The FitzHugh–Nagumo neuron circuit integrates a piezoelectric ceramic to form a piezoelectric sensing neuron,which can capture external sound signals and simulate the auditory neuron system.Two piezoelectric sensing ...The FitzHugh–Nagumo neuron circuit integrates a piezoelectric ceramic to form a piezoelectric sensing neuron,which can capture external sound signals and simulate the auditory neuron system.Two piezoelectric sensing neurons are coupled by a parallel circuit consisting of a Josephson junction and a linear resistor,and a binaural auditory system is established.Considering the non-singleness of external sound sources,the high–low frequency signal is used as the input signal to study the firing mode transition and synchronization of this system.It is found that the angular frequency of the high–low frequency signal is a key factor in determining whether the dynamic behaviors of two coupled neurons are synchronous.When they are in synchronization at a specific angular frequency,the changes in physical parameters of the input signal and the coupling strength between them will not destroy their synchronization.In addition,the firing mode of two coupled auditory neurons in synchronization is affected by the characteristic parameters of the high–low frequency signal rather than the coupling strength.The asynchronous dynamic behavior and variations in firing modes will harm the auditory system.These findings could help determine the causes of hearing loss and devise functional assistive devices for patients.展开更多
In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking ...In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.展开更多
Background: Plastic pollution is the accumulation of waste composed of plastic and its derivatives all over the environment. Whether in the form of visible garbage or microparticles, as it slowly degrades, plastic pol...Background: Plastic pollution is the accumulation of waste composed of plastic and its derivatives all over the environment. Whether in the form of visible garbage or microparticles, as it slowly degrades, plastic pollution poses significant threats to terrestrial and aquatic habitats and the wildlife that call them home, whether through ingestion, entanglement or exposure to the chemicals contained in the material. Unfortunately, there is a lack of documentation on the impact of plastic waste on human health in low- and middle-income countries (LMICs). Methods: We searched five electronic databases (PubMed, Embase, Global Health, CINAHL and Web of Science) and gray literature, following the preferred reporting elements for systematic reviews and meta-analyses (PRISMA), for the impact of plastic waste on human health in developing countries. We included quantitative and qualitative studies written in English and French. We assessed the quality of the included articles using the Mixed Methods Appraisal tool (MMAT). Results: A total of 3779 articles were initially identified by searching electronic databases. After eliminating duplicates, 3167 articles were reviewed based on title and abstract, and 26 were selected for full-text review. Only three articles were retained. The three articles dealt with practices likely to lead to oral exposure to plastic chemicals in human health, as well as the level of awareness of participants concerning the possible impact of plastic on human health, namely, the use of plastic baby bottles, the use of microwaves to cook food and reheat precooked food, the use of plastic bottles to store water in the refrigerator, water purifier containers with plastic bodies and plastic lunch boxes, the reuse of plastic bags and the inadequacy of treatment facilities. Conclusion: Plastic waste poses different risks to human health at every stage of its life cycle. Hence, strategies must be adopted to raise public awareness of the dangers of plastic waste to their health. Trial registration: The review protocol is registered in the PROSPERO international prospective register of systematic reviews (ID = CRD42023409087).展开更多
Context/objectives: The fight against Chronic Non-Communicable Diseases (NCDs) is a long-term undertaking, which requires available, motivated and well-managed human resources (HR). The administrative management of sk...Context/objectives: The fight against Chronic Non-Communicable Diseases (NCDs) is a long-term undertaking, which requires available, motivated and well-managed human resources (HR). The administrative management of skills on both qualitative and quantitative levels is one of the essential functions of a health system. To better implement policies of fight against High Blood Pressure (HBP) and other chronic diseases, it is important to establish strategies to retain health personnel. This loyalty requires favorable working conditions and consideration of the contribution-reward couple. Good working conditions are likely to reduce the phenomenon of medical nomadism;conversely, poor HR management can contribute to their exodus towards exotic “green pastures”, thus leading to an additional crisis in the Cameroonian health system. The fight against HBP is a complex, multifaceted and multifactorial reality that requires appropriate management model for all types of resources mainly HR. The main objective of this research is to show the impact of poor management of human resources in Cameroon health system on medical nomadism and the ineffectiveness of the fight against High Blood Pressure. Method: A cross-sectional descriptive survey among five