In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabdi...In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues： （1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.展开更多
Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxicological and neurological studies.Generating genet...Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxicological and neurological studies.Generating genetic tools to manipulate neurons in rats could benefit neurological research.Methods:Using the CRISPR/Cas9 system,we inserted a Cre cassette into endogenous Thy1 and NeuN loci.Thy1-Cre rats featured a downstream P2A-linked insertion,while NeuN-Cre was inserted at the transcriptional start site.The Cre activity was assessed by crossing with a Cre reporter(Rosa26 imCherry)rat and through analyzing mCherry expression patterns.The specificity of cell type was further confirmed by immunofluorescence with NeuN antibody.Phenotypic consequences were assessed by crossing with ND1^(LSL) rats to deplete ND1,followed by monitoring weight/survival and conducting motor function tests.Results:We generated two neuron-specific rats(Thy1-Cre and NeuN-Cre),which exhibited high neuron-specific Cre expression in brain and spinal cord with minor leakage in other tissues.Thy1-Cre showed minor leakage in spleen,lung and kidney while NeuN-Cre showed minor leakage in spleen and kidney.ND1^(Thy1-Cre) and ND1^(NeuN-Cre) rats both showed decreased body weights and survival times.The ND1^(NeuN-Cre) rats died within two weeks,while ND1^(Thy1-Cre) rats lived longer with impaired motor function.Conclusions:We successfully generated two neuron-specific NeuN-Cre and Thy1-Cre rats,and systemically analyzed their expression pattern.展开更多
Non-human primates （NHPs） are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biom...Non-human primates （NHPs） are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China＇s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China＇s life sciences and pharmaceutical industry, and enhance China＇s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective to better utilize NHP resources and further foster NHP research in China.展开更多
Aim： To show whether molecular motor dynein on a microtubule track, molecular motor myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein （MyRIP）, and vesicle receptor Rab27b on an F-actin track w...Aim： To show whether molecular motor dynein on a microtubule track, molecular motor myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein （MyRIP）, and vesicle receptor Rab27b on an F-actin track were present during human and monkey spermiogenesis involving intramanchette transport （IMT）. Methods： Spermiogenic cells were obtained from three men with obstructive azoospermia and normal adult cynomolgus monkey （Macacafascieularis）. Immunocytochemical detection and reverse transcription-polymerase chain reaction （RT-PCR） analysis of the proteins were carried out. Samples were analyzed by light microscope. Results： Using RT-PCR, we found that dynein, myosin Va, MyRIP and Rab27b were expressed in monkey testis. These proteins were localized to the manchette, as shown by immunofluorescence, particularly during human and monkey spermiogenesis. Conclusion： We speculate that during primate spermiogenesis, those proteins that compose microtubule-based and actin-based vesicle transport systems are actually present in the manchette and might possibly be involved in intramanchette transport.展开更多
Recent studies have shown that fibroblast transplantation can modify the activity of basal ganglia networks in models of Parkinson＇s disease. To determine its effects on parkinsonian motor symptoms, we performed auto...Recent studies have shown that fibroblast transplantation can modify the activity of basal ganglia networks in models of Parkinson＇s disease. To determine its effects on parkinsonian motor symptoms, we performed autologous dermal fibroblast transplantation into the internal pallidum （GPi） in two parkinsonian rhesus monkeys with stable levodopa- induced dyskinesias （LIDs）. Levodopa responses were assessed every week after transplantation for three months. A reduction of between 58% and 64% in total LIDs on the contralateral side was observed in both animals. No clear LID changes were observed on the ipsilateral side. These effects lasted the entire 3-month period in one monkey, but declined after 6-8 weeks in the other. The antiparkinsonian effects of levodopa did not diminish, The results of this pilot study indicate that fibroblast transplantation into the GPi may have beneficial effects on LIDs and warrant further investigation for potential therapeutic use.展开更多
