving yield stability.However,the optimal straw return strategy for sustainable crop production in the wheat(Triticum aestivum L.)-cotton(Gossypium hirsutum L.)cropping system remains uncertain.The objective of this study was to quantify the long-term(10 years)impact of carbon(C)input on SOC sequestration,soil aggregation and crop yields in a wheat-cotton cropping system in the Yangtze River Valley,China.Five treatments were arranged with a single-factor randomized design as follows:no straw return(Control),return of wheat straw only(Wt),return of cotton straw only(Ct),return of 50%wheat and 50%cotton straw(Wh-Ch)and return of 100%wheat and 100%cotton straw(Wt-Ct).In comparison to the Control,the SOC content increased by 8.4 to 20.2%under straw return.A significant linear positive correlation between SOC sequestration and C input(1.42-7.19 Mg ha^(−1)yr^(−1))(P<0.05)was detected.The percentages of aggregates of sizes>2 and 1-2 mm at the 0-20 cm soil depth were also significantly elevated under straw return,with the greatest increase of the aggregate stability in the Wt-Ct treatment(28.1%).The average wheat yields increased by 12.4-36.0%and cotton yields increased by 29.4-73.7%,and significantly linear positive correlations were also detected between C input and the yields of wheat and cotton.The average sustainable yield index(SYI)reached a maximum value of 0.69 when the C input was 7.08 Mg ha^(−1)yr^(−1),which was close to the maximum value(SYI of 0.69,C input of 7.19 Mg ha^(−1)yr^(-1))in the Wt-Ct treatment.Overall,the return of both wheat and cotton straw was the best strategy for improving SOC sequestration,soil aggregation,yields and their sustainability in the wheat-cotton rotation system.展开更多
Recently, there have been some attempts of Transformer in 3D point cloud classification. In order to reduce computations, most existing methods focus on local spatial attention,but ignore their content and fail to est...Recently, there have been some attempts of Transformer in 3D point cloud classification. In order to reduce computations, most existing methods focus on local spatial attention,but ignore their content and fail to establish relationships between distant but relevant points. To overcome the limitation of local spatial attention, we propose a point content-based Transformer architecture, called PointConT for short. It exploits the locality of points in the feature space(content-based), which clusters the sampled points with similar features into the same class and computes the self-attention within each class, thus enabling an effective trade-off between capturing long-range dependencies and computational complexity. We further introduce an inception feature aggregator for point cloud classification, which uses parallel structures to aggregate high-frequency and low-frequency information in each branch separately. Extensive experiments show that our PointConT model achieves a remarkable performance on point cloud shape classification. Especially, our method exhibits 90.3% Top-1 accuracy on the hardest setting of ScanObjectN N. Source code of this paper is available at https://github.com/yahuiliu99/PointC onT.展开更多
Red blood cells(RBCs)are the most abundant human blood cells.RBC aggregation and deformation strongly determine blood viscosity which impacts hemorheology and microcirculation.In turn,RBC properties depend on di®...Red blood cells(RBCs)are the most abundant human blood cells.RBC aggregation and deformation strongly determine blood viscosity which impacts hemorheology and microcirculation.In turn,RBC properties depend on di®erent endogenous and exogenous factors.One such factor is nitric oxide(NO),which is mainly produced by endothelial cells(EC)from L-arginine amino acid in the circulatory system.Since the mechanisms of the RBC-endothelium interplay are not clear up to date and considering its possible clinical importance,the aims of this study are to investigate in vitro:(1)The effect of L-arginine induced NO on RBC aggregation and adhesion to endothelium;(2)the NO e®ect on RBC aggregation and deformation induced by L-arginine and sodium nitroprusside without the presence of endothelium in the samples.The RBC aggregation and adhesion to a monolayer of EC were studied using optical tweezers(OT).The RBC deformability and aggregation without endothelium in the samples were studied using the flow chamber method and Myrenne aggregometer.We confirmed that NO increases deformability and decreases aggregation of RBCs.We showed that the soluble guanylate cyclase pathway appears to be the only NO signaling pathway involved.In the samples with the endothelium,the "bell-shaped"dependence of RBC aggregation force on L-arginine concentration was observed,which improves our knowledge about the process of NO production by endothelium.Additionally,data related to L-arginine accumulation by endothelium were obtained:Necessity of the presence of extracellular L-arginine stated by other authors was put under question.In our study,NO decreased the RBC-endothelium adhesion,however,the tendency appeared to be weak and was not confirmed in another set of experiments.To our knowledge,this is the first attempt to measure the forces of RBC adhesion to endothelium monolayer with OT.展开更多
Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of thera...Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.展开更多
Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signali...Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.展开更多
Federated Learning(FL),a burgeoning technology,has received increasing attention due to its privacy protection capability.However,the base algorithm FedAvg is vulnerable when it suffers from so-called backdoor attacks...Federated Learning(FL),a burgeoning technology,has received increasing attention due to its privacy protection capability.However,the base algorithm FedAvg is vulnerable when it suffers from so-called backdoor attacks.Former researchers proposed several robust aggregation methods.Unfortunately,due to the hidden characteristic of backdoor attacks,many of these aggregation methods are unable to defend against backdoor attacks.What's more,the attackers recently have proposed some hiding methods that further improve backdoor attacks'stealthiness,making all the existing robust aggregation methods fail.To tackle the threat of backdoor attacks,we propose a new aggregation method,X-raying Models with A Matrix(XMAM),to reveal the malicious local model updates submitted by the backdoor attackers.Since we observe that the output of the Softmax layer exhibits distinguishable patterns between malicious and benign updates,unlike the existing aggregation algorithms,we focus on the Softmax layer's output in which the backdoor attackers are difficult to hide their malicious behavior.Specifically,like medical X-ray examinations,we investigate the collected local model updates by using a matrix as an input to get their Softmax layer's outputs.Then,we preclude updates whose outputs are abnormal by clustering.Without any training dataset in the server,the extensive evaluations show that our XMAM can effectively distinguish malicious local model updates from benign ones.For instance,when other methods fail to defend against the backdoor attacks at no more than 20%malicious clients,our method can tolerate 45%malicious clients in the black-box mode and about 30%in Projected Gradient Descent(PGD)mode.Besides,under adaptive attacks,the results demonstrate that XMAM can still complete the global model training task even when there are 40%malicious clients.Finally,we analyze our method's screening complexity and compare the real screening time with other methods.The results show that XMAM is about 10–10000 times faster than the existing methods.展开更多
Tillage practices during the fallow period benefit water storage and yield in dryland wheat crops.However,there is currently no clarity on the responses of soil organic carbon(SOC),total nitrogen(TN),and available nut...Tillage practices during the fallow period benefit water storage and yield in dryland wheat crops.However,there is currently no clarity on the responses of soil organic carbon(SOC),total nitrogen(TN),and available nutrients to tillage practices within the growing season.This study evaluated the effects of three tillage practices(NT,no tillage;SS,subsoil tillage;DT,deep tillage)over five years on soil physicochemical properties.Soil samples at harvest stage from the fifth year were analyzed to determine the soil aggregate and aggregate-associated C and N fractions.The results indicated that SS and DT improved grain yield,straw biomass and straw carbon return of wheat compared with NT.In contrast to DT and NT,SS favored SOC and TN concentrations and stocks by increasing the soil organic carbon sequestration rate(SOCSR)and soil nitrogen sequestration rate(TNSR)in the 0-40 cm layer.Higher SOC levels under SS and NT were associated with greater aggregate-associated C fractions,while TN was positively associated with soluble organic nitrogen(SON).Compared with DT,the NT and SS treatments improved soil available nutrients in the 0-20 cm layer.These findings suggest that SS is an excellent practice for increasing soil carbon,nitrogen and nutrient availability in dryland wheat fields in North China.展开更多
α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and...α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.展开更多