hundred (500) health facilities in the center region of Cameroon has been conducted. A stratified probabilistic technique has been used, and the number of health facilities to be surveyed has been determined using the “sample size estimation table” of Depelteau. The physical questionnaires have been printed and then distributed to data collectors. After data collection, the latter were grouped during processing in Excel sheets. The Chi-square test was used for data with a qualitative value and that of Kolmogorov-Sminorf for data with a quantitative value to assess the normality and reliability of data. The Crochach’s Alpha reliability test allowed us to have a summary of the means and variances and then to search for intragroup correlations between variables. Descriptive analysis was possible with the XLSTAT 2016 software. Results: 43.60% of Health Facilities (HF) managers were unqualified. 82.20% of HF managers have staff in a situation of professional insecurity. They are mainly contractual (49.00), decision-making agents (24.40%), casual agents (08.80). The proportion of unstable personnel is average of 22.00% and very unstable, 12.00%.展开更多
The three core issues in the“digital human rights”debate are whether“digital human rights”are possible,necessary,and feasible.Both sides of the debate focus on discovering the value of“digital human rights”to in...The three core issues in the“digital human rights”debate are whether“digital human rights”are possible,necessary,and feasible.Both sides of the debate focus on discovering the value of“digital human rights”to individuals from a semantic level,but ignore the significance of“digital human rights”to the whole society and its subsystems at the level of social structure.By introducing Niklas Luhmann's System Theory,this observation blind spot can be eliminated.Fundamental rights are devoted to directly shaping not a physiological-psychological“individual”as a social environment but a social“person”that can be included by social systems.It is clear that digital human rights are the right to participate in digital communication of a“human”as a“person”,so they are possible in terms of conceptual definition.Digital human rights can help“people”lower the threshold for participation in digital communication,limit the excessive expansion of social systems,and promote the free and complete expression of body and mind,so they are necessary for social functions.There are limitations in the existing two ideas of“incorporating digital human rights into the constitution”.Based on the new construction idea of System Theory of Law,digital human rights as the right to participate in digital communication can be typified into digital communication in social sub-fields such as politics,economy,science,and art.The right to participate constructs a complete digital human rights system,making it feasible on the basis of the constitution.展开更多
Recognizing human activity(HAR)from data in a smartphone sensor plays an important role in the field of health to prevent chronic diseases.Daily and weekly physical activities are recorded on the smartphone and tell t...Recognizing human activity(HAR)from data in a smartphone sensor plays an important role in the field of health to prevent chronic diseases.Daily and weekly physical activities are recorded on the smartphone and tell the user whether he is moving well or not.Typically,smartphones and their associated sensing devices operate in distributed and unstable environments.Therefore,collecting their data and extracting useful information is a significant challenge.In this context,the aimof this paper is twofold:The first is to analyze human behavior based on the recognition of physical activities.Using the results of physical activity detection and classification,the second part aims to develop a health recommendation system to notify smartphone users about their healthy physical behavior related to their physical activities.This system is based on the calculation of calories burned by each user during physical activities.In this way,conclusions can be drawn about a person’s physical behavior by estimating the number of calories burned after evaluating data collected daily or even weekly following a series of physical workouts.To identify and classify human behavior our methodology is based on artificial intelligence models specifically deep learning techniques like Long Short-Term Memory(LSTM),stacked LSTM,and bidirectional LSTM.Since human activity data contains both spatial and temporal information,we proposed,in this paper,to use of an architecture allowing the extraction of the two types of information simultaneously.While Convolutional Neural Networks(CNN)has an architecture designed for spatial information,our idea is to combine CNN with LSTM to increase classification accuracy by taking into consideration the extraction of both spatial and temporal data.The results obtained achieved an accuracy of 96%.On the other side,the data learned by these algorithms is prone to error and uncertainty.To overcome this constraint and improve performance(96%),we proposed to use the fusion mechanisms.The last combines deep learning classifiers tomodel non-accurate and ambiguous data to obtain synthetic information to aid in decision-making.The Voting and Dempster-Shafer(DS)approaches are employed.The results showed that fused classifiers based on DS theory outperformed individual classifiers(96%)with the highest accuracy level of 98%.Also,the findings disclosed that participants engaging in physical activities are healthy,showcasing a disparity in the distribution of physical activities between men and women.展开更多