Human noroviruses(No V) are associated with large proportion of non-bacterial diarrhea outbreaks together with > 50% of food-associated diarrheas. The function of histo-blood group antigens(HBGAs) in pathogenesis o...Human noroviruses(No V) are associated with large proportion of non-bacterial diarrhea outbreaks together with > 50% of food-associated diarrheas. The function of histo-blood group antigens(HBGAs) in pathogenesis of virus infection was implicated. Until recently however, due to lack of a robust animal and in vitro models of human NoV infection, only the partial knowledge concerning the virus pathogenesis(receptor, coreceptor and target cell) and absence of viable vaccine candidates were the frequently referenced attributes of this acute diarrheal illness. Recently, a novel group of enteric caliciviruses(CV) of rhesus macaque host origin was discovered and described. The new genus within the family Caliciviridae was identified: Rhesus Enteric CV, i.e., "Recovirus"(Re CV). Re CVs are genetically and biologically close relatives of human NoV s, exhibit similar genetic and biological features and are capable of being propagated in cell culture. ReC Vs cause symptomatic disease(diarrhea and fever) in experimentally inoculated macaques. Formulation and evaluation of efficient NoV vaccine might take several years. As suggested by recent studies, inhibition of HBGAs or HBGAbased antivirals could meanwhile be exploited as vaccine alternatives. The purpose of this minireview is to provide the guidance in respect to newly available primate model of enteric CV infection and its similarities with human NoV in utilizing the HBGAs as potential virus co-receptors to indirectly address the unresolved questions of NoV pathogenesis and immunity.展开更多
Primates are highly successful mammals with significant morphological,behavioral,and physiological diversity.Studying the genomes of non-human primates,as the closest relative of humans,can provide insights into human...Primates are highly successful mammals with significant morphological,behavioral,and physiological diversity.Studying the genomes of non-human primates,as the closest relative of humans,can provide insights into human evolution,genetic structure,and potential drug targets relevant to human health,thus making important contributions to medical research.Additionally,primate genome research can support ecological balance and resource conservation and promote sustainable development and human well-being.Despite the existence of more than 500 primate species belonging to 80 genera and 16 families worldwide,with new species still being discovered in recent years(Fan et al.,2017;Khanal et al.,2021;Roos et al.,2020),genome sequencing efforts have been limited to a relatively small number of species from only 22 genera(Ensembl v103).Notably,approximately 72%of primate genera remain unsequenced,leading to significant knowledge gaps in our understanding of their evolutionary history.This situation presents considerable challenges for the development,utilization,and protection of primate genetic resources.It is for these compelling reasons that we initiated the Primate Genome Project(PGP)(Wu et al.,2022).展开更多
A crucial step for understanding human evolution is to identify the genomic changes that occurred during primate evolution,thus allowing investigators to reconstruct the ancestral states preceding the human condition....A crucial step for understanding human evolution is to identify the genomic changes that occurred during primate evolution,thus allowing investigators to reconstruct the ancestral states preceding the human condition.In the past several decades,the primate clade has been a research focus in genome sequencing due to its unique phylogenetic position and key importance.展开更多
From 2 to 4 November, 2016, the 4th Symposium on Animal Models of Non-Human Primates （NHP） was held in Kunming, Yunnan, China. This meeting was organized by the Key Laboratory of Animal Models and Human Disease Mech...From 2 to 4 November, 2016, the 4th Symposium on Animal Models of Non-Human Primates （NHP） was held in Kunming, Yunnan, China. This meeting was organized by the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences （CAS） ＆ Yunnan Province Kunming Primate Research Center （KPRC）, Zoological Research, and Kunming Institute of Zoology （KIZ）, CAS.展开更多
The culture of mammalian cells is closely related to the development of biotechnology, which has been used extensively in the research and application fields of biology and medical science. In this article, various fa...The culture of mammalian cells is closely related to the development of biotechnology, which has been used extensively in the research and application fields of biology and medical science. In this article, various factors affecting cell cultivation and the application of microcarrier and bioreactor on large-scale culture of mammalian ceils were reviewed.展开更多
A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the ...A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the macaque fasicularis monkey that measures electromyographic data from the musculature of the tail. As well, previous experiments have demonstrated that selective lesions can be created in the lower thoracic spinal cord that does not cause limb weakness and/or bowel dysfunction. The histopathological features of these lesions appear similar to human TSCI. This paper describes a method by which the EMG data can be transformed into a quantitative metric of volitional limb movement (“Q”). This metric permits an objective assessment of injury, natural recovery as well as potential efficacy of candidate treatments.展开更多
