In multimodal human computer dialog,non-verbal channels,such as facial expression,posture,gesture,etc,combined with spoken information,are also important in the procedure of dialogue.Nowadays,in spite of high performa...In multimodal human computer dialog,non-verbal channels,such as facial expression,posture,gesture,etc,combined with spoken information,are also important in the procedure of dialogue.Nowadays,in spite of high performance of users*single channel behavior computing,it is still great challenge to understand users1 intention accurately from their multimodal behaviors.One reason for this challenge is that we still need to improve multimodal information fusion in theories,methodologies and practical systems.This paper presents a review of data fusion methods in multimodal human computer dialog.We first introduce the cognitive assumption of single channel processing,and then discuss its implementation methods in human computer dialog;for the task of multi-modal information fusion,serval computing models are presented after we introduce the principle description of multiple data fusion.Finally,some practical examples of multimodal information fusion methods are introduced and the possible and important breakthroughs of the data fusion methods in future multimodal human-computer interaction applications are discussed.展开更多
With COM,VB and VC,we develop a visual human computer interaction system,which is used to mine association rules.It can mine association rules from the database which is created by Access and SQL server,as well as the...With COM,VB and VC,we develop a visual human computer interaction system,which is used to mine association rules.It can mine association rules from the database which is created by Access and SQL server,as well as the text mode.With the interaction interface,user participates in the process of data mining,making the system mine the satisfying rules.展开更多
Bio-based human computer interface (HCI) has attracted more and more attention of researches all over the world in recent years. In this paper, a HCI system which based on electrooculogram (EOG) is proposed. It transf...Bio-based human computer interface (HCI) has attracted more and more attention of researches all over the world in recent years. In this paper, a HCI system which based on electrooculogram (EOG) is proposed. It transforms electrical po-tentials recorded by horizontal and vertical EOG into a computer in order to control external equipment. The system consists of EOG acqui-sition unit, EOG pattern recognition part and control command output unit. Three plane elec-trodes are employed to detect EOG signals, which contain the information related to the eye blinking and vertical (or horizontal) eye move-ments referred to pre-designed command table. An online signal processing algorithm is de-signed to get the command information con-tained in EOG signals, and these commands could be used to control the computer or other instruments. Based on this HCI system, the remote control experiments driven by EOG are realized.展开更多
BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanis...BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.展开更多
The periphery of the Qinghai-Tibet Plateau is renowned for its susceptibility to landslides.However,the northwestern margin of this region,characterised by limited human activities and challenging transportation,remai...The periphery of the Qinghai-Tibet Plateau is renowned for its susceptibility to landslides.However,the northwestern margin of this region,characterised by limited human activities and challenging transportation,remains insufficiently explored concerning landslide occurrence and dispersion.With the planning and construction of the Xinjiang-Xizang Railway,a comprehensive investigation into disastrous landslides in this area is essential for effective disaster preparedness and mitigation strategies.By using the human-computer interaction interpretation approach,the authors established a landslide database encompassing 13003 landslides,collectively spanning an area of 3351.24 km^(2)(36°N-40°N,73°E-78°E).The database incorporates diverse topographical and environmental parameters,including regional elevation,slope angle,slope aspect,distance to faults,distance to roads,distance to rivers,annual precipitation,and stratum.The statistical characteristics of number and area of landslides,landslide number density(LND),and landslide area percentage(LAP)are analyzed.The authors found that a predominant concentration of landslide origins within high slope angle regions,with the highest incidence observed in intervals characterised by average slopes of 20°to 30°,maximum slope angle above 80°,along with orientations towards the north(N),northeast(NE),and southwest(SW).Additionally,elevations above 4.5 km,distance to rivers below 1 km,rainfall between 20-30 mm and 30-40 mm emerge as particularly susceptible to landslide development.The study area’s geological composition primarily comprises Mesozoic and Upper Paleozoic outcrops.Both fault and human engineering activities have different degrees of influence on landslide development.Furthermore,the significance of the landslide database,the relationship between landslide distribution and environmental factors,and the geometric and morphological characteristics of landslides are discussed.The landslide H/L ratios in the study area are mainly concentrated between 0.4 and 0.64.It means the landslides mobility in the region is relatively low,and the authors speculate that landslides in this region more possibly triggered by earthquakes or located in meizoseismal area.展开更多