Centering on the systematic construction of human rights theories,Xi Jinping’s discourses on respecting and protecting human rights creatively put forward a series of original theoretical viewpoints and academic prop...Centering on the systematic construction of human rights theories,Xi Jinping’s discourses on respecting and protecting human rights creatively put forward a series of original theoretical viewpoints and academic propositions,profoundly revealing the basic connotation of a contemporary Chinese outlook on human rights and realizing all-around and deep-level innovation in the construction of a contemporary human rights theoretical system.In ontology,the four-in-one view of human rights of the political party,the govern-ment,society,and the people goes beyond the dichotomy between the political state and civil society.In element theory,the substantive view of human rights surpasses the formalist view of human rights.In category theory,the view of human rights focusing on the right to sub-sistence and the right to development transcends the view of human rights based on the individual’s right to freedom.In operation theory,the“development-based human rights path”goes beyond the“hu-man rights-based development path.”In practice,the positive view of human rights based on the rule of law surpasses the negative view of human rights based on the rule of law.展开更多
Background Intelligent garments,a burgeoning class of wearable devices,have extensive applications in domains such as sports training and medical rehabilitation.Nonetheless,existing research in the smart wearables dom...Background Intelligent garments,a burgeoning class of wearable devices,have extensive applications in domains such as sports training and medical rehabilitation.Nonetheless,existing research in the smart wearables domain predominantly emphasizes sensor functionality and quantity,often skipping crucial aspects related to user experience and interaction.Methods To address this gap,this study introduces a novel real-time 3D interactive system based on intelligent garments.The system utilizes lightweight sensor modules to collect human motion data and introduces a dual-stream fusion network based on pulsed neural units to classify and recognize human movements,thereby achieving real-time interaction between users and sensors.Additionally,the system incorporates 3D human visualization functionality,which visualizes sensor data and recognizes human actions as 3D models in real time,providing accurate and comprehensive visual feedback to help users better understand and analyze the details and features of human motion.This system has significant potential for applications in motion detection,medical monitoring,virtual reality,and other fields.The accurate classification of human actions contributes to the development of personalized training plans and injury prevention strategies.Conclusions This study has substantial implications in the domains of intelligent garments,human motion monitoring,and digital twin visualization.The advancement of this system is expected to propel the progress of wearable technology and foster a deeper comprehension of human motion.展开更多
The challenge of transitioning from temporary humanitarian settlements to more sustainable human settlements is due to a significant increase in the number of forcibly displaced people over recent decades, difficultie...The challenge of transitioning from temporary humanitarian settlements to more sustainable human settlements is due to a significant increase in the number of forcibly displaced people over recent decades, difficulties in providing social services that meet the required standards, and the prolongation of emergencies. Despite this challenging context, short-term considerations continue to guide their planning and management rather than more integrated, longer-term perspectives, thus preventing viable, sustainable development. Over the years, the design of humanitarian settlements has not been adapted to local contexts and perspectives, nor to the dynamics of urbanization and population growth and data. In addition, the current approach to temporary settlement harms the environment and can strain limited resources. Inefficient land use and ad hoc development models have compounded difficulties and generated new challenges. As a result, living conditions in settlements have deteriorated over the last few decades and continue to pose new challenges. The stakes are such that major shortcomings have emerged along the way, leading to disruption, budget overruns in a context marked by a steady decline in funding. However, some attempts have been made to shift towards more sustainable approaches, but these have mainly focused on vague, sector-oriented themes, failing to consider systematic and integration views. This study is a contribution in addressing these shortcomings by designing a model-driving solution, emphasizing an integrated system conceptualized as a system of systems. This paper proposes a new methodology for designing an integrated and sustainable human settlement model, based on Model-Based Systems Engineering and a Systems Modeling Language to provide valuable insights toward sustainable solutions for displaced populations aligning with the United Nations 2030 agenda for sustainable development.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.