Background and objective: Generating and characterizing primate models of epileptic seizures are important for understanding pathophysiology of diseases and establishing preclinical efficacy of novel therapies like De...Background and objective: Generating and characterizing primate models of epileptic seizures are important for understanding pathophysiology of diseases and establishing preclinical efficacy of novel therapies like Deep Brain Stimulation. A focal motor epilepsy model is described here. Method: Seizures were obtained after intracortical penicillin injection into the motor strip through a cannula in two awake monkeys and electrocorticograms were recorded by epidural screws. Seizures were analyzed and compared for number, average duration of each seizure and total duration of ictal activity. Pharmaco-resistance for antiepileptic drug was tested by administration of Diazepam during seizures. Results: A motor status with seizures mimicking those seen in Kojevnikov’s syndrome was easily generated several minutes after penicillin injection and lasted 24 h on an average. The model thus characterized appears stable and consistent. There is no significant variation between experiments in individual primate as well as between two specimens. Diazepam though reduced the total duration of seizures, failed to abolish behavioural seizures. Conclusion: This model represents a good alternative model for preclinical research aiming at testing novel therapies because seizures are obtained on demand, last up to 24 h after a single penicillin injection, are stable and resistant to Diazepam.展开更多
This study investigates the relationships between exposures to ambient air pollution—specifically particulate matter 2.5 (PM_(2.5)) and its metabolites—and the risk of depression.Nonlinear and linear regression,Baye...This study investigates the relationships between exposures to ambient air pollution—specifically particulate matter 2.5 (PM_(2.5)) and its metabolites—and the risk of depression.Nonlinear and linear regression,Bayesian kernel machine regression,and toxicogenomic analysis were key approaches.PM_(2.5)exposure was positively associated with the risk of developing depression,whereas phenylglyoxylic acid exposure was negatively associated with depression risk.We found a significant overall relationship between ambient air pollution and depression,particularly at the 55th and 60th percentiles.Although statistical significance was not reached at the 65th percentile,there was a noticeable upward trend,indicating a potential association.Interestingly,no significant connection was found between a combination of metabolites from ambient air pollution and depression.PM_(2.5)and phenylglyoxylic acid emerged as the most influential compounds in the models,respectively.PM_(2.5)exposure altered the expression of 42 specific targets associated with depression,especially POMC,SCL6A4,IL6,and SOD2.The study identified specific pathways related to insulin secretion,energy metabolism,blood circulation,tube diameter,and maintenance of blood vessel diameter,as well as key molecular mechanisms involving hsa-miR-124-3p,hsa-miR-155-5p,hsa-miR-16-5p,and SP1.These mechanisms were found to underlie the etiology of depression associated with PM_(2.5)exposure.In conclusions,PM_(2.5)and phenylglyoxylic acid were found to be associated with depression.Further work is needed to gain insight into the molecular mechanisms by which these chemicals affect depression,especially pathways related to insulin secretion and blood circulation.展开更多
The Himalayan monal(Lophophorus impejanus),Nepal’s national bird,is a protected species facing significant conservation challenges.Understanding the distribution and habitat preferences of the Himalayan monal(HM)is c...The Himalayan monal(Lophophorus impejanus),Nepal’s national bird,is a protected species facing significant conservation challenges.Understanding the distribution and habitat preferences of the Himalayan monal(HM)is crucial for its conservation.This study was conducted in the Langtang National Park(LNP),Nepal using the route census method during both winter(November/December 2022)and summer(June 2023)seasons to examine the seasonal variation in HM’s elevational distribution and habitat preference.Further,we assessed their conservation threats by conducting a semi-structured questionnaire survey with the local residents.During the winter period,the HMs preferred grassland habitats,while in the summer,their preference shifted to shrubland and barren area.HM abundance was negatively associated with the Normalized Differential Vegetation Index(NDVI)and the shortest distance from the survey trails in the winter.The HMs actively avoided areas with high anthropogenic pressure.In the summer,they showed a wider elevational range up to 4400 m above sea level(a.s.l.),with a higher sighting frequency between 3600 and 3900 m a.s.l.The questionnaire survey of the local residents revealed that anthropogenic pressure such as poaching and free-ranging livestock grazing are the major threats to the species in the study area.This study provides valuable insight into the complex habitat preferences and critical threats faced by the HMs in LNP and underscores the urgent need for targeted conservation action.展开更多
Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,p...Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.展开更多
The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatom...The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatomy of this species remains insufficiently defined,limiting its utility in neurophysiological and neuropathological studies.In this study,immunofluorescence microscopy was employed to comprehensively map the distribution of three calciumbinding proteins,parvalbumin,calbindin D-28k,and calretinin,across the tree shrew cerebrum.Serial brain sections in sagittal,coronal,and horizontal planes from 12 individuals generated a dataset of 3638 cellular-resolution images.This dataset,accessible via Science Data Bank(https://doi.org/10.57760/sciencedb.23471),provides detailed region-and laminar-selective distributions of calcium-binding proteins valuable for the cyto-and chemoarchitectural characterization of the tree shrew cerebrum.This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.展开更多
Automated behavior monitoring of macaques offers transformative potential for advancing biomedical research and animal welfare.However,reliably identifying individual macaques in group environments remains a significa...Automated behavior monitoring of macaques offers transformative potential for advancing biomedical research and animal welfare.However,reliably identifying individual macaques in group environments remains a significant challenge.This study introduces ACE-YOLOX,a lightweight facial recognition model tailored for captive macaques.ACE-YOLOX incorporates Efficient Channel Attention(ECA),Complete Intersection over Union loss(CIoU),and Adaptive Spatial Feature Fusion(ASFF)into the YOLOX framework,enhancing prediction accuracy while reducing computational complexity.These integrated approaches enable effective multiscale feature extraction.Using a dataset comprising 179400 labeled facial images from 1196 macaques,ACE-YOLOX surpassed the performance of classical object detection models,demonstrating superior accuracy and real-time processing capabilities.An Android application was also developed to deploy ACE-YOLOX on smartphones,enabling on-device,real-time macaque recognition.Our experimental results highlight the potential of ACE-YOLOX as a non-invasive identification tool,offering an important foundation for future studies in macaque facial expression recognition,cognitive psychology,and social behavior.展开更多
BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammatio...BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammation.It affects patients’survival,functional status,and quality of life profoundly.Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia.The gut microbiota,through its intricate interplay with iron metabolism,inflammatory pathways,and immune modulation,may either exacerbate or ameliorate anemia depending on its composition,and functional integrity.Dysbiosis,characterized by disruption in the gut microbial ecosystem,is very common in cancer patients.This microbial imbalance is implicated in anemia causation through diminished iron absorption,persistent low-grade inflammation,and suppression of erythropoiesis.AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies.It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia,identifies unique challenges associated with various cancer types,and evaluates the efficacy of microbiome-focused therapies.Through this integrative approach,the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.METHODS A literature search was performed using multiple databases,including Google Scholar,PubMed,Scopus,and Web of Science,using a combination of keywords and Boolean operators to refine results.Keywords included“cancerassociated anemia”,“gut microbiome”,“intestinal microbiota”,“iron metabolism”,“gut dysbiosis”,“short-chain fatty acids”,“hematopoiesis”,“probiotics”,“prebiotics”,and“fecal microbiota transplantation”.Articles published in English between 2000 and December 2024 were included,with a focus on contemporary and relevant findings.RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis,such as probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation(FMT),can inhibit anemia-causing pathways by enhancing microbial diversity,suppressing detrimental flora,reducing systemic inflammation and optimizing nutrient absorption.CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients.Microbiome-centered interventions,such as probiotics,prebiotics,dietary modifications,and FMT,have shown efficacy in restoring microbial balance,reducing inflammation,and enhancing nutrient bioavailability.Emerging approaches,including engineered probiotics and bacteriophage therapies,are promising precision-based,customizable solutions for various microbiome compositions and imbalances.Future research should focus on integrating microbiometargeted strategies with established anemia therapies.展开更多
文摘In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues： （1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.
