The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and n...Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and neural tissues,thereby signifi-cantly impacting the health of both humans and animals.Animal models are crucial for studying virus pathogenesis,vaccine development,and drug testing.Despite several vaccine candidates being in preclinical and clinical stages,no vaccines are current available to prevent lifelong infections caused by these human herpesviruses,except for varicella-zoster virus(VZV)vaccine.However,the strict host tropism of herpes-viruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases.This makes it challeng-ing to evaluate vaccines and antivirals against human herpesvirus comprehensively.Herein,we summarize the current animal models used to study the human herpesvi-ruses includingα-herpesviruses(herpes simplex virus type 1(HSV-1),HSV-2,VZV),β-herpesviruses(human cytomegalovirus(HCMV),γ-herpesviruses(Epstein-Barr virus(EBV))and Kaposi's sarcoma herpesvirus(KSHV)).By providing concise information and detailed analysis of the potential,limitations and applications of various models,such as non-human primates,mice,rabbits,guinea pigs,and tree shrews,this sum-mary aims to help researchers efficiently select the most appropriate animal model,offering practical guidance for studying human herpesvirus.展开更多
Typically,seat or floor acceleration is used to evaluate the ride comfort of a high-speed train.However,the dynamic performance of the human body significantly differs from that of the floor.Therefore,using the car bo...Typically,seat or floor acceleration is used to evaluate the ride comfort of a high-speed train.However,the dynamic performance of the human body significantly differs from that of the floor.Therefore,using the car body floor and seat accelerations to calculate the ride comfort index of a high-speed train may not reflect the true feelings of passengers.In this study,a 3D human-seat-vehicle-track coupling model was established to investigate the ride comfort of highspeed train passengers.The seated human model,which considers the longitudinal,lateral,vertical,pitching,yawing,and rolling motions,comprises the head,upper torso,lower torso,pelvis,thighs,and shanks.The model parameters were determined using multi-axis excitation measurement data based on a genetic algorithm.Subsequently,the applicability of the small-angle assumption and natural modes of the human model is analyzed.Using the coupling system model,the vibration characteristics of the human-seat interaction surface were analyzed.The ride comfort of the high-speed train and human body dynamic performance were analyzed under normal conditions,track geometric irregularities and train meeting conditions.The results showed that the passenger seats in the front and rear rows adjacent to the window had a higher acceleration value than the others.The human backrest and seat pad connection points have higher vibration amplitudes than the car body floor in the human-sensitive frequency range,indicating that using the acceleration values on the floor may underestimate the discomfort of passengers.The ride comfort of high-speed trains diminishes in the presence of track geometric irregularities and when trains pass each other.When the excitation frequency of track geometry irregularities approached the natural frequency of the human-seat-vehicle system,ride comfort in high-speed trains decreased significantly.Moreover,using seat acceleration to evaluate passenger ride comfort overlooks the vibration characteristics of the human body.The transient aerodynamic force generated when the train meets can cause a larger car body roll and lateral motion at 2 Hz,which,in turn,decreases the passenger ride comfort.This study presents a detailed human-seat-vehicle-track coupling system that can reflect a passenger’s dynamic performance under complex operating conditions.展开更多
With the continuous development of artificial intelligence technology,large-scale language models have demonstrated significant potential across various fields.In education,an increasing number of methods leverage lar...With the continuous development of artificial intelligence technology,large-scale language models have demonstrated significant potential across various fields.In education,an increasing number of methods leverage large-scale language models to enhance educational quality,introducing new ideas and opportunities for reform.However,training a large language model with substantial professional knowledge to meet teaching needs incurs high labor costs.The fine-tuning approach based on human feedback alignment can significantly lower these model labor costs.Consequently,this article thoroughly investigates the application of this large prediction model method,which is rooted in human feed-back alignment,within the educational reform of algorithm analysis and design courses and examines its impact on teaching effectiveness and students’learning experiences.展开更多
Spillover of trypanosomiasis parasites from wildlife to domestic livestock and humans remains a major challenge world over.With the disease targeted for elimination by 2030,assessing the impact of control strategies i...Spillover of trypanosomiasis parasites from wildlife to domestic livestock and humans remains a major challenge world over.With the disease targeted for elimination by 2030,assessing the impact of control strategies in communities where there are human-cattle-wildlife interactions is therefore essential.A compartmental framework incorporating tsetse flies,humans,cattle,wildlife and various disease control strategies is developed and analyzed.The reproduction is derived and its sensitivity to different model parameters is investigated.Meanwhile,the optimal control theory is used to identify a combination of control strategies capable of minimizing the infected human and cattle population over time at minimal costs of implementation.The results indicates that tsetse fly mortality rate is strongly and negatively correlated to the reproduction number.It is also established that tsetse fly feeding rate in strongly and positively correlated to the reproduction number.Simulation results indicates that time dependent control strategies can significantly reduce the infections.Overall,the study shows that screening and treatment of humans may not lead to disease elimination.Combining this strategy with other strategies such as screening and treatment of cattle and vector control strategies will result in maximum reduction of tsetse fly population and disease elimination.展开更多