Aggregation of species with similar ecological properties is one of the effective methods to simplify food web researches.However,species aggregation will affect not only the complexity of modeling process but also th...Aggregation of species with similar ecological properties is one of the effective methods to simplify food web researches.However,species aggregation will affect not only the complexity of modeling process but also the accuracy of models’outputs.Selection of aggregation methods and the number of trophospecies are the keys to study the simplification of food web.In this study,three aggregation methods,including taxonomic aggregation(TA),structural equivalence aggregation(SEA),and self-organizing maps(SOM),were analyzed and compared with the linear inverse model–Markov Chain Monte Carlo(LIM-MCMC)model.Impacts of aggregation methods and trophospecies number on food webs were evaluated based on the robustness and unitless of ecological net-work indices.Results showed that aggregation method of SEA performed better than the other two methods in estimating food web structure and function indices.The effects of aggregation methods were driven by the differences in species aggregation principles,which will alter food web structure and function through the redistribution of energy flow.According to the results of mean absolute percentage error(MAPE)which can be applied to evaluate the accuracy of the model,we found that MAPE in food web indices will increase with the reducing trophospecies number,and MAPE in food web function indices were smaller and more stable than those in food web structure indices.Therefore,trade-off between simplifying food webs and reflecting the status of ecosystem should be con-sidered in food web studies.These findings highlight the importance of aggregation methods and trophospecies number in the analy-sis of food web simplification.This study provided a framework to explore the extent to which food web models are affected by dif-ferent species aggregation,and will provide scientific basis for the construction of food webs.展开更多
A simplex centroid design method was employed to design the gradation of recycled coarse aggregate.The bulk density was measured while the specific surface area and average excess paste thickness were calculated with ...A simplex centroid design method was employed to design the gradation of recycled coarse aggregate.The bulk density was measured while the specific surface area and average excess paste thickness were calculated with different gradations.The fluidity,dynamic yield stress,static yield stress,printed width,printed inclination,compressive strength and ultrasonic wave velocity of 3D printed recycled aggregate concrete(3DPRAC)were further studied.The experimental results demonstrate that,with the increase of small-sized aggregate(4.75-7 mm)content,the bulk density initially increases and then decreases,and the specific surface area gradually increases.The average excess paste thickness fluctuates with both bulk density and specific surface area.The workability of 3DPRAC is closely related to the average excess paste thickness.With an increase in average paste thickness,there is a gradual decrease in dynamic yield stress,static yield stress and printed inclination,accompanied by an increase in fluidity and printed width.The mechanical performance of 3DPRAC closely correlates with the bulk density.With an increase in the bulk density,there is an increase in the ultrasonic wave velocity,accompanied by a slight increase in the compressive strength and a significant decrease in the anisotropic coefficient.Furthermore,an index for buildability failure of 3DPRAC based on the average excess paste thickness is proposed.展开更多
Underwater pulse waveform recognition is an important method for underwater object detection.Most existing works focus on the application of traditional pattern recognition methods,which ignore the time-and space-vary...Underwater pulse waveform recognition is an important method for underwater object detection.Most existing works focus on the application of traditional pattern recognition methods,which ignore the time-and space-varying characteristics in sound propagation channels and cannot easily extract valuable waveform features.Sound propagation channels in seawater are time-and space-varying convolutional channels.In the extraction of the waveform features of underwater acoustic signals,the effect of high-accuracy underwater acoustic signal recognition is identified by eliminating the influence of time-and space-varying convolutional channels to the greatest extent possible.We propose a hash aggregate discriminative network(HADN),which combines hash learning and deep learning to minimize the time-and space-varying effects on convolutional channels and adaptively learns effective underwater waveform features to achieve high-accuracy underwater pulse waveform recognition.In the extraction of the hash features of acoustic signals,a discrete constraint between clusters within a hash feature class is introduced.This constraint can ensure that the influence of convolutional channels on hash features is minimized.In addition,we design a new loss function called aggregate discriminative loss(AD-loss).The use of AD-loss and softmax-loss can increase the discriminativeness of the learned hash features.Experimental results show that on pool and ocean datasets,which were collected in pools and oceans,respectively,by using acoustic collectors,the proposed HADN performs better than other comparative models in terms of accuracy and mAP.展开更多