To solve the problem of risk identification and quantitative assessment for human-computer interaction(HCI)in complex avionics systems,an HCI safety analysis framework based on system-theoretical process analysis(STPA...To solve the problem of risk identification and quantitative assessment for human-computer interaction(HCI)in complex avionics systems,an HCI safety analysis framework based on system-theoretical process analysis(STPA)and cognitive reliability and error analysis method(CREAM)is proposed.STPACREAM can identify unsafe control actions and find the causal path during the interaction of avionics systems and pilot with the help of formal verification tools automatically.The common performance conditions(CPC)of avionics systems in the aviation environment is established and a quantitative analysis of human failure is carried out.Taking the head-up display(HUD)system interaction process as an example,a case analysis is carried out,the layered safety control structure and formal model of the HUD interaction process are established.For the interactive behavior“Pilots approaching with HUD”,four unsafe control actions and35 causal scenarios are identified and the impact of common performance conditions at different levels on the pilot decision model are analyzed.The results show that HUD's HCI level gradually improves as the scores of CPC increase,and the quality of crew member cooperation and time sufficiency of the task is the key to its HCI.Through case analysis,it is shown that STPACREAM can quantitatively assess the hazards in HCI and identify the key factors that impact safety.展开更多
Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a...Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.展开更多
BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver fu...BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.展开更多
Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics ...Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,biochemistry,microbiology,immunology and toxicology.展开更多
Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics ...Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.展开更多
Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata...Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
The Internet of Things(IoT)and mobile technology have significantly transformed healthcare by enabling real-time monitoring and diagnosis of patients.Recognizing Medical-Related Human Activities(MRHA)is pivotal for he...The Internet of Things(IoT)and mobile technology have significantly transformed healthcare by enabling real-time monitoring and diagnosis of patients.Recognizing Medical-Related Human Activities(MRHA)is pivotal for healthcare systems,particularly for identifying actions critical to patient well-being.However,challenges such as high computational demands,low accuracy,and limited adaptability persist in Human Motion Recognition(HMR).While some studies have integrated HMR with IoT for real-time healthcare applications,limited research has focused on recognizing MRHA as essential for effective patient monitoring.This study proposes a novel HMR method tailored for MRHA detection,leveraging multi-stage deep learning techniques integrated with IoT.The approach employs EfficientNet to extract optimized spatial features from skeleton frame sequences using seven Mobile Inverted Bottleneck Convolutions(MBConv)blocks,followed by Convolutional Long Short Term Memory(ConvLSTM)to capture spatio-temporal patterns.A classification module with global average pooling,a fully connected layer,and a dropout layer generates the final predictions.The model is evaluated on the NTU RGB+D 120 and HMDB51 datasets,focusing on MRHA such as sneezing,falling,walking,sitting,etc.It achieves 94.85%accuracy for cross-subject evaluations and 96.45%for cross-view evaluations on NTU RGB+D 120,along with 89.22%accuracy on HMDB51.Additionally,the system integrates IoT capabilities using a Raspberry Pi and GSM module,delivering real-time alerts via Twilios SMS service to caregivers and patients.This scalable and efficient solution bridges the gap between HMR and IoT,advancing patient monitoring,improving healthcare outcomes,and reducing costs.展开更多
Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles o...Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA ...BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA treatments,their use is limited by the condition itself,and understanding of the underlying mechanisms of OA is lacking.AIM To explore the specific molecular mechanism by which hUC-MSC-derived exosomal miR-199a-3p improves OA.METHODS Sodium iodoacetate was injected into rat articulations to construct an animal model of OA.Interleukin(IL)-1βwas used to induce human chondrocytes(CHON-001)to construct an OA chondrocyte model.Exosomes in hUC-MSCs were isolated using Ribo™Exosome Isolation Reagent.Real-time reverse transcriptase-polymerase chain reaction and western blotting were used to detect the expression of related genes and proteins,and damage to CHON-001 cells and rat articular cartilage tissue was evaluated by enzyme-linked immunosorbent assay,terminal deoxynucleotidyl transferase-mediated deoxyuridine