Enterprises are facing problems such as the dynamic matching of talents and strategies,and the construction of organizational resilience.Based on this,this paper deeply explores the significance of the research on the...Enterprises are facing problems such as the dynamic matching of talents and strategies,and the construction of organizational resilience.Based on this,this paper deeply explores the significance of the research on the“Double Helix”model of strategic human resource management in the VUCA era and the practical construction of the“Double Helix”model:the implementation path of key dimensions,aiming to achieve the coordinated progress of the two through strategies such as improving talent density,forging organizational resilience,and promoting the coordinated integration mechanism of the Double Helix,so as to provide scientific human resource management strategies for enterprises,help enterprises enhance their competitiveness in a complex and changeable environment,and achieve sustainable development.展开更多
Video action recognition(VAR)aims to analyze dynamic behaviors in videos and achieve semantic understanding.VAR faces challenges such as temporal dynamics,action-scene coupling,and the complexity of human interactions...Video action recognition(VAR)aims to analyze dynamic behaviors in videos and achieve semantic understanding.VAR faces challenges such as temporal dynamics,action-scene coupling,and the complexity of human interactions.Existing methods can be categorized into motion-level,event-level,and story-level ones based on spatiotemporal granularity.However,single-modal approaches struggle to capture complex behavioral semantics and human factors.Therefore,in recent years,vision-language models(VLMs)have been introduced into this field,providing new research perspectives for VAR.In this paper,we systematically review spatiotemporal hierarchical methods in VAR and explore how the introduction of large models has advanced the field.Additionally,we propose the concept of“Factor”to identify and integrate key information from both visual and textual modalities,enhancing multimodal alignment.We also summarize various multimodal alignment methods and provide in-depth analysis and insights into future research directions.展开更多
Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly ...Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).展开更多
Human motion modeling is a core technology in computer animation,game development,and humancomputer interaction.In particular,generating natural and coherent in-between motion using only the initial and terminal frame...Human motion modeling is a core technology in computer animation,game development,and humancomputer interaction.In particular,generating natural and coherent in-between motion using only the initial and terminal frames remains a fundamental yet unresolved challenge.Existing methods typically rely on dense keyframe inputs or complex prior structures,making it difficult to balance motion quality and plausibility under conditions such as sparse constraints,long-term dependencies,and diverse motion styles.To address this,we propose a motion generation framework based on a frequency-domain diffusion model,which aims to better model complex motion distributions and enhance generation stability under sparse conditions.Our method maps motion sequences to the frequency domain via the Discrete Cosine Transform(DCT),enabling more effective modeling of low-frequency motion structures while suppressing high-frequency noise.A denoising network based on self-attention is introduced to capture long-range temporal dependencies and improve global structural awareness.Additionally,a multi-objective loss function is employed to jointly optimize motion smoothness,pose diversity,and anatomical consistency,enhancing the realism and physical plausibility of the generated sequences.Comparative experiments on the Human3.6M and LaFAN1 datasets demonstrate that our method outperforms state-of-the-art approaches across multiple performance metrics,showing stronger capabilities in generating intermediate motion frames.This research offers a new perspective and methodology for human motion generation and holds promise for applications in character animation,game development,and virtual interaction.展开更多
The integration of the Lab model with the extended histogram of oriented gradients （EHOG） is proposed to improve the accuracy of human appearance matching across disjoint camera views under perturbations such as ill...The integration of the Lab model with the extended histogram of oriented gradients （EHOG） is proposed to improve the accuracy of human appearance matching across disjoint camera views under perturbations such as illumination changes and different viewing angles. For the Lab model that describes the global information of observations, a sorted nearest neighbor clustering method is proposed for color clustering and then a partitioned color matching method is used to calculate the color similarity between observations. The Bhattacharya distance is employed for the textural similarity calculation of the EHOG which describes the local information. The global information, which is robust to different viewing angles and scale changes, describes the observations well. Meanwhile, the use of local information, which is robust to illumination changes, can strengthen the discriminative ability of the method. The integration of global and local information improves the accuracy and robustness of the proposed matching approach. Experiments are carried out indoors, and the results show a high matching accuracy of the proposed method.展开更多