The bioreduction of graphene oxide(GO)using environmentally functional bacteria such as Shewanella represents a green approach to produce reduced graphene oxide(rGO).This process differs from the chemical reduction th...The bioreduction of graphene oxide(GO)using environmentally functional bacteria such as Shewanella represents a green approach to produce reduced graphene oxide(rGO).This process differs from the chemical reduction that involves instantaneous molecular reactions.In bioreduction,the contact of bacterial cells and GO is considered the rate-limiting step.To reveal how the bacteria-GO integration regulates rGO production,the comparative experiments of GO and three Shewanella strains were carried out.Fourier-transform infrared spectroscopy,X-ray photoelectron spectroscopy,Raman spectroscopy,and atomic force microscopy were used to characterize the reduction degree and the aggregation degree.The results showed that a spontaneous aggregation of GO and Shewanella into the condensed entity occurred within 36 h.A positive linear correlation was established,linking three indexes of the aggregation potential,the bacterial reduction ability,and the reduction degree(ID/IG)comprehensively.展开更多
文摘Eighty-two patients with supraventricular tachycardia undergoing radiofrequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability (PAG) and thromboxane B 2(TXB 2) of the blood samples. Patients were divided into aspirin group A, ticlopidine group B, aspirin+ticlopidine group C and control group D. PAG and TXB 2 were increased clearly after RFCA in all groups (P<0.001). Treatment with aspirin or ticlopidine before operation could reduce the platelet aggregability caused by RFCA and the joint effect of two drugs(change rate of group A:52.51±12.51%; group B:54.78±11.27%;group C: 30.51±10.59%;group D:91.75±21.43%; P<0.05)was studied. The much decreased platelet aggregability after antiplatelet therapy was evidence of the potential benefit of the treatment in preventing thromboembolism after ablation. Pretreatment with aspirin and ticlopidine together is a good way to decrease palatelet aggregability after RFCA.
文摘Neurons are highly polarized cells with axons reaching over a meter long in adult humans.To survive and maintain their proper function,neurons depend on specific mechanisms that regulate spatiotemporal signaling and metabolic events,which need to be carried out at the right place,time,and intensity.Such mechanisms include axonal transport,local synthesis,and liquid-liquid phase separations.Alterations and malfunctions in these processes are correlated to neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS).
基金funded by the Spanish Ministry of Science and Innovation(PDC2021-120914-I00)the Universitat Autònoma de Barcelona(PROOF OF CONCEPT 2020)ICREA,ICREA-Academia 2015 and 2020(to SV).
文摘The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants.Senile systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the myocardium.Regarding hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).
基金supported by the BK21 FOUR(Fostering Outstanding Universities for Research)and the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(MOE)and the Ministry of Science and ICT(MSIT)(NRF-2022R1A2C1004204,RS-2023-00219563,2023-DD-UP-0007)by the Soonchunhyang University Research Fund(to KK)。
文摘Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord,leading to muscle weakness,paralysis,and ultimately death(Cleveland and Rothstein,2001).Frontotemporal lobar degeneration(FTLD)is a neurodegenerative disease affecting the frontal and temporal lobes of the brain,leading to changes in behavior,personality,and language(Van Langenhove et al.,2012).Both ALS and FTLD are classified as proteinopathies in which abnormal protein aggregation and accumulation in neurons contribute to the disease pathogenesis.Fused in sarcoma(FUS)is a DNA/RNA-binding protein involved in various cellular processes,including transcriptional regulation,RNA splicing,and DNA repair.Mutations in the FUS gene have been linked to familial ALS,highlighting the importance of FUS in the disease pathogenesis(Vance et al.,2009).In ALS and FTLD,aberrant post-translational modifications(PTMs)of FUS,such as phosphorylation,acetylation,and methylation,have been implicated in the promotion of FUS aggregation and neurotoxicity(Choi et al.,2023).Therefore,understanding the regulatory mechanisms of FUS PTMs is crucial for developing targeted therapies against these diseases.