Due to the dynamic stiffness characteristics of human joints, it is easy to cause impact and disturbance on normal movements during exoskeleton assistance. This not only brings strict requirements for exoskeleton cont...Due to the dynamic stiffness characteristics of human joints, it is easy to cause impact and disturbance on normal movements during exoskeleton assistance. This not only brings strict requirements for exoskeleton control design, but also makes it difficult to improve assistive level. The Variable Stiffness Actuator (VSA), as a physical variable stiffness mechanism, has the characteristics of dynamic stiffness adjustment and high stiffness control bandwidth, which is in line with the stiffness matching experiment. However, there are still few works exploring the assistive human stiffness matching experiment based on VSA. Therefore, this paper designs a hip exoskeleton based on VSA actuator and studies CPG human motion phase recognition algorithm. Firstly, this paper puts forward the requirements of variable stiffness experimental design and the output torque and variable stiffness dynamic response standards based on human lower limb motion parameters. Plate springs are used as elastic elements to establish the mechanical principle of variable stiffness, and a small variable stiffness actuator is designed based on the plate spring. Then the corresponding theoretical dynamic model is established and analyzed. Starting from the CPG phase recognition algorithm, this paper uses perturbation theory to expand the first-order CPG unit, obtains the phase convergence equation and verifies the phase convergence when using hip joint angle as the input signal with the same frequency, and then expands the second-order CPG unit under the premise of circular limit cycle and analyzes the frequency convergence criterion. Afterwards, this paper extracts the plate spring modal from Abaqus and generates the neutral file of the flexible body model to import into Adams, and conducts torque-stiffness one-way loading and reciprocating loading experiments on the variable stiffness mechanism. After that, Simulink is used to verify the validity of the criterion. Finally, based on the above criterions, the signal mean value is removed using feedback structure to complete the phase recognition algorithm for the human hip joint angle signal, and the convergence is verified using actual human walking data on flat ground.展开更多
Xi Jinping’s discourses on respecting and protect-ing human rights stand as a shining example of the sinicization and modernization of Marxist human rights theory,embodying profound theoretical,political,practical,an...Xi Jinping’s discourses on respecting and protect-ing human rights stand as a shining example of the sinicization and modernization of Marxist human rights theory,embodying profound theoretical,political,practical,and cultural logic.Existing research has conducted comprehensive and systematic theoretical analysis and academic extractions on the following contents:the core essence in-herent in these important discourses,including the“theory of human rights concepts,”the“theory of human rights paths,”the“theory of human rights practices,”the“theory of human rights protection,”and the“theory of human rights governance,”along with their profound theoretical significance,practical significance,and global signifi-cance.In the future,researchers should emphasize efforts on studying the original texts and understanding the original principles.While focusing on the precision of concepts,the scientific nature of the prop-ositions,the maturity of theoretical systems,and the rigor of internal logic related to Xi Jinping’s discourses on respecting and protecting human rights,researchers should also pay attention to constructing a discourse system on human rights from the dimensions of discourse power,discourse cluster,and discourse field.Researchers should be adept at drawing innovative insights into human rights theory from China’s vibrant human rights practices and the vast masses of people.This approach will facilitate the systematic unfolding,academic trans-formation,and innovative development of Xi Jinping’s discourses on respecting and protecting human rights.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
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
In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in ped...In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.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
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
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
Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with t...Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.11605014)。