基金Research Project of China Baoyuan Investment Co.,Ltd,Grant/Award Number:Program CBYI202102Haihe Laboratory of Cell Ecosystem Innovation Fund,Grant/Award Number:HH24KYZX0007+4 种基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-024,2021-I2M-1-034 and 2023-I2M-2-001Fundamental Research Funds for the Central Universities,Grant/Award Number:3332022040 and 3332023164Open Research Project in State Key Laboratory of Vascular Homeostasis and Remodeling,Peking University,Grant/Award Number:202411State Key Laboratory Special Fund,Grant/Award Number:2060204the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01.
文摘Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxicological and neurological studies.Generating genetic tools to manipulate neurons in rats could benefit neurological research.Methods:Using the CRISPR/Cas9 system,we inserted a Cre cassette into endogenous Thy1 and NeuN loci.Thy1-Cre rats featured a downstream P2A-linked insertion,while NeuN-Cre was inserted at the transcriptional start site.The Cre activity was assessed by crossing with a Cre reporter(Rosa26 imCherry)rat and through analyzing mCherry expression patterns.The specificity of cell type was further confirmed by immunofluorescence with NeuN antibody.Phenotypic consequences were assessed by crossing with ND1^(LSL) rats to deplete ND1,followed by monitoring weight/survival and conducting motor function tests.Results:We generated two neuron-specific rats(Thy1-Cre and NeuN-Cre),which exhibited high neuron-specific Cre expression in brain and spinal cord with minor leakage in other tissues.Thy1-Cre showed minor leakage in spleen,lung and kidney while NeuN-Cre showed minor leakage in spleen and kidney.ND1^(Thy1-Cre) and ND1^(NeuN-Cre) rats both showed decreased body weights and survival times.The ND1^(NeuN-Cre) rats died within two weeks,while ND1^(Thy1-Cre) rats lived longer with impaired motor function.Conclusions:We successfully generated two neuron-specific NeuN-Cre and Thy1-Cre rats,and systemically analyzed their expression pattern.
基金supported by the National Natural Science Foundation of China(81172876,81273251,U1202228,81471620)the National Special Science Research Program of China(2012CBA01305)+1 种基金the National Science and Technology Major Project(2013ZX10001-002,2012ZX10001-007)the Knowledge Innovation Program of CAS(KSCX2-EW-R-13,KJZD-EW-L10-02)
文摘Non-human primates （NHPs） are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China＇s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China＇s life sciences and pharmaceutical industry, and enhance China＇s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective to better utilize NHP resources and further foster NHP research in China.
文摘Aim： To show whether molecular motor dynein on a microtubule track, molecular motor myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein （MyRIP）, and vesicle receptor Rab27b on an F-actin track were present during human and monkey spermiogenesis involving intramanchette transport （IMT）. Methods： Spermiogenic cells were obtained from three men with obstructive azoospermia and normal adult cynomolgus monkey （Macacafascieularis）. Immunocytochemical detection and reverse transcription-polymerase chain reaction （RT-PCR） analysis of the proteins were carried out. Samples were analyzed by light microscope. Results： Using RT-PCR, we found that dynein, myosin Va, MyRIP and Rab27b were expressed in monkey testis. These proteins were localized to the manchette, as shown by immunofluorescence, particularly during human and monkey spermiogenesis. Conclusion： We speculate that during primate spermiogenesis, those proteins that compose microtubule-based and actin-based vesicle transport systems are actually present in the manchette and might possibly be involved in intramanchette transport.
基金supported by grants from the National Institutes of Health (NS045962, NS073994, NCRR RR000165 and ORIP/OD OD011132)Forum Pharmaceuticals, Inc.Gene Graft, Ltd
文摘Recent studies have shown that fibroblast transplantation can modify the activity of basal ganglia networks in models of Parkinson＇s disease. To determine its effects on parkinsonian motor symptoms, we performed autologous dermal fibroblast transplantation into the internal pallidum （GPi） in two parkinsonian rhesus monkeys with stable levodopa- induced dyskinesias （LIDs）. Levodopa responses were assessed every week after transplantation for three months. A reduction of between 58% and 64% in total LIDs on the contralateral side was observed in both animals. No clear LID changes were observed on the ipsilateral side. These effects lasted the entire 3-month period in one monkey, but declined after 6-8 weeks in the other. The antiparkinsonian effects of levodopa did not diminish, The results of this pilot study indicate that fibroblast transplantation into the GPi may have beneficial effects on LIDs and warrant further investigation for potential therapeutic use.