This paper discusses some issues on human reliability model of time dependent human behavior. Some results of the crew reliability experiment on Tsinghua training simulator in China are given, Meanwhile, a case of ca...This paper discusses some issues on human reliability model of time dependent human behavior. Some results of the crew reliability experiment on Tsinghua training simulator in China are given, Meanwhile, a case of calculation for human error probability during anticipated transient without scram (ATWS) based on the data drew from the recent experiment is offered.展开更多
Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate ear...Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate early cardiac fate determination are conserved between Drosophila and vertebrates,flies can be used as a model test system to explore the genetic basis of cardiogenesis in human.In this project,about 3000 reccieve lethal gene lines were produced by P or EMS mutagenesis.With staining of antibodies against heart precussor cells of Drosophila ,about 200 lines were observed to show heart phenotype.In pilot studies of their function with RNAi technique,the RNAi phenotypes of several genes tested were observed,which were very similar to that of their mutants,showing heart tube defects or no heart precursors formation.Taking advantage of the advanced genetic information available in the Drosophila and human systems,we have identified about 50 human transcripts homologous to the Drosophila heart related gene candidates.Northern blot analysis for some of the human candidates showed that several genes were expressed in both adult and early embryonic tissues,which may help in the evaluation of candidate genes for human cardiogenesis.Our further experiments with transgenic flies generated with wild type and mutant forms of these candidate genes to examine for defects in cardiogenesis or cardiac function are under way.The candidate genes producing cardiac specific defects suggestive of similarities to the heart disease syndromes can then be pursued further as likely disease gene candidates.Such an approach is likely to provide a dramatic reduction of possible candidate genes,or to screen and identify mutations that may generate the disease in human.展开更多
Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human disea...Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,展开更多
In this study, a risk-based management model is developed and applied to an industrial zone. The models proposed by the United States Environmental Protection Agency and Han Bing have been improved by adding a residua...In this study, a risk-based management model is developed and applied to an industrial zone. The models proposed by the United States Environmental Protection Agency and Han Bing have been improved by adding a residual ratio of volatile organic compounds （VOC） after boiling and deleting the related parameters in half-life. Using this improved model, an integrated process was used to assess human health risk level in the study area. Compared with water quality analysis, the results highlight the importance of applying an integrated approach for decision making on risk levels and water protection. The results of this study demonstrated that： （1） Compared with these permissible level standards in China （GB 3838-2002） and National Primary Drinking Water Regulations of the United States, the residents＇ daily life had not been affected by the groundwater in this area （except for relative bad water quality of HB3-4 and HB3-6）; （2） The typical detected organic contaminants of all groundwater samples were chloroform, carbon tetrachloride, trichloroethylene and tetrachloroethene, and the pollution sources were mainly industrial sources by preliminary investigations; （3） As for groundwater, the non-carcinogenic risk values of all samples do not exceed the permissible level of 1.0 and the carcinogenic risk values are relatively lower than the permissible level of 1.00E-06 to 1.00E-04; （4） Drinking water pathway of trichloroethylene and tetrachloroethylene mainly contribute to increasing the health risk of residents＇ in study areas; （5） In terms of non-carcinogenic risk and carcinogenic risk, the health risk order for drinking water pathway and dermal contact pathway was： drinking water pathway 〉 dermal contact pathway.展开更多
Why humans have large brains with higher cognitive abilities is a question long asked by scientjsts.However,much remains unknown,especially the underlying genetic mechanisms.With the use of a transgenic mon key model,...Why humans have large brains with higher cognitive abilities is a question long asked by scientjsts.However,much remains unknown,especially the underlying genetic mechanisms.With the use of a transgenic mon key model,we showed that human-specific sequenee changes of a key brain development gene(Primary microcephaly 1,MCPH7)could result in detectable molecularand cognitive changes resembling human neoteny,a no table characteristic developed during human evolution.This study was published in National Science Review(Shi et al.,2019).展开更多
This paper proposes a method to predict nonlinear Pilot-Induced Oscillation(PIO)using an intelligent human pilot model.This method is based on a scalogram-based PIO metric,which uses wavelet transforms to analyze the ...This paper proposes a method to predict nonlinear Pilot-Induced Oscillation(PIO)using an intelligent human pilot model.This method is based on a scalogram-based PIO metric,which uses wavelet transforms to analyze the nonlinear characteristics of a time-varying system.The intelligent human pilot model includes three modules:perception module,decision and adaptive module,and execution module.Intelligent and adaptive features,including a neural network receptor,fuzzy decision and adaptation,are also introduced into the human pilot model to describe the behavior of the human pilot accommodating the nonlinear events.Furthermore,an algorithm is proposed to describe the procedure of the PIO prediction method with nonlinear evaluation cases.The prediction results obtained by numerical simulation are compared with the assessments of flight test data to validate the utility of the method.The flight test data were generated in the evaluation of the Smart-Cue/Smart-Gain,which is capable of reducing the PIO tendencies considerably.The results show that the method can be applied to predict the nonlinear PIO events by human pilot model simulation.展开更多
AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou an...AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PbS(control), respectively, and fecal samples of pigs from 0 to 7 d post infection(DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. the HRV was tested by real-time PCR(Rt-PCR). the sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography.RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an agedependent manner and shed HRV antigen of the sameinoculum, as demonstrated by Rt- PCR.Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal minipigs. Guizhou mini-pigs were more sensitive to HRV than bamma with respect to RV antigen shedding and clinical diarrhea.CONCLUSION: these results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.展开更多
The Qinghai-Tibet Plateau is the word＇s highest and largest plateau. Due to increasing demands for environment exploration and tourism, a large transitional area is required for altitude adaptation. Hehuang valley, w...The Qinghai-Tibet Plateau is the word＇s highest and largest plateau. Due to increasing demands for environment exploration and tourism, a large transitional area is required for altitude adaptation. Hehuang valley, which locates in the transition zone between the Loess Plateau and the Qinghai-Tibet Plateau, has convenient transportation and relatively low elevation. Our question is whether the geographic conditions here are appropriate for adapted stay before going into the Qinghai-Tibet Plateau. Therefore, in this study, we examined the potential use of ecological niche modeling （ENM） for mapping current and potential distribution patterns of human settlements. We chose the Maximum Entropy Method （Maxent）, an ENM which integrates climate, remote sensing and geographical data, to model distributions and assess land suitability for transition areas. After preprocessing and selection, the correlation between variables and spatial auto- correlation input data were removed and 106 occurrence points and 9 environmental layers were determined as the model inputs. The threshold- independent model performance was reasonable according to lO times model running, with the area under the curve （AUC） values being 0.917± 0.01, and 0.923±0.002 for test data. Cohen＇s kappa coefficient of model performance was 0.848. Results showed that 82.22% of the study extent was not suitable for human settlement. Of the remaining areas, highly suitable areas aceounted for 1.19%, moderately for 5.3% and marginally for 11.28%. These suitable areas totaled 418.79 km2, and 86.25% of the sample data was identified in the different gradient of suitable area.The decisive environmental factors were slope and two climate variables： mean diurnal temperature range and temperature seasonality. Our model showed a good performance in mapping and assessing human settlements. This study provides the first predicted potential habitat distribution map for human settlement in Ledu County, which could also help in land use management.展开更多
The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent...The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.展开更多
The human digital twin(HDT)emerges as a promising human-centric technology in Industry 5.0,but challenges remain in human modeling and simulation.Digital human modeling(DHM)provides solutions for modeling and simulati...The human digital twin(HDT)emerges as a promising human-centric technology in Industry 5.0,but challenges remain in human modeling and simulation.Digital human modeling(DHM)provides solutions for modeling and simulating human physical and cognitive aspects to support ergonomic analysis.However,it has limitations in real-time data usage,personalized services,and timely interaction.The emerging HDT concept offers new possibilities by integrating multi-source data and artificial intelligence for continuous monitoring and assessment.Hence,this paper reviews the evolution from DHM to HDT and proposes a unified HDT framework from a human factors perspective.The framework comprises the physical twin,the virtual twin,and the linkage between these two.The virtual twin integrates human modeling and AI engines to enable model-data-hybrid-enabled simulation.HDT can potentially upgrade traditional ergonomic methods to intelligent services through real-time analysis,timely feedback,and bidirectional interactions.Finally,the future perspectives of HDT for industrial applications as well as technical and social challenges are discussed.In general,this study outlines a human factors perspective on HDT for the first time,which is useful for cross-disciplinary research and human factors innovation to enhance the development of HDT in industry.展开更多
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金National Natural Science Foundation of China,Grant/Award Number:82222041 and 82241068CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-037 and 2023-I2M-2-001+1 种基金National Key Research and Development Project of China,Grant/Award Number:2023YFC2309000Beijing Natural Science Foundation,Grant/Award Number:Z220018。
文摘Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and neural tissues,thereby signifi-cantly impacting the health of both humans and animals.Animal models are crucial for studying virus pathogenesis,vaccine development,and drug testing.Despite several vaccine candidates being in preclinical and clinical stages,no vaccines are current available to prevent lifelong infections caused by these human herpesviruses,except for varicella-zoster virus(VZV)vaccine.However,the strict host tropism of herpes-viruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases.This makes it challeng-ing to evaluate vaccines and antivirals against human herpesvirus comprehensively.Herein,we summarize the current animal models used to study the human herpesvi-ruses includingα-herpesviruses(herpes simplex virus type 1(HSV-1),HSV-2,VZV),β-herpesviruses(human cytomegalovirus(HCMV),γ-herpesviruses(Epstein-Barr virus(EBV))and Kaposi's sarcoma herpesvirus(KSHV)).By providing concise information and detailed analysis of the potential,limitations and applications of various models,such as non-human primates,mice,rabbits,guinea pigs,and tree shrews,this sum-mary aims to help researchers efficiently select the most appropriate animal model,offering practical guidance for studying human herpesvirus.