文摘The FitzHugh–Nagumo neuron circuit integrates a piezoelectric ceramic to form a piezoelectric sensing neuron,which can capture external sound signals and simulate the auditory neuron system.Two piezoelectric sensing neurons are coupled by a parallel circuit consisting of a Josephson junction and a linear resistor,and a binaural auditory system is established.Considering the non-singleness of external sound sources,the high–low frequency signal is used as the input signal to study the firing mode transition and synchronization of this system.It is found that the angular frequency of the high–low frequency signal is a key factor in determining whether the dynamic behaviors of two coupled neurons are synchronous.When they are in synchronization at a specific angular frequency,the changes in physical parameters of the input signal and the coupling strength between them will not destroy their synchronization.In addition,the firing mode of two coupled auditory neurons in synchronization is affected by the characteristic parameters of the high–low frequency signal rather than the coupling strength.The asynchronous dynamic behavior and variations in firing modes will harm the auditory system.These findings could help determine the causes of hearing loss and devise functional assistive devices for patients.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035National Key Research and Development Project,Grant/Award Number:2022YFA1103803。
文摘In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.
文摘Background: Plastic pollution is the accumulation of waste composed of plastic and its derivatives all over the environment. Whether in the form of visible garbage or microparticles, as it slowly degrades, plastic pollution poses significant threats to terrestrial and aquatic habitats and the wildlife that call them home, whether through ingestion, entanglement or exposure to the chemicals contained in the material. Unfortunately, there is a lack of documentation on the impact of plastic waste on human health in low- and middle-income countries (LMICs). Methods: We searched five electronic databases (PubMed, Embase, Global Health, CINAHL and Web of Science) and gray literature, following the preferred reporting elements for systematic reviews and meta-analyses (PRISMA), for the impact of plastic waste on human health in developing countries. We included quantitative and qualitative studies written in English and French. We assessed the quality of the included articles using the Mixed Methods Appraisal tool (MMAT). Results: A total of 3779 articles were initially identified by searching electronic databases. After eliminating duplicates, 3167 articles were reviewed based on title and abstract, and 26 were selected for full-text review. Only three articles were retained. The three articles dealt with practices likely to lead to oral exposure to plastic chemicals in human health, as well as the level of awareness of participants concerning the possible impact of plastic on human health, namely, the use of plastic baby bottles, the use of microwaves to cook food and reheat precooked food, the use of plastic bottles to store water in the refrigerator, water purifier containers with plastic bodies and plastic lunch boxes, the reuse of plastic bags and the inadequacy of treatment facilities. Conclusion: Plastic waste poses different risks to human health at every stage of its life cycle. Hence, strategies must be adopted to raise public awareness of the dangers of plastic waste to their health. Trial registration: The review protocol is registered in the PROSPERO international prospective register of systematic reviews (ID = CRD42023409087).
文摘Context/objectives: The fight against Chronic Non-Communicable Diseases (NCDs) is a long-term undertaking, which requires available, motivated and well-managed human resources (HR). The administrative management of skills on both qualitative and quantitative levels is one of the essential functions of a health system. To better implement policies of fight against High Blood Pressure (HBP) and other chronic diseases, it is important to establish strategies to retain health personnel. This loyalty requires favorable working conditions and consideration of the contribution-reward couple. Good working conditions are likely to reduce the phenomenon of medical nomadism;conversely, poor HR management can contribute to their exodus towards exotic “green pastures”, thus leading to an additional crisis in the Cameroonian health system. The fight against HBP is a complex, multifaceted and multifactorial reality that requires appropriate management model for all types of resources mainly HR. The main objective of this research is to show the impact of poor management of human resources in Cameroon health system on medical nomadism and the ineffectiveness of the fight against High Blood Pressure. Method: A cross-sectional descriptive survey among five hundred (500) health facilities in the center region of Cameroon has been conducted. A stratified probabilistic technique has been used, and the number of health facilities to be surveyed has been determined using the “sample size estimation table” of Depelteau. The physical questionnaires have been printed and then distributed to data collectors. After data collection, the latter were grouped during processing in Excel sheets. The Chi-square test was used for data with a qualitative value and that of Kolmogorov-Sminorf for data with a quantitative value to assess the normality and reliability of data. The Crochach’s Alpha reliability test allowed us to have a summary of the means and variances and then to search for intragroup correlations between variables. Descriptive analysis was possible with the XLSTAT 2016 software. Results: 43.60% of Health Facilities (HF) managers were unqualified. 82.20% of HF managers have staff in a situation of professional insecurity. They are mainly contractual (49.00), decision-making agents (24.40%), casual agents (08.80). The proportion of unstable personnel is average of 22.00% and very unstable, 12.00%.