tripho-sphate-nick end labelling staining and hematoxylin and eosin staining.RESULTS hUC-MSC-derived exosomes(hUC-MSC-Exos)inhibited the expression of IL-1β-induced inflammatory cytokines,namely,IL-6,IL-8 and tumor necrosis factor-α.hUC-MSC-Exos also improved the viability but inhibited the apoptosis of CHON-001 cells,improved the pathological condition of articular cartilage tissue and alleviated the development of OA in vivo.Mechanistically,hUC-MSC-Exos downregulated the expression of mitogen-activated protein kinase 4 by delivering miR-199a-3p,thereby inhibiting the activation of the nuclear factor-kappaB signaling pathway,alleviating IL-1β-induced chondrocyte inflammation and apoptosis,and ultimately improving the development of OA.CONCLUSION hUC-MSC-derived exosomal miR-199a-3p alleviates OA by inhibiting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway.The present findings suggest that miR-199a-3p delivery by hUC-MSCExos may be a novel strategy for the treatment of OA.展开更多
Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocyt...Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.展开更多
With the development of technology and the progress of life,more and more people,regardless of entertainment,learning,or work,cannot do without computer desks and cannot put down their mobile phones.Due to prolonged s...With the development of technology and the progress of life,more and more people,regardless of entertainment,learning,or work,cannot do without computer desks and cannot put down their mobile phones.Due to prolonged sitting and often neglecting the importance of posture,incorrect posture can often lead to health problems such as hunchback,lumbar muscle strain,and shoulder and neck pain over time.To address this issue,we designed a computer vision-based human body posture detection system.The system utilizes YOLOv8 technology to accurately locate key points of the human body skeleton,and then analyzes the coordinate positions and depth information of these key points to establish a criterion for distinguishing different postures.With the assistance of an SVM classifier,the system achieves an average recognition rate of 95%.Finally,we successfully deployed the posture detection system on Raspberry Pi hardware and conducted extensive testing.The test results demonstrate that the system can effectively detect various postures and provide real-time reminders to users to correct poor posture,demonstrating good practicality and stability.展开更多
AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.展开更多
TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal...TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.展开更多
基金the National Natural Science Foundation of China(61873269,61425017,61332017,61831022)the National Key Research&Development Plan of China(2017YFB1002804).
文摘In multimodal human computer dialog,non-verbal channels,such as facial expression,posture,gesture,etc,combined with spoken information,are also important in the procedure of dialogue.Nowadays,in spite of high performance of users*single channel behavior computing,it is still great challenge to understand users1 intention accurately from their multimodal behaviors.One reason for this challenge is that we still need to improve multimodal information fusion in theories,methodologies and practical systems.This paper presents a review of data fusion methods in multimodal human computer dialog.We first introduce the cognitive assumption of single channel processing,and then discuss its implementation methods in human computer dialog;for the task of multi-modal information fusion,serval computing models are presented after we introduce the principle description of multiple data fusion.Finally,some practical examples of multimodal information fusion methods are introduced and the possible and important breakthroughs of the data fusion methods in future multimodal human-computer interaction applications are discussed.
文摘With COM,VB and VC,we develop a visual human computer interaction system,which is used to mine association rules.It can mine association rules from the database which is created by Access and SQL server,as well as the text mode.With the interaction interface,user participates in the process of data mining,making the system mine the satisfying rules.
文摘Bio-based human computer interface (HCI) has attracted more and more attention of researches all over the world in recent years. In this paper, a HCI system which based on electrooculogram (EOG) is proposed. It transforms electrical po-tentials recorded by horizontal and vertical EOG into a computer in order to control external equipment. The system consists of EOG acqui-sition unit, EOG pattern recognition part and control command output unit. Three plane elec-trodes are employed to detect EOG signals, which contain the information related to the eye blinking and vertical (or horizontal) eye move-ments referred to pre-designed command table. An online signal processing algorithm is de-signed to get the command information con-tained in EOG signals, and these commands could be used to control the computer or other instruments. Based on this HCI system, the remote control experiments driven by EOG are realized.
基金Supported by the National Research Foundation of Korea,No.2020R1A2C1100891Soonchunhyang University Research Fund,No.2024-05-014.
文摘BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.