基金Supported by National Natural Science Foundation of China(Grant No.U1934203)Research and Development Project of Science and Technology of China Railway Corporation(Grant No.P2023T002)。
文摘Typically,seat or floor acceleration is used to evaluate the ride comfort of a high-speed train.However,the dynamic performance of the human body significantly differs from that of the floor.Therefore,using the car body floor and seat accelerations to calculate the ride comfort index of a high-speed train may not reflect the true feelings of passengers.In this study,a 3D human-seat-vehicle-track coupling model was established to investigate the ride comfort of highspeed train passengers.The seated human model,which considers the longitudinal,lateral,vertical,pitching,yawing,and rolling motions,comprises the head,upper torso,lower torso,pelvis,thighs,and shanks.The model parameters were determined using multi-axis excitation measurement data based on a genetic algorithm.Subsequently,the applicability of the small-angle assumption and natural modes of the human model is analyzed.Using the coupling system model,the vibration characteristics of the human-seat interaction surface were analyzed.The ride comfort of the high-speed train and human body dynamic performance were analyzed under normal conditions,track geometric irregularities and train meeting conditions.The results showed that the passenger seats in the front and rear rows adjacent to the window had a higher acceleration value than the others.The human backrest and seat pad connection points have higher vibration amplitudes than the car body floor in the human-sensitive frequency range,indicating that using the acceleration values on the floor may underestimate the discomfort of passengers.The ride comfort of high-speed trains diminishes in the presence of track geometric irregularities and when trains pass each other.When the excitation frequency of track geometry irregularities approached the natural frequency of the human-seat-vehicle system,ride comfort in high-speed trains decreased significantly.Moreover,using seat acceleration to evaluate passenger ride comfort overlooks the vibration characteristics of the human body.The transient aerodynamic force generated when the train meets can cause a larger car body roll and lateral motion at 2 Hz,which,in turn,decreases the passenger ride comfort.This study presents a detailed human-seat-vehicle-track coupling system that can reflect a passenger’s dynamic performance under complex operating conditions.
文摘With the continuous development of artificial intelligence technology,large-scale language models have demonstrated significant potential across various fields.In education,an increasing number of methods leverage large-scale language models to enhance educational quality,introducing new ideas and opportunities for reform.However,training a large language model with substantial professional knowledge to meet teaching needs incurs high labor costs.The fine-tuning approach based on human feedback alignment can significantly lower these model labor costs.Consequently,this article thoroughly investigates the application of this large prediction model method,which is rooted in human feed-back alignment,within the educational reform of algorithm analysis and design courses and examines its impact on teaching effectiveness and students’learning experiences.
文摘Spillover of trypanosomiasis parasites from wildlife to domestic livestock and humans remains a major challenge world over.With the disease targeted for elimination by 2030,assessing the impact of control strategies in communities where there are human-cattle-wildlife interactions is therefore essential.A compartmental framework incorporating tsetse flies,humans,cattle,wildlife and various disease control strategies is developed and analyzed.The reproduction is derived and its sensitivity to different model parameters is investigated.Meanwhile,the optimal control theory is used to identify a combination of control strategies capable of minimizing the infected human and cattle population over time at minimal costs of implementation.The results indicates that tsetse fly mortality rate is strongly and negatively correlated to the reproduction number.It is also established that tsetse fly feeding rate in strongly and positively correlated to the reproduction number.Simulation results indicates that time dependent control strategies can significantly reduce the infections.Overall,the study shows that screening and treatment of humans may not lead to disease elimination.Combining this strategy with other strategies such as screening and treatment of cattle and vector control strategies will result in maximum reduction of tsetse fly population and disease elimination.