基金a phased achievement of the research project“Research on the Basic Issues of Digital Rule of Law from the Perspective of System Theory”(Project Approval Number 22AZD149)。
文摘The three core issues in the“digital human rights”debate are whether“digital human rights”are possible,necessary,and feasible.Both sides of the debate focus on discovering the value of“digital human rights”to individuals from a semantic level,but ignore the significance of“digital human rights”to the whole society and its subsystems at the level of social structure.By introducing Niklas Luhmann's System Theory,this observation blind spot can be eliminated.Fundamental rights are devoted to directly shaping not a physiological-psychological“individual”as a social environment but a social“person”that can be included by social systems.It is clear that digital human rights are the right to participate in digital communication of a“human”as a“person”,so they are possible in terms of conceptual definition.Digital human rights can help“people”lower the threshold for participation in digital communication,limit the excessive expansion of social systems,and promote the free and complete expression of body and mind,so they are necessary for social functions.There are limitations in the existing two ideas of“incorporating digital human rights into the constitution”.Based on the new construction idea of System Theory of Law,digital human rights as the right to participate in digital communication can be typified into digital communication in social sub-fields such as politics,economy,science,and art.The right to participate constructs a complete digital human rights system,making it feasible on the basis of the constitution.
基金the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia for funding this research work through the Project Number 223202.
文摘Recognizing human activity(HAR)from data in a smartphone sensor plays an important role in the field of health to prevent chronic diseases.Daily and weekly physical activities are recorded on the smartphone and tell the user whether he is moving well or not.Typically,smartphones and their associated sensing devices operate in distributed and unstable environments.Therefore,collecting their data and extracting useful information is a significant challenge.In this context,the aimof this paper is twofold:The first is to analyze human behavior based on the recognition of physical activities.Using the results of physical activity detection and classification,the second part aims to develop a health recommendation system to notify smartphone users about their healthy physical behavior related to their physical activities.This system is based on the calculation of calories burned by each user during physical activities.In this way,conclusions can be drawn about a person’s physical behavior by estimating the number of calories burned after evaluating data collected daily or even weekly following a series of physical workouts.To identify and classify human behavior our methodology is based on artificial intelligence models specifically deep learning techniques like Long Short-Term Memory(LSTM),stacked LSTM,and bidirectional LSTM.Since human activity data contains both spatial and temporal information,we proposed,in this paper,to use of an architecture allowing the extraction of the two types of information simultaneously.While Convolutional Neural Networks(CNN)has an architecture designed for spatial information,our idea is to combine CNN with LSTM to increase classification accuracy by taking into consideration the extraction of both spatial and temporal data.The results obtained achieved an accuracy of 96%.On the other side,the data learned by these algorithms is prone to error and uncertainty.To overcome this constraint and improve performance(96%),we proposed to use the fusion mechanisms.The last combines deep learning classifiers tomodel non-accurate and ambiguous data to obtain synthetic information to aid in decision-making.The Voting and Dempster-Shafer(DS)approaches are employed.The results showed that fused classifiers based on DS theory outperformed individual classifiers(96%)with the highest accuracy level of 98%.Also,the findings disclosed that participants engaging in physical activities are healthy,showcasing a disparity in the distribution of physical activities between men and women.