文摘Human noroviruses(No V) are associated with large proportion of non-bacterial diarrhea outbreaks together with > 50% of food-associated diarrheas. The function of histo-blood group antigens(HBGAs) in pathogenesis of virus infection was implicated. Until recently however, due to lack of a robust animal and in vitro models of human NoV infection, only the partial knowledge concerning the virus pathogenesis(receptor, coreceptor and target cell) and absence of viable vaccine candidates were the frequently referenced attributes of this acute diarrheal illness. Recently, a novel group of enteric caliciviruses(CV) of rhesus macaque host origin was discovered and described. The new genus within the family Caliciviridae was identified: Rhesus Enteric CV, i.e., "Recovirus"(Re CV). Re CVs are genetically and biologically close relatives of human NoV s, exhibit similar genetic and biological features and are capable of being propagated in cell culture. ReC Vs cause symptomatic disease(diarrhea and fever) in experimentally inoculated macaques. Formulation and evaluation of efficient NoV vaccine might take several years. As suggested by recent studies, inhibition of HBGAs or HBGAbased antivirals could meanwhile be exploited as vaccine alternatives. The purpose of this minireview is to provide the guidance in respect to newly available primate model of enteric CV infection and its similarities with human NoV in utilizing the HBGAs as potential virus co-receptors to indirectly address the unresolved questions of NoV pathogenesis and immunity.
文摘Primates are highly successful mammals with significant morphological,behavioral,and physiological diversity.Studying the genomes of non-human primates,as the closest relative of humans,can provide insights into human evolution,genetic structure,and potential drug targets relevant to human health,thus making important contributions to medical research.Additionally,primate genome research can support ecological balance and resource conservation and promote sustainable development and human well-being.Despite the existence of more than 500 primate species belonging to 80 genera and 16 families worldwide,with new species still being discovered in recent years(Fan et al.,2017;Khanal et al.,2021;Roos et al.,2020),genome sequencing efforts have been limited to a relatively small number of species from only 22 genera(Ensembl v103).Notably,approximately 72%of primate genera remain unsequenced,leading to significant knowledge gaps in our understanding of their evolutionary history.This situation presents considerable challenges for the development,utilization,and protection of primate genetic resources.It is for these compelling reasons that we initiated the Primate Genome Project(PGP)(Wu et al.,2022).
基金supported by the National Natural Science Foundation of China(31822048)Strategic Priority Research Program of the Chinese Academy of Sciences(XDPB17)。
文摘A crucial step for understanding human evolution is to identify the genomic changes that occurred during primate evolution,thus allowing investigators to reconstruct the ancestral states preceding the human condition.In the past several decades,the primate clade has been a research focus in genome sequencing due to its unique phylogenetic position and key importance.
基金supported by the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province,KPRC,KIZ,CAS,and Zoology Research
文摘From 2 to 4 November, 2016, the 4th Symposium on Animal Models of Non-Human Primates （NHP） was held in Kunming, Yunnan, China. This meeting was organized by the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences （CAS） ＆ Yunnan Province Kunming Primate Research Center （KPRC）, Zoological Research, and Kunming Institute of Zoology （KIZ）, CAS.
基金Supported by Post-doctoral Fund of China(20070410923)Youth Science Fund of Heilongjiang(QC06C014)+1 种基金Post-doctoral Fund of HeilongjiangDoctoral Fund of Northeast Agricultural University
文摘The culture of mammalian cells is closely related to the development of biotechnology, which has been used extensively in the research and application fields of biology and medical science. In this article, various factors affecting cell cultivation and the application of microcarrier and bioreactor on large-scale culture of mammalian ceils were reviewed.
文摘A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the macaque fasicularis monkey that measures electromyographic data from the musculature of the tail. As well, previous experiments have demonstrated that selective lesions can be created in the lower thoracic spinal cord that does not cause limb weakness and/or bowel dysfunction. The histopathological features of these lesions appear similar to human TSCI. This paper describes a method by which the EMG data can be transformed into a quantitative metric of volitional limb movement (“Q”). This metric permits an objective assessment of injury, natural recovery as well as potential efficacy of candidate treatments.