基金supported by:Fondazione Telethon-Italy(No.GGP19128 to AP)Fondazione Cariplo-Italy(No.2021-1544 to RC)+14 种基金Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica(AriSLA)-Italy(No.MLOpathy to APTarget-RAN to AP)Association Française contre les Myopathies-France(AFM Telethon No.23236 to AP)Kennedy’s Disease Association-USA(2018 grant to RC2020 grant to MG)Ministero dell’Universitàe della Ricerca(MIUR)-Italy(PRIN-Progetti di ricerca di interesse nazionale(No.2017F2A2C5 to APNo.2022EFLFL8 to APNo.2020PBS5MJ to VCNo.2022KSJZF5 to VC)PRIN-Progetti di ricerca di interesse nazionale-bando 2022,PNRR finanziato dall’Unione europea-Next Generation EU,componente M4C2,investimento 1.1(No.P2022B5J32 to RC and No.P20225R4Y5 to VC)CN3:RNA-Codice Proposta:CN_00000041Tematica Sviluppo di terapia genica e farmaci con tecnologia a RNA(Centro Nazionale di Ricerca-CN3 National Center for Gene Therapy and Drugs based on RNA Technology to AP)Progetto Dipartimenti di Eccellenza(to DiSFeB)Ministero della Salute,Agenzia Italiana del Farmaco(AIFA)-Italy(Co_ALS to AP)Universitàdegli Studi di Milano(piano di sviluppo della ricerca(PSR)UNIMI-linea B(to RC and BT).
文摘Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.
文摘The success rate of apexification is primarily determined by multiple factors,including the material used,the size of the open apex compared to the length of the root,and the technique used in each case.The main objective of this review was to provide an update on the present management of open apex to identify factors and circumstances that may influence the success of apexification using different materials and techniques.Future research on apexification should focus on how to treat open apices with wide periapical lesions without surgery.Previously,the predictability of these parameters with non-surgical procedures was uncertain,but now,with the use of a dental operating microscope,it has become more predictable.Another reason could be that extra visits are no longer required due to major advances in the armamentarium and materials used for apexification.
基金supported by the Neural Regeneration Co-innovation Center of Jiangsu Province,Nantong University(to DC)the National Natural Science Foundation of China,Nos.81872853(to DC),81870941(to JHG)the Science and Technology Project of Nantong City,Nos.JC22022022(to FW)and JC2021059(to JM)。
文摘Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.
基金supported by the National Natural Science Foundation of China(32071968)the Jiangsu Agricultural Science and Technology Innovation Fund,China(CX(22)2015))the Jiangsu Collaborative Innovation Center for Modern Crop Production,China。
文摘Straw return is a promising strategy for managing soil organic carbon(SOC)and improving yield stability.However,the optimal straw return strategy for sustainable crop production in the wheat(Triticum aestivum L.)-cotton(Gossypium hirsutum L.)cropping system remains uncertain.The objective of this study was to quantify the long-term(10 years)impact of carbon(C)input on SOC sequestration,soil aggregation and crop yields in a wheat-cotton cropping system in the Yangtze River Valley,China.Five treatments were arranged with a single-factor randomized design as follows:no straw return(Control),return of wheat straw only(Wt),return of cotton straw only(Ct),return of 50%wheat and 50%cotton straw(Wh-Ch)and return of 100%wheat and 100%cotton straw(Wt-Ct).In comparison to the Control,the SOC content increased by 8.4 to 20.2%under straw return.A significant linear positive correlation between SOC sequestration and C input(1.42-7.19 Mg ha^(−1)yr^(−1))(P<0.05)was detected.The percentages of aggregates of sizes>2 and 1-2 mm at the 0-20 cm soil depth were also significantly elevated under straw return,with the greatest increase of the aggregate stability in the Wt-Ct treatment(28.1%).The average wheat yields increased by 12.4-36.0%and cotton yields increased by 29.4-73.7%,and significantly linear positive correlations were also detected between C input and the yields of wheat and cotton.The average sustainable yield index(SYI)reached a maximum value of 0.69 when the C input was 7.08 Mg ha^(−1)yr^(−1),which was close to the maximum value(SYI of 0.69,C input of 7.19 Mg ha^(−1)yr^(-1))in the Wt-Ct treatment.Overall,the return of both wheat and cotton straw was the best strategy for improving SOC sequestration,soil aggregation,yields and their sustainability in the wheat-cotton rotation system.