基金the“Research on the Practice of Contin-uous Building the System of Socialist Rule of Law with Chinese Characteristics and Advancing Law-based Governance,”a major special project of philosophy and social sciences research of the Ministry of Education(Project Number 2022JZDZ002).
文摘Centering on the systematic construction of human rights theories,Xi Jinping’s discourses on respecting and protecting human rights creatively put forward a series of original theoretical viewpoints and academic propositions,profoundly revealing the basic connotation of a contemporary Chinese outlook on human rights and realizing all-around and deep-level innovation in the construction of a contemporary human rights theoretical system.In ontology,the four-in-one view of human rights of the political party,the govern-ment,society,and the people goes beyond the dichotomy between the political state and civil society.In element theory,the substantive view of human rights surpasses the formalist view of human rights.In category theory,the view of human rights focusing on the right to sub-sistence and the right to development transcends the view of human rights based on the individual’s right to freedom.In operation theory,the“development-based human rights path”goes beyond the“hu-man rights-based development path.”In practice,the positive view of human rights based on the rule of law surpasses the negative view of human rights based on the rule of law.
基金Supported by the National Natural Science Foundation of China (62202346)Hubei Key Research and Development Program (2021BAA042)+3 种基金Open project of Engineering Research Center of Hubei Province for Clothing Information (2022HBCI01)Wuhan Applied Basic Frontier Research Project (2022013988065212)MIIT′s AI Industry Innovation Task Unveils Flagship Projects (Key Technologies,Equipment,and Systems for Flexible Customized and Intelligent Manufacturing in the Clothing Industry)Hubei Science and Technology Project of Safe Production Special Fund (Scene Control Platform Based on Proprioception Information Computing of Artificial Intelligence)。
文摘Background Intelligent garments,a burgeoning class of wearable devices,have extensive applications in domains such as sports training and medical rehabilitation.Nonetheless,existing research in the smart wearables domain predominantly emphasizes sensor functionality and quantity,often skipping crucial aspects related to user experience and interaction.Methods To address this gap,this study introduces a novel real-time 3D interactive system based on intelligent garments.The system utilizes lightweight sensor modules to collect human motion data and introduces a dual-stream fusion network based on pulsed neural units to classify and recognize human movements,thereby achieving real-time interaction between users and sensors.Additionally,the system incorporates 3D human visualization functionality,which visualizes sensor data and recognizes human actions as 3D models in real time,providing accurate and comprehensive visual feedback to help users better understand and analyze the details and features of human motion.This system has significant potential for applications in motion detection,medical monitoring,virtual reality,and other fields.The accurate classification of human actions contributes to the development of personalized training plans and injury prevention strategies.Conclusions This study has substantial implications in the domains of intelligent garments,human motion monitoring,and digital twin visualization.The advancement of this system is expected to propel the progress of wearable technology and foster a deeper comprehension of human motion.
文摘The challenge of transitioning from temporary humanitarian settlements to more sustainable human settlements is due to a significant increase in the number of forcibly displaced people over recent decades, difficulties in providing social services that meet the required standards, and the prolongation of emergencies. Despite this challenging context, short-term considerations continue to guide their planning and management rather than more integrated, longer-term perspectives, thus preventing viable, sustainable development. Over the years, the design of humanitarian settlements has not been adapted to local contexts and perspectives, nor to the dynamics of urbanization and population growth and data. In addition, the current approach to temporary settlement harms the environment and can strain limited resources. Inefficient land use and ad hoc development models have compounded difficulties and generated new challenges. As a result, living conditions in settlements have deteriorated over the last few decades and continue to pose new challenges. The stakes are such that major shortcomings have emerged along the way, leading to disruption, budget overruns in a context marked by a steady decline in funding. However, some attempts have been made to shift towards more sustainable approaches, but these have mainly focused on vague, sector-oriented themes, failing to consider systematic and integration views. This study is a contribution in addressing these shortcomings by designing a model-driving solution, emphasizing an integrated system conceptualized as a system of systems. This paper proposes a new methodology for designing an integrated and sustainable human settlement model, based on Model-Based Systems Engineering and a Systems Modeling Language to provide valuable insights toward sustainable solutions for displaced populations aligning with the United Nations 2030 agenda for sustainable development.