基金supported by“Fondation de l’avenir”and Medtronic Europe.
文摘Background and objective: Generating and characterizing primate models of epileptic seizures are important for understanding pathophysiology of diseases and establishing preclinical efficacy of novel therapies like Deep Brain Stimulation. A focal motor epilepsy model is described here. Method: Seizures were obtained after intracortical penicillin injection into the motor strip through a cannula in two awake monkeys and electrocorticograms were recorded by epidural screws. Seizures were analyzed and compared for number, average duration of each seizure and total duration of ictal activity. Pharmaco-resistance for antiepileptic drug was tested by administration of Diazepam during seizures. Results: A motor status with seizures mimicking those seen in Kojevnikov’s syndrome was easily generated several minutes after penicillin injection and lasted 24 h on an average. The model thus characterized appears stable and consistent. There is no significant variation between experiments in individual primate as well as between two specimens. Diazepam though reduced the total duration of seizures, failed to abolish behavioural seizures. Conclusion: This model represents a good alternative model for preclinical research aiming at testing novel therapies because seizures are obtained on demand, last up to 24 h after a single penicillin injection, are stable and resistant to Diazepam.
文摘This study investigates the relationships between exposures to ambient air pollution—specifically particulate matter 2.5 (PM_(2.5)) and its metabolites—and the risk of depression.Nonlinear and linear regression,Bayesian kernel machine regression,and toxicogenomic analysis were key approaches.PM_(2.5)exposure was positively associated with the risk of developing depression,whereas phenylglyoxylic acid exposure was negatively associated with depression risk.We found a significant overall relationship between ambient air pollution and depression,particularly at the 55th and 60th percentiles.Although statistical significance was not reached at the 65th percentile,there was a noticeable upward trend,indicating a potential association.Interestingly,no significant connection was found between a combination of metabolites from ambient air pollution and depression.PM_(2.5)and phenylglyoxylic acid emerged as the most influential compounds in the models,respectively.PM_(2.5)exposure altered the expression of 42 specific targets associated with depression,especially POMC,SCL6A4,IL6,and SOD2.The study identified specific pathways related to insulin secretion,energy metabolism,blood circulation,tube diameter,and maintenance of blood vessel diameter,as well as key molecular mechanisms involving hsa-miR-124-3p,hsa-miR-155-5p,hsa-miR-16-5p,and SP1.These mechanisms were found to underlie the etiology of depression associated with PM_(2.5)exposure.In conclusions,PM_(2.5)and phenylglyoxylic acid were found to be associated with depression.Further work is needed to gain insight into the molecular mechanisms by which these chemicals affect depression,especially pathways related to insulin secretion and blood circulation.
基金an MSc thesis research grant from the Zoological Society of London(ZSL)Nepal.RCK’s effort was supported in part by the Office of Research Infrastructure Programs(ORIP)of the National Institutes of Health through grant number P51OD010425 to the Washington National Primate Research Center,USA。
文摘The Himalayan monal(Lophophorus impejanus),Nepal’s national bird,is a protected species facing significant conservation challenges.Understanding the distribution and habitat preferences of the Himalayan monal(HM)is crucial for its conservation.This study was conducted in the Langtang National Park(LNP),Nepal using the route census method during both winter(November/December 2022)and summer(June 2023)seasons to examine the seasonal variation in HM’s elevational distribution and habitat preference.Further,we assessed their conservation threats by conducting a semi-structured questionnaire survey with the local residents.During the winter period,the HMs preferred grassland habitats,while in the summer,their preference shifted to shrubland and barren area.HM abundance was negatively associated with the Normalized Differential Vegetation Index(NDVI)and the shortest distance from the survey trails in the winter.The HMs actively avoided areas with high anthropogenic pressure.In the summer,they showed a wider elevational range up to 4400 m above sea level(a.s.l.),with a higher sighting frequency between 3600 and 3900 m a.s.l.The questionnaire survey of the local residents revealed that anthropogenic pressure such as poaching and free-ranging livestock grazing are the major threats to the species in the study area.This study provides valuable insight into the complex habitat preferences and critical threats faced by the HMs in LNP and underscores the urgent need for targeted conservation action.