基金Horizontal Topic of Suzhou Institute of Industrial Technology:Design and Optimization of Digital Salary System for Intelligent Technology Enterprises(Project No.:SIITHT2024006078)。
文摘Enterprises are facing problems such as the dynamic matching of talents and strategies,and the construction of organizational resilience.Based on this,this paper deeply explores the significance of the research on the“Double Helix”model of strategic human resource management in the VUCA era and the practical construction of the“Double Helix”model:the implementation path of key dimensions,aiming to achieve the coordinated progress of the two through strategies such as improving talent density,forging organizational resilience,and promoting the coordinated integration mechanism of the Double Helix,so as to provide scientific human resource management strategies for enterprises,help enterprises enhance their competitiveness in a complex and changeable environment,and achieve sustainable development.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(No.LQ23F030001)the National Natural Science Foundation of China(No.62406280)+5 种基金the Autism Research Special Fund of Zhejiang Foundation for Disabled Persons(No.2023008)the Liaoning Province Higher Education Innovative Talents Program Support Project(No.LR2019058)the Liaoning Province Joint Open Fund for Key Scientific and Technological Innovation Bases(No.2021-KF-12-05)the Central Guidance on Local Science and Technology Development Fund of Liaoning Province(No.2023JH6/100100066)the Key Laboratory for Biomedical Engineering of Ministry of Education,Zhejiang University,Chinain part by the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning.
文摘Video action recognition(VAR)aims to analyze dynamic behaviors in videos and achieve semantic understanding.VAR faces challenges such as temporal dynamics,action-scene coupling,and the complexity of human interactions.Existing methods can be categorized into motion-level,event-level,and story-level ones based on spatiotemporal granularity.However,single-modal approaches struggle to capture complex behavioral semantics and human factors.Therefore,in recent years,vision-language models(VLMs)have been introduced into this field,providing new research perspectives for VAR.In this paper,we systematically review spatiotemporal hierarchical methods in VAR and explore how the introduction of large models has advanced the field.Additionally,we propose the concept of“Factor”to identify and integrate key information from both visual and textual modalities,enhancing multimodal alignment.We also summarize various multimodal alignment methods and provide in-depth analysis and insights into future research directions.
基金National Key R&D Program of China,Grant/Award Number:2023YFC3402000National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science,Grant/Award Number:2023SKLDRS0124。
文摘Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
基金supported by the National Natural Science Foundation of China(Grant No.72161034).
文摘Human motion modeling is a core technology in computer animation,game development,and humancomputer interaction.In particular,generating natural and coherent in-between motion using only the initial and terminal frames remains a fundamental yet unresolved challenge.Existing methods typically rely on dense keyframe inputs or complex prior structures,making it difficult to balance motion quality and plausibility under conditions such as sparse constraints,long-term dependencies,and diverse motion styles.To address this,we propose a motion generation framework based on a frequency-domain diffusion model,which aims to better model complex motion distributions and enhance generation stability under sparse conditions.Our method maps motion sequences to the frequency domain via the Discrete Cosine Transform(DCT),enabling more effective modeling of low-frequency motion structures while suppressing high-frequency noise.A denoising network based on self-attention is introduced to capture long-range temporal dependencies and improve global structural awareness.Additionally,a multi-objective loss function is employed to jointly optimize motion smoothness,pose diversity,and anatomical consistency,enhancing the realism and physical plausibility of the generated sequences.Comparative experiments on the Human3.6M and LaFAN1 datasets demonstrate that our method outperforms state-of-the-art approaches across multiple performance metrics,showing stronger capabilities in generating intermediate motion frames.This research offers a new perspective and methodology for human motion generation and holds promise for applications in character animation,game development,and virtual interaction.
基金The National Natural Science Foundation of China(No.60972001)the Science and Technology Plan of Suzhou City(No.SG201076)
文摘The integration of the Lab model with the extended histogram of oriented gradients （EHOG） is proposed to improve the accuracy of human appearance matching across disjoint camera views under perturbations such as illumination changes and different viewing angles. For the Lab model that describes the global information of observations, a sorted nearest neighbor clustering method is proposed for color clustering and then a partitioned color matching method is used to calculate the color similarity between observations. The Bhattacharya distance is employed for the textural similarity calculation of the EHOG which describes the local information. The global information, which is robust to different viewing angles and scale changes, describes the observations well. Meanwhile, the use of local information, which is robust to illumination changes, can strengthen the discriminative ability of the method. The integration of global and local information improves the accuracy and robustness of the proposed matching approach. Experiments are carried out indoors, and the results show a high matching accuracy of the proposed method.