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.
文摘Due to the dynamic stiffness characteristics of human joints, it is easy to cause impact and disturbance on normal movements during exoskeleton assistance. This not only brings strict requirements for exoskeleton control design, but also makes it difficult to improve assistive level. The Variable Stiffness Actuator (VSA), as a physical variable stiffness mechanism, has the characteristics of dynamic stiffness adjustment and high stiffness control bandwidth, which is in line with the stiffness matching experiment. However, there are still few works exploring the assistive human stiffness matching experiment based on VSA. Therefore, this paper designs a hip exoskeleton based on VSA actuator and studies CPG human motion phase recognition algorithm. Firstly, this paper puts forward the requirements of variable stiffness experimental design and the output torque and variable stiffness dynamic response standards based on human lower limb motion parameters. Plate springs are used as elastic elements to establish the mechanical principle of variable stiffness, and a small variable stiffness actuator is designed based on the plate spring. Then the corresponding theoretical dynamic model is established and analyzed. Starting from the CPG phase recognition algorithm, this paper uses perturbation theory to expand the first-order CPG unit, obtains the phase convergence equation and verifies the phase convergence when using hip joint angle as the input signal with the same frequency, and then expands the second-order CPG unit under the premise of circular limit cycle and analyzes the frequency convergence criterion. Afterwards, this paper extracts the plate spring modal from Abaqus and generates the neutral file of the flexible body model to import into Adams, and conducts torque-stiffness one-way loading and reciprocating loading experiments on the variable stiffness mechanism. After that, Simulink is used to verify the validity of the criterion. Finally, based on the above criterions, the signal mean value is removed using feedback structure to complete the phase recognition algorithm for the human hip joint angle signal, and the convergence is verified using actual human walking data on flat ground.
基金a phased achievement of the MOE’s key philosophy and social science research project“Research on General Secretary Xi Jinping’s Discourses on Respecting and Protecting Human Rights”(Project Approval Number 22JZD002)MOE Humanities and Social Sciences Key Research Base’s major project“Research on the Theoretical Structure and Legal Guarantee of Digital Human Rights Governance”(Project Approval Number 21JJD8200014)。
文摘Xi Jinping’s discourses on respecting and protect-ing human rights stand as a shining example of the sinicization and modernization of Marxist human rights theory,embodying profound theoretical,political,practical,and cultural logic.Existing research has conducted comprehensive and systematic theoretical analysis and academic extractions on the following contents:the core essence in-herent in these important discourses,including the“theory of human rights concepts,”the“theory of human rights paths,”the“theory of human rights practices,”the“theory of human rights protection,”and the“theory of human rights governance,”along with their profound theoretical significance,practical significance,and global signifi-cance.In the future,researchers should emphasize efforts on studying the original texts and understanding the original principles.While focusing on the precision of concepts,the scientific nature of the prop-ositions,the maturity of theoretical systems,and the rigor of internal logic related to Xi Jinping’s discourses on respecting and protecting human rights,researchers should also pay attention to constructing a discourse system on human rights from the dimensions of discourse power,discourse cluster,and discourse field.Researchers should be adept at drawing innovative insights into human rights theory from China’s vibrant human rights practices and the vast masses of people.This approach will facilitate the systematic unfolding,academic trans-formation,and innovative development of Xi Jinping’s discourses on respecting and protecting human rights.
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.
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.
文摘In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
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.
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 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.
文摘Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.