基金supported by the National Key Research and Development Program of China(2021YFB3901205)National Institute of Natural Hazards,Ministry of Emergency Management of China(2023-JBKY-57)。
文摘The periphery of the Qinghai-Tibet Plateau is renowned for its susceptibility to landslides.However,the northwestern margin of this region,characterised by limited human activities and challenging transportation,remains insufficiently explored concerning landslide occurrence and dispersion.With the planning and construction of the Xinjiang-Xizang Railway,a comprehensive investigation into disastrous landslides in this area is essential for effective disaster preparedness and mitigation strategies.By using the human-computer interaction interpretation approach,the authors established a landslide database encompassing 13003 landslides,collectively spanning an area of 3351.24 km^(2)(36°N-40°N,73°E-78°E).The database incorporates diverse topographical and environmental parameters,including regional elevation,slope angle,slope aspect,distance to faults,distance to roads,distance to rivers,annual precipitation,and stratum.The statistical characteristics of number and area of landslides,landslide number density(LND),and landslide area percentage(LAP)are analyzed.The authors found that a predominant concentration of landslide origins within high slope angle regions,with the highest incidence observed in intervals characterised by average slopes of 20°to 30°,maximum slope angle above 80°,along with orientations towards the north(N),northeast(NE),and southwest(SW).Additionally,elevations above 4.5 km,distance to rivers below 1 km,rainfall between 20-30 mm and 30-40 mm emerge as particularly susceptible to landslide development.The study area’s geological composition primarily comprises Mesozoic and Upper Paleozoic outcrops.Both fault and human engineering activities have different degrees of influence on landslide development.Furthermore,the significance of the landslide database,the relationship between landslide distribution and environmental factors,and the geometric and morphological characteristics of landslides are discussed.The landslide H/L ratios in the study area are mainly concentrated between 0.4 and 0.64.It means the landslides mobility in the region is relatively low,and the authors speculate that landslides in this region more possibly triggered by earthquakes or located in meizoseismal area.
基金supported by the National Key Research and Development Program of China(2021YFB1600601)the Joint Funds of the National Natural Science Foundation of China and the Civil Aviation Administration of China(U1933106)+2 种基金the Scientific Research Project of Tianjin Educational Committee(2019KJ134)the Natural Science Foundation of TianjinIntelligent Civil Aviation Program(21JCQNJ C00900)。
文摘To solve the problem of risk identification and quantitative assessment for human-computer interaction(HCI)in complex avionics systems,an HCI safety analysis framework based on system-theoretical process analysis(STPA)and cognitive reliability and error analysis method(CREAM)is proposed.STPACREAM can identify unsafe control actions and find the causal path during the interaction of avionics systems and pilot with the help of formal verification tools automatically.The common performance conditions(CPC)of avionics systems in the aviation environment is established and a quantitative analysis of human failure is carried out.Taking the head-up display(HUD)system interaction process as an example,a case analysis is carried out,the layered safety control structure and formal model of the HUD interaction process are established.For the interactive behavior“Pilots approaching with HUD”,four unsafe control actions and35 causal scenarios are identified and the impact of common performance conditions at different levels on the pilot decision model are analyzed.The results show that HUD's HCI level gradually improves as the scores of CPC increase,and the quality of crew member cooperation and time sufficiency of the task is the key to its HCI.Through case analysis,it is shown that STPACREAM can quantitatively assess the hazards in HCI and identify the key factors that impact safety.
基金supported by the National Natural Science Foundation of China(32171347)the Foundation of Leading Talents from Shanghai Health Commission(2022XD038)+1 种基金Training Program for Research Physicians in Innovation,the Funda-mental Research Funds for the Central Universities(YG2023QNA23)Transforma-tion from shanghai hospital development center(SHDC2022CRD002).
文摘Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
文摘BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.
文摘Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,biochemistry,microbiology,immunology and toxicology.
文摘Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.
文摘Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
基金funded by the ICT Division of theMinistry of Posts,Telecommunications,and Information Technology of Bangladesh under Grant Number 56.00.0000.052.33.005.21-7(Tracking No.22FS15306)support from the University of Rajshahi.
文摘The Internet of Things(IoT)and mobile technology have significantly transformed healthcare by enabling real-time monitoring and diagnosis of patients.Recognizing Medical-Related Human Activities(MRHA)is pivotal for healthcare systems,particularly for identifying actions critical to patient well-being.However,challenges such as high computational demands,low accuracy,and limited adaptability persist in Human Motion Recognition(HMR).While some studies have integrated HMR with IoT for real-time healthcare applications,limited research has focused on recognizing MRHA as essential for effective patient monitoring.This study proposes a novel HMR method tailored for MRHA detection,leveraging multi-stage deep learning techniques integrated with IoT.The approach employs EfficientNet to extract optimized spatial features from skeleton frame sequences using seven Mobile Inverted Bottleneck Convolutions(MBConv)blocks,followed by Convolutional Long Short Term Memory(ConvLSTM)to capture spatio-temporal patterns.A classification module with global average pooling,a fully connected layer,and a dropout layer generates the final predictions.The model is evaluated on the NTU RGB+D 120 and HMDB51 datasets,focusing on MRHA such as sneezing,falling,walking,sitting,etc.It achieves 94.85%accuracy for cross-subject evaluations and 96.45%for cross-view evaluations on NTU RGB+D 120,along with 89.22%accuracy on HMDB51.Additionally,the system integrates IoT capabilities using a Raspberry Pi and GSM module,delivering real-time alerts via Twilios SMS service to caregivers and patients.This scalable and efficient solution bridges the gap between HMR and IoT,advancing patient monitoring,improving healthcare outcomes,and reducing costs.