基金supported in part by the Nationa Natural Science Foundation of China (61876011)the National Key Research and Development Program of China (2022YFB4703700)+1 种基金the Key Research and Development Program 2020 of Guangzhou (202007050002)the Key-Area Research and Development Program of Guangdong Province (2020B090921003)。
文摘Recently, there have been some attempts of Transformer in 3D point cloud classification. In order to reduce computations, most existing methods focus on local spatial attention,but ignore their content and fail to establish relationships between distant but relevant points. To overcome the limitation of local spatial attention, we propose a point content-based Transformer architecture, called PointConT for short. It exploits the locality of points in the feature space(content-based), which clusters the sampled points with similar features into the same class and computes the self-attention within each class, thus enabling an effective trade-off between capturing long-range dependencies and computational complexity. We further introduce an inception feature aggregator for point cloud classification, which uses parallel structures to aggregate high-frequency and low-frequency information in each branch separately. Extensive experiments show that our PointConT model achieves a remarkable performance on point cloud shape classification. Especially, our method exhibits 90.3% Top-1 accuracy on the hardest setting of ScanObjectN N. Source code of this paper is available at https://github.com/yahuiliu99/PointC onT.
基金supported by the Russian Science Foundation Grant No.22-15-00120.
文摘Red blood cells(RBCs)are the most abundant human blood cells.RBC aggregation and deformation strongly determine blood viscosity which impacts hemorheology and microcirculation.In turn,RBC properties depend on di®erent endogenous and exogenous factors.One such factor is nitric oxide(NO),which is mainly produced by endothelial cells(EC)from L-arginine amino acid in the circulatory system.Since the mechanisms of the RBC-endothelium interplay are not clear up to date and considering its possible clinical importance,the aims of this study are to investigate in vitro:(1)The effect of L-arginine induced NO on RBC aggregation and adhesion to endothelium;(2)the NO e®ect on RBC aggregation and deformation induced by L-arginine and sodium nitroprusside without the presence of endothelium in the samples.The RBC aggregation and adhesion to a monolayer of EC were studied using optical tweezers(OT).The RBC deformability and aggregation without endothelium in the samples were studied using the flow chamber method and Myrenne aggregometer.We confirmed that NO increases deformability and decreases aggregation of RBCs.We showed that the soluble guanylate cyclase pathway appears to be the only NO signaling pathway involved.In the samples with the endothelium,the "bell-shaped"dependence of RBC aggregation force on L-arginine concentration was observed,which improves our knowledge about the process of NO production by endothelium.Additionally,data related to L-arginine accumulation by endothelium were obtained:Necessity of the presence of extracellular L-arginine stated by other authors was put under question.In our study,NO decreased the RBC-endothelium adhesion,however,the tendency appeared to be weak and was not confirmed in another set of experiments.To our knowledge,this is the first attempt to measure the forces of RBC adhesion to endothelium monolayer with OT.
基金the financial support received from the Michael J.Fox Foundation through the Target Advancement Program Grant Award (Grant No.MJFF-000649) (to HK)。
文摘Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.
基金supported by the Russian Science Foundation grant(No.22-15-00120)supported by the grant(No.21-2-10-59-1)from the Foundation for the Development of Theoretical Physics and Mathematics BASIS.
文摘Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.
