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
Viruses circulating in small mammals possess the potential to infect humans.Tree shrews are a group of small mammals inhabiting widely in forests and plantations,but studies on viruses in tree shrews are quite limited...Viruses circulating in small mammals possess the potential to infect humans.Tree shrews are a group of small mammals inhabiting widely in forests and plantations,but studies on viruses in tree shrews are quite limited.Herein,viral metagenomic sequencing was employed to detect the virome in the tissue and swab samples from seventy-six tree shrews that we collected in Yunnan Province.As the results,genomic fragments belonging to eighteen viral families were identified,thirteen of which contain mammalian viruses.Through polymerase chain reaction(PCR)and Sanger sequencing,twelve complete genomes were determined,including five parvoviruses,three torque teno viruses(TTVs),two adenoviruses,one pneumovirus,and one hepacivirus,together with three partial genomes,including two hepatitis E viruses and one paramyxovirus.Notably,the three TTVs,named TSTTV-HNU1,TSTTV-HNU2,and TSTTV-HNU3,may compose a new genus within the family Anelloviridae.Notably,TSParvoV-HNU5,one of the tree shrew parvoviruses detected,was likely to be a recombination of two murine viruses.Divergence time estimation further revealed the potential cross-species-transmission history of the tree shrew pneumovirus TSPneV-HNU1.Our study provides a comprehensive exploration of viral diversity in wild tree shrews,significantly enhancing our understanding of their roles as natural virus reservoirs.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their produc...The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.Th...The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.展开更多
Due to their special phylogenetic position in the Euarchontoglires and close affinity to primates,tree shrews have been proposed as an alternative experimental animal to primates in biomedical research.However,the pop...Due to their special phylogenetic position in the Euarchontoglires and close affinity to primates,tree shrews have been proposed as an alternative experimental animal to primates in biomedical research.However,the population genetic structure of tree shrews has largely remained unknown and this has hindered the development of tree shrew breeding and selection.Here we sampled 80 Chinese tree shrews（Tupaia belangeri chinensis） in Kunming,China,and analyzed partial mtDNA control region sequence variation.Based on our samples and two published sequences from northern tree shrews（T.belangeri）,we identified 29 substitutions in the mtDNA control region fragment（～ 604 bp） across 82 individuals and defined 13 haplotypes.Seventeen samples were selected for sequencing of the cytochrome b（Cyt b;1134 bp） gene based on control region sequence variation and were analyzed in combination with 34 published sequences to solidify the phylogenetic pattern obtained from control region data.Overall,tree shrews from Kunming have high genetic diversity and present a remarkable long genetic distance to the two reported northern tree shrews outside China.Our results provide some caution when using tree shrews to establish animal models because of this apparent genetic difference.In addition,the high genetic diversity of Chinese tree shrews inhabiting Kunming suggests that systematic genetic investigations should be conducted before establishing an inbred strain for medical and biological research.展开更多
Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolution...Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolutionary relationship with humans than do rodents,which have been widely used in laboratory research.Spontaneous breast tumors were identified in tree shrews in 1960s;however,no detailed studies about tree shrew breast tumors have been conducted to date.Here,we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin（HE） staining.This tumor was identified as a papillary tumor.Immunohistochemical staining（IHC） for progesterone receptor（PR）,Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR,highly proliferative,and less apoptotic compared to normal breast epithelial cells.Thus,the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.展开更多
Neural stem cells promote neuronal regeneration and repair of brain tissue after injury,but have limited resources and proliferative ability in vivo.We hypothesized that nerve growth factor would promote in vitro prol...Neural stem cells promote neuronal regeneration and repair of brain tissue after injury,but have limited resources and proliferative ability in vivo.We hypothesized that nerve growth factor would promote in vitro proliferation of neural stem cells derived from the tree shrews,a primate-like mammal that has been proposed as an alternative to primates in biomedical translational research.We cultured neural stem cells from the hippocampus of tree shrews at embryonic day 38,and added nerve growth factor（100 μg/L） to the culture medium.Neural stem cells from the hippocampus of tree shrews cultured without nerve growth factor were used as controls.After 3 days,fluorescence microscopy after DAPI and nestin staining revealed that the number of neurospheres and DAPI/nestin-positive cells was markedly greater in the nerve growth factor-treated cells than in control cells.These findings demonstrate that nerve growth factor promotes the proliferation of neural stem cells derived from tree shrews.展开更多