文摘This paper discusses some issues on human reliability model of time dependent human behavior. Some results of the crew reliability experiment on Tsinghua training simulator in China are given, Meanwhile, a case of calculation for human error probability during anticipated transient without scram (ATWS) based on the data drew from the recent experiment is offered.
文摘Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate early cardiac fate determination are conserved between Drosophila and vertebrates,flies can be used as a model test system to explore the genetic basis of cardiogenesis in human.In this project,about 3000 reccieve lethal gene lines were produced by P or EMS mutagenesis.With staining of antibodies against heart precussor cells of Drosophila ,about 200 lines were observed to show heart phenotype.In pilot studies of their function with RNAi technique,the RNAi phenotypes of several genes tested were observed,which were very similar to that of their mutants,showing heart tube defects or no heart precursors formation.Taking advantage of the advanced genetic information available in the Drosophila and human systems,we have identified about 50 human transcripts homologous to the Drosophila heart related gene candidates.Northern blot analysis for some of the human candidates showed that several genes were expressed in both adult and early embryonic tissues,which may help in the evaluation of candidate genes for human cardiogenesis.Our further experiments with transgenic flies generated with wild type and mutant forms of these candidate genes to examine for defects in cardiogenesis or cardiac function are under way.The candidate genes producing cardiac specific defects suggestive of similarities to the heart disease syndromes can then be pursued further as likely disease gene candidates.Such an approach is likely to provide a dramatic reduction of possible candidate genes,or to screen and identify mutations that may generate the disease in human.
基金supported by the grants from the National Basic Research Program of China(973 Program) awarded to N.L.(No.2011CBA01000) and L.L.(No. 2011CB944203)
文摘Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,
基金supported by National Science and Technology Major Project(No2009 ZX 05039-003,2009 ZX 05039-004,2011ZX05060-005)the National Natural Science Foundation of China(No 2010CB428801-1)state-owned land resources investigation(1212010430351)
文摘In this study, a risk-based management model is developed and applied to an industrial zone. The models proposed by the United States Environmental Protection Agency and Han Bing have been improved by adding a residual ratio of volatile organic compounds （VOC） after boiling and deleting the related parameters in half-life. Using this improved model, an integrated process was used to assess human health risk level in the study area. Compared with water quality analysis, the results highlight the importance of applying an integrated approach for decision making on risk levels and water protection. The results of this study demonstrated that： （1） Compared with these permissible level standards in China （GB 3838-2002） and National Primary Drinking Water Regulations of the United States, the residents＇ daily life had not been affected by the groundwater in this area （except for relative bad water quality of HB3-4 and HB3-6）; （2） The typical detected organic contaminants of all groundwater samples were chloroform, carbon tetrachloride, trichloroethylene and tetrachloroethene, and the pollution sources were mainly industrial sources by preliminary investigations; （3） As for groundwater, the non-carcinogenic risk values of all samples do not exceed the permissible level of 1.0 and the carcinogenic risk values are relatively lower than the permissible level of 1.00E-06 to 1.00E-04; （4） Drinking water pathway of trichloroethylene and tetrachloroethylene mainly contribute to increasing the health risk of residents＇ in study areas; （5） In terms of non-carcinogenic risk and carcinogenic risk, the health risk order for drinking water pathway and dermal contact pathway was： drinking water pathway 〉 dermal contact pathway.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)the National Natural Science Foundation of China(31730088)the Youth Innovation Promotion Association of CAS
文摘Why humans have large brains with higher cognitive abilities is a question long asked by scientjsts.However,much remains unknown,especially the underlying genetic mechanisms.With the use of a transgenic mon key model,we showed that human-specific sequenee changes of a key brain development gene(Primary microcephaly 1,MCPH7)could result in detectable molecularand cognitive changes resembling human neoteny,a no table characteristic developed during human evolution.This study was published in National Science Review(Shi et al.,2019).