基金Supported by the Fundamental Research Funds for the Central Universities(328202204)。
文摘Federated Learning(FL),a burgeoning technology,has received increasing attention due to its privacy protection capability.However,the base algorithm FedAvg is vulnerable when it suffers from so-called backdoor attacks.Former researchers proposed several robust aggregation methods.Unfortunately,due to the hidden characteristic of backdoor attacks,many of these aggregation methods are unable to defend against backdoor attacks.What's more,the attackers recently have proposed some hiding methods that further improve backdoor attacks'stealthiness,making all the existing robust aggregation methods fail.To tackle the threat of backdoor attacks,we propose a new aggregation method,X-raying Models with A Matrix(XMAM),to reveal the malicious local model updates submitted by the backdoor attackers.Since we observe that the output of the Softmax layer exhibits distinguishable patterns between malicious and benign updates,unlike the existing aggregation algorithms,we focus on the Softmax layer's output in which the backdoor attackers are difficult to hide their malicious behavior.Specifically,like medical X-ray examinations,we investigate the collected local model updates by using a matrix as an input to get their Softmax layer's outputs.Then,we preclude updates whose outputs are abnormal by clustering.Without any training dataset in the server,the extensive evaluations show that our XMAM can effectively distinguish malicious local model updates from benign ones.For instance,when other methods fail to defend against the backdoor attacks at no more than 20%malicious clients,our method can tolerate 45%malicious clients in the black-box mode and about 30%in Projected Gradient Descent(PGD)mode.Besides,under adaptive attacks,the results demonstrate that XMAM can still complete the global model training task even when there are 40%malicious clients.Finally,we analyze our method's screening complexity and compare the real screening time with other methods.The results show that XMAM is about 10–10000 times faster than the existing methods.
基金financially supported by the Joint Funds of the National Natural Science Foundation of China(U22A20609)the National Key Research and Development Program of China(2021YFD1901102-4)+2 种基金the State Key Laboratory of Integrative Sustainable Dryland Agriculture(in preparation)the Shanxi Agricultural University,China(202003-3)the Open Fund from the State Key Laboratory of Soil Environment and Nutrient Resources of Shanxi Province,China(2020002)。
文摘Tillage practices during the fallow period benefit water storage and yield in dryland wheat crops.However,there is currently no clarity on the responses of soil organic carbon(SOC),total nitrogen(TN),and available nutrients to tillage practices within the growing season.This study evaluated the effects of three tillage practices(NT,no tillage;SS,subsoil tillage;DT,deep tillage)over five years on soil physicochemical properties.Soil samples at harvest stage from the fifth year were analyzed to determine the soil aggregate and aggregate-associated C and N fractions.The results indicated that SS and DT improved grain yield,straw biomass and straw carbon return of wheat compared with NT.In contrast to DT and NT,SS favored SOC and TN concentrations and stocks by increasing the soil organic carbon sequestration rate(SOCSR)and soil nitrogen sequestration rate(TNSR)in the 0-40 cm layer.Higher SOC levels under SS and NT were associated with greater aggregate-associated C fractions,while TN was positively associated with soluble organic nitrogen(SON).Compared with DT,the NT and SS treatments improved soil available nutrients in the 0-20 cm layer.These findings suggest that SS is an excellent practice for increasing soil carbon,nitrogen and nutrient availability in dryland wheat fields in North China.
基金supported by the National Natural Science Foundation of China,Nos.82271447,81771382the National Key Research and Development Program of China,No.2019 YFE0115900the"New 20 Terms of Universities in Jinan,No.202228022 (all to ZZ)。
文摘α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.
基金supported by the National Key R&D Program of China(Nos.2019YFD0901204,2019YFD 0901205).
文摘Aggregation of species with similar ecological properties is one of the effective methods to simplify food web researches.However,species aggregation will affect not only the complexity of modeling process but also the accuracy of models’outputs.Selection of aggregation methods and the number of trophospecies are the keys to study the simplification of food web.In this study,three aggregation methods,including taxonomic aggregation(TA),structural equivalence aggregation(SEA),and self-organizing maps(SOM),were analyzed and compared with the linear inverse model–Markov Chain Monte Carlo(LIM-MCMC)model.Impacts of aggregation methods and trophospecies number on food webs were evaluated based on the robustness and unitless of ecological net-work indices.Results showed that aggregation method of SEA performed better than the other two methods in estimating food web structure and function indices.The effects of aggregation methods were driven by the differences in species aggregation principles,which will alter food web structure and function through the redistribution of energy flow.According to the results of mean absolute percentage error(MAPE)which can be applied to evaluate the accuracy of the model,we found that MAPE in food web indices will increase with the reducing trophospecies number,and MAPE in food web function indices were smaller and more stable than those in food web structure indices.Therefore,trade-off between simplifying food webs and reflecting the status of ecosystem should be con-sidered in food web studies.These findings highlight the importance of aggregation methods and trophospecies number in the analy-sis of food web simplification.This study provided a framework to explore the extent to which food web models are affected by dif-ferent species aggregation,and will provide scientific basis for the construction of food webs.