基金supported by the National Natural Science Foundation of China(Nos.22206207,22127810,and 22276224)the Natural Science Foundation of Guangdong Province(Nos.2021A1515011546 and 2023A1515010085)the Science and Technology Planning Project of Guangzhou(No.202102080005)。
文摘Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金Supported by Basic Research Plan of Yunnan Province,No.202201AT070059National Natural Science Foundation of China,No.81760407Science and Technology Talent and Platform Plan of Yunnan Provincial Department of Science and Technology,No.202205AC160066.
文摘BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA treatments,their use is limited by the condition itself,and understanding of the underlying mechanisms of OA is lacking.AIM To explore the specific molecular mechanism by which hUC-MSC-derived exosomal miR-199a-3p improves OA.METHODS Sodium iodoacetate was injected into rat articulations to construct an animal model of OA.Interleukin(IL)-1βwas used to induce human chondrocytes(CHON-001)to construct an OA chondrocyte model.Exosomes in hUC-MSCs were isolated using Ribo™Exosome Isolation Reagent.Real-time reverse transcriptase-polymerase chain reaction and western blotting were used to detect the expression of related genes and proteins,and damage to CHON-001 cells and rat articular cartilage tissue was evaluated by enzyme-linked immunosorbent assay,terminal deoxynucleotidyl transferase-mediated deoxyuridine tripho-sphate-nick end labelling staining and hematoxylin and eosin staining.RESULTS hUC-MSC-derived exosomes(hUC-MSC-Exos)inhibited the expression of IL-1β-induced inflammatory cytokines,namely,IL-6,IL-8 and tumor necrosis factor-α.hUC-MSC-Exos also improved the viability but inhibited the apoptosis of CHON-001 cells,improved the pathological condition of articular cartilage tissue and alleviated the development of OA in vivo.Mechanistically,hUC-MSC-Exos downregulated the expression of mitogen-activated protein kinase 4 by delivering miR-199a-3p,thereby inhibiting the activation of the nuclear factor-kappaB signaling pathway,alleviating IL-1β-induced chondrocyte inflammation and apoptosis,and ultimately improving the development of OA.CONCLUSION hUC-MSC-derived exosomal miR-199a-3p alleviates OA by inhibiting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway.The present findings suggest that miR-199a-3p delivery by hUC-MSCExos may be a novel strategy for the treatment of OA.
基金supported by the National Natural Science Foundation of China,No.82301403(to DZ)。
文摘Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.
基金funded by the Science and Technology Project of Hebei Education Department (No.ZD2022100).
文摘With the development of technology and the progress of life,more and more people,regardless of entertainment,learning,or work,cannot do without computer desks and cannot put down their mobile phones.Due to prolonged sitting and often neglecting the importance of posture,incorrect posture can often lead to health problems such as hunchback,lumbar muscle strain,and shoulder and neck pain over time.To address this issue,we designed a computer vision-based human body posture detection system.The system utilizes YOLOv8 technology to accurately locate key points of the human body skeleton,and then analyzes the coordinate positions and depth information of these key points to establish a criterion for distinguishing different postures.With the assistance of an SVM classifier,the system achieves an average recognition rate of 95%.Finally,we successfully deployed the posture detection system on Raspberry Pi hardware and conducted extensive testing.The test results demonstrate that the system can effectively detect various postures and provide real-time reminders to users to correct poor posture,demonstrating good practicality and stability.
基金Supported by grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
基金supported by the Koeln Fortune Program/Faculty of Medicine,University of Cologne,the Alzheimer Forschung Initiative e.V.(grant#22039,to HZ)open-access funding from the DFG/GRC issued to the University of CologneAlzheimer Forschung Initiative e.V.for Open Access Publishing(a publication grant#P2401,to MAAK)。
文摘TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.