基金National Resources Center for Non Human PrimatesNational Key R&D Project of China,Grant/Award Number:2021YFF0702804。
文摘Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.
基金supported by the Science and Technology Innovation(STI)2030-Major Projects(2022ZD0205000 to L.L.)CAS“Light of West China”Program(xbzg-zdsys-202404 to L.L.)+1 种基金Yunnan Revitalization Talent Support Program Yunling Scholar Project(to L.L.)Yunnan Fundamental Research Projects(202305AH340006,202301AS070060 to L.L.,202401AT070206 to X.C.)。
文摘The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatomy of this species remains insufficiently defined,limiting its utility in neurophysiological and neuropathological studies.In this study,immunofluorescence microscopy was employed to comprehensively map the distribution of three calciumbinding proteins,parvalbumin,calbindin D-28k,and calretinin,across the tree shrew cerebrum.Serial brain sections in sagittal,coronal,and horizontal planes from 12 individuals generated a dataset of 3638 cellular-resolution images.This dataset,accessible via Science Data Bank(https://doi.org/10.57760/sciencedb.23471),provides detailed region-and laminar-selective distributions of calcium-binding proteins valuable for the cyto-and chemoarchitectural characterization of the tree shrew cerebrum.This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.
基金supported by the grants from Yunnan Province(202305AH340006,202305AH340007)CAS Light of West China Program(xbzg-zdsys-202213)。
文摘Automated behavior monitoring of macaques offers transformative potential for advancing biomedical research and animal welfare.However,reliably identifying individual macaques in group environments remains a significant challenge.This study introduces ACE-YOLOX,a lightweight facial recognition model tailored for captive macaques.ACE-YOLOX incorporates Efficient Channel Attention(ECA),Complete Intersection over Union loss(CIoU),and Adaptive Spatial Feature Fusion(ASFF)into the YOLOX framework,enhancing prediction accuracy while reducing computational complexity.These integrated approaches enable effective multiscale feature extraction.Using a dataset comprising 179400 labeled facial images from 1196 macaques,ACE-YOLOX surpassed the performance of classical object detection models,demonstrating superior accuracy and real-time processing capabilities.An Android application was also developed to deploy ACE-YOLOX on smartphones,enabling on-device,real-time macaque recognition.Our experimental results highlight the potential of ACE-YOLOX as a non-invasive identification tool,offering an important foundation for future studies in macaque facial expression recognition,cognitive psychology,and social behavior.
文摘BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammation.It affects patients’survival,functional status,and quality of life profoundly.Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia.The gut microbiota,through its intricate interplay with iron metabolism,inflammatory pathways,and immune modulation,may either exacerbate or ameliorate anemia depending on its composition,and functional integrity.Dysbiosis,characterized by disruption in the gut microbial ecosystem,is very common in cancer patients.This microbial imbalance is implicated in anemia causation through diminished iron absorption,persistent low-grade inflammation,and suppression of erythropoiesis.AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies.It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia,identifies unique challenges associated with various cancer types,and evaluates the efficacy of microbiome-focused therapies.Through this integrative approach,the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.METHODS A literature search was performed using multiple databases,including Google Scholar,PubMed,Scopus,and Web of Science,using a combination of keywords and Boolean operators to refine results.Keywords included“cancerassociated anemia”,“gut microbiome”,“intestinal microbiota”,“iron metabolism”,“gut dysbiosis”,“short-chain fatty acids”,“hematopoiesis”,“probiotics”,“prebiotics”,and“fecal microbiota transplantation”.Articles published in English between 2000 and December 2024 were included,with a focus on contemporary and relevant findings.RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis,such as probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation(FMT),can inhibit anemia-causing pathways by enhancing microbial diversity,suppressing detrimental flora,reducing systemic inflammation and optimizing nutrient absorption.CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients.Microbiome-centered interventions,such as probiotics,prebiotics,dietary modifications,and FMT,have shown efficacy in restoring microbial balance,reducing inflammation,and enhancing nutrient bioavailability.Emerging approaches,including engineered probiotics and bacteriophage therapies,are promising precision-based,customizable solutions for various microbiome compositions and imbalances.Future research should focus on integrating microbiometargeted strategies with established anemia therapies.