基金co-supported by the National Natural Science Foundation of China (No. 11502008)the Aeronautical Science Foundation of China (No. 2017ZA51002)
文摘This paper proposes a method to predict nonlinear Pilot-Induced Oscillation(PIO)using an intelligent human pilot model.This method is based on a scalogram-based PIO metric,which uses wavelet transforms to analyze the nonlinear characteristics of a time-varying system.The intelligent human pilot model includes three modules:perception module,decision and adaptive module,and execution module.Intelligent and adaptive features,including a neural network receptor,fuzzy decision and adaptation,are also introduced into the human pilot model to describe the behavior of the human pilot accommodating the nonlinear events.Furthermore,an algorithm is proposed to describe the procedure of the PIO prediction method with nonlinear evaluation cases.The prediction results obtained by numerical simulation are compared with the assessments of flight test data to validate the utility of the method.The flight test data were generated in the evaluation of the Smart-Cue/Smart-Gain,which is capable of reducing the PIO tendencies considerably.The results show that the method can be applied to predict the nonlinear PIO events by human pilot model simulation.
基金Supported by National Natural Science Foundation of China,No.30400402 and No.30571708
文摘AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PbS(control), respectively, and fecal samples of pigs from 0 to 7 d post infection(DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. the HRV was tested by real-time PCR(Rt-PCR). the sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography.RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an agedependent manner and shed HRV antigen of the sameinoculum, as demonstrated by Rt- PCR.Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal minipigs. Guizhou mini-pigs were more sensitive to HRV than bamma with respect to RV antigen shedding and clinical diarrhea.CONCLUSION: these results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.
基金supported by the Natural Science Foundation of China (Grant No. 41171330)National High Technology Research and Development Program of China (863 Program)(Grant No. 2013AA12A302)the Special Foundation for Free Exploration of State Laboratory of Remote Sensing Science (Grant No.Y1Y00245KZ)
文摘The Qinghai-Tibet Plateau is the word＇s highest and largest plateau. Due to increasing demands for environment exploration and tourism, a large transitional area is required for altitude adaptation. Hehuang valley, which locates in the transition zone between the Loess Plateau and the Qinghai-Tibet Plateau, has convenient transportation and relatively low elevation. Our question is whether the geographic conditions here are appropriate for adapted stay before going into the Qinghai-Tibet Plateau. Therefore, in this study, we examined the potential use of ecological niche modeling （ENM） for mapping current and potential distribution patterns of human settlements. We chose the Maximum Entropy Method （Maxent）, an ENM which integrates climate, remote sensing and geographical data, to model distributions and assess land suitability for transition areas. After preprocessing and selection, the correlation between variables and spatial auto- correlation input data were removed and 106 occurrence points and 9 environmental layers were determined as the model inputs. The threshold- independent model performance was reasonable according to lO times model running, with the area under the curve （AUC） values being 0.917± 0.01, and 0.923±0.002 for test data. Cohen＇s kappa coefficient of model performance was 0.848. Results showed that 82.22% of the study extent was not suitable for human settlement. Of the remaining areas, highly suitable areas aceounted for 1.19%, moderately for 5.3% and marginally for 11.28%. These suitable areas totaled 418.79 km2, and 86.25% of the sample data was identified in the different gradient of suitable area.The decisive environmental factors were slope and two climate variables： mean diurnal temperature range and temperature seasonality. Our model showed a good performance in mapping and assessing human settlements. This study provides the first predicted potential habitat distribution map for human settlement in Ledu County, which could also help in land use management.
基金supported by grants from the Cancer Institutes of the National Institute of HealthCurrent funding comes from CA 83679the Anderson Family Endowed Chair in Medical Education,Research and Patient Care
文摘The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.
基金Supported by National Natural Science Foundation of China(Grant No.72071179)ZJU-Sunon Joint Research Center of Smart Furniture,Zhejiang University,China.
文摘The human digital twin(HDT)emerges as a promising human-centric technology in Industry 5.0,but challenges remain in human modeling and simulation.Digital human modeling(DHM)provides solutions for modeling and simulating human physical and cognitive aspects to support ergonomic analysis.However,it has limitations in real-time data usage,personalized services,and timely interaction.The emerging HDT concept offers new possibilities by integrating multi-source data and artificial intelligence for continuous monitoring and assessment.Hence,this paper reviews the evolution from DHM to HDT and proposes a unified HDT framework from a human factors perspective.The framework comprises the physical twin,the virtual twin,and the linkage between these two.The virtual twin integrates human modeling and AI engines to enable model-data-hybrid-enabled simulation.HDT can potentially upgrade traditional ergonomic methods to intelligent services through real-time analysis,timely feedback,and bidirectional interactions.Finally,the future perspectives of HDT for industrial applications as well as technical and social challenges are discussed.In general,this study outlines a human factors perspective on HDT for the first time,which is useful for cross-disciplinary research and human factors innovation to enhance the development of HDT in industry.