基金Funded by the National Natural Science Foundation of China(No.U1904188)。
文摘A simplex centroid design method was employed to design the gradation of recycled coarse aggregate.The bulk density was measured while the specific surface area and average excess paste thickness were calculated with different gradations.The fluidity,dynamic yield stress,static yield stress,printed width,printed inclination,compressive strength and ultrasonic wave velocity of 3D printed recycled aggregate concrete(3DPRAC)were further studied.The experimental results demonstrate that,with the increase of small-sized aggregate(4.75-7 mm)content,the bulk density initially increases and then decreases,and the specific surface area gradually increases.The average excess paste thickness fluctuates with both bulk density and specific surface area.The workability of 3DPRAC is closely related to the average excess paste thickness.With an increase in average paste thickness,there is a gradual decrease in dynamic yield stress,static yield stress and printed inclination,accompanied by an increase in fluidity and printed width.The mechanical performance of 3DPRAC closely correlates with the bulk density.With an increase in the bulk density,there is an increase in the ultrasonic wave velocity,accompanied by a slight increase in the compressive strength and a significant decrease in the anisotropic coefficient.Furthermore,an index for buildability failure of 3DPRAC based on the average excess paste thickness is proposed.
基金partially supported by the National Key Research and Development Program of China(No.2018 AAA0100400)the Natural Science Foundation of Shandong Province(Nos.ZR2020MF131 and ZR2021ZD19)the Science and Technology Program of Qingdao(No.21-1-4-ny-19-nsh).
文摘Underwater pulse waveform recognition is an important method for underwater object detection.Most existing works focus on the application of traditional pattern recognition methods,which ignore the time-and space-varying characteristics in sound propagation channels and cannot easily extract valuable waveform features.Sound propagation channels in seawater are time-and space-varying convolutional channels.In the extraction of the waveform features of underwater acoustic signals,the effect of high-accuracy underwater acoustic signal recognition is identified by eliminating the influence of time-and space-varying convolutional channels to the greatest extent possible.We propose a hash aggregate discriminative network(HADN),which combines hash learning and deep learning to minimize the time-and space-varying effects on convolutional channels and adaptively learns effective underwater waveform features to achieve high-accuracy underwater pulse waveform recognition.In the extraction of the hash features of acoustic signals,a discrete constraint between clusters within a hash feature class is introduced.This constraint can ensure that the influence of convolutional channels on hash features is minimized.In addition,we design a new loss function called aggregate discriminative loss(AD-loss).The use of AD-loss and softmax-loss can increase the discriminativeness of the learned hash features.Experimental results show that on pool and ocean datasets,which were collected in pools and oceans,respectively,by using acoustic collectors,the proposed HADN performs better than other comparative models in terms of accuracy and mAP.
基金supported by the National Natural Science Foundation of China(22178293)the Natural Science Foundation of Fujian Province of China(2022J01022)。
文摘The bioreduction of graphene oxide(GO)using environmentally functional bacteria such as Shewanella represents a green approach to produce reduced graphene oxide(rGO).This process differs from the chemical reduction that involves instantaneous molecular reactions.In bioreduction,the contact of bacterial cells and GO is considered the rate-limiting step.To reveal how the bacteria-GO integration regulates rGO production,the comparative experiments of GO and three Shewanella strains were carried out.Fourier-transform infrared spectroscopy,X-ray photoelectron spectroscopy,Raman spectroscopy,and atomic force microscopy were used to characterize the reduction degree and the aggregation degree.The results showed that a spontaneous aggregation of GO and Shewanella into the condensed entity occurred within 36 h.A positive linear correlation was established,linking three indexes of the aggregation potential,the bacterial reduction ability,and the reduction degree(ID/IG)comprehensively.