On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by...On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.展开更多
Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and ...Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.展开更多
Endosymbionts influence many aspects of their hosts’ health conditions, including physiology, development, immunity, metabolism, etc. Tree shrews(Tupaia belangeri chinensis) have attracted increasing attention in mod...Endosymbionts influence many aspects of their hosts’ health conditions, including physiology, development, immunity, metabolism, etc. Tree shrews(Tupaia belangeri chinensis) have attracted increasing attention in modeling human diseases and therapeutic responses due to their close relationship with primates. To clarify the situation of symbiotic bacteria from their body surface, oral cavity, and anus, 12 wild and 12 the third generation of captive tree shrews were examined. Based on morphological and cultural characteristics, physiological and biochemical tests, as well as the 16 S rDNA full sequence analysis, 12 bacteria strains were isolated and identified from the wild tree shrews: body surface: Bacillus subtilis(detection rate 42%), Pseudomonas aeruginosa(25%), Staphlococcus aureus(33%), S. Epidermidis(75%), Micrococcus luteus(25%), Kurthia gibsonii(17%); oral cavity: Neisseria mucosa(58%), Streptococcus pneumonia(17%); anus: Enterococcus faecalis(17%), Lactococus lactis(33%), Escherichia coli(92%), Salmonella typhosa(17%); whereas, four were indentified from the third generation captive tree shrews: body surface: S. epidermidis(75%); oral cavity: N.mucosa(67%); anus: L. lactis(33%), E. coli(100%). These results indicate that S. epidermidis, N. mucosa, L. lactis and E. coli were major bacteria in tree shrews, whereas, S. aureus, M. luteus, K. gibsonii, E. faecalis and S. typhosa were species-specific flora. This study facilitates the future use of tree shrews as a standard experimental animal and improves our understanding of the relationship between endosymbionts and their hosts.展开更多
Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of fe...Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.展开更多
Liver transplantation (LT)is most effective and promising approach for end-stage liver disease.However,there remains room for further improvement and innovation,for example, to reduce ischemic reperfusion injury,trans...Liver transplantation (LT)is most effective and promising approach for end-stage liver disease.However,there remains room for further improvement and innovation,for example, to reduce ischemic reperfusion injury,transplant rejection and immune tolerance.A good animal model of LT is essential for such innovation in transplant research.Although rat LT model has been used since the last century,it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other.In this study,we for the first time performed LT using the tree shrew (Tupaia belangeri),a species in the Order Scandentia which is closely related with primates,and evaluated the possibility to adopt this species as a new model of LT.We performed LT on 30 animals using the two-cuff technique, examining the success rate,the survival rate and the immunological reaction.The recipient operation time was 60 min averagely,and we limited the time of the anhepatic phase within 20 min.Twenty-seven (90%)of the animals survived for at least 3 days after the transplantation. Thirteen animals that did not receive any immunosuppressive drug died in 8 days mostly because of acute rejection effect (n=9),similar to the reaction in human but not in experimental rat.The rest 14 animals that were given rapamycin survived significantly longer (38 days)and half of them survived for 60 days until the end of the study.Our results suggest that performing LT in tree shrews can yield high success rate and high survival rate.More importantly,the tree shrews share similar immunological reaction with human.In addition,previous genomics study found that the tree shrews share more proteins with human.In sum,the tree shrews may outperform the experimental rats and could be used as a better and cost-effective animal model for LT.展开更多
To characterize the patterns of ABR waves in tree shrews, we must understand the hearing sensitivity and auditory function of healthy adult tree shrews. Fifteen tree shrews(30 ears) were stimulated with clicks and ton...To characterize the patterns of ABR waves in tree shrews, we must understand the hearing sensitivity and auditory function of healthy adult tree shrews. Fifteen tree shrews(30 ears) were stimulated with clicks and tone-pips at 11 different frequencies from 1 to 60 kHz. The ABR waves were recorded and analyzed. The ABR consisted of five to seven positive waves in the first 10 ms after a click stimulus, and the average hearing threshold of component III was 27.86 ± 3.78 dB SPL. Wave III was the largest and most clear. The ABR threshold was related to the tone-pip sitmulus by a "U" shaped curve. The sensitive frequency was approximately 8 kHz in tree shrews. The latencies systematically decreased with increasing stimulus frequencies. The ABR amplitudes of wave III increased as the sound pressure level increased. All of these results provide an empirical basis for future studies of hearing diseases in tree shrews.展开更多
Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feed...Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1)body weight,(2)core body temperature and rhythm,(3)diet metabolism,(4)locomotor rhythm,(5)electroencephalogram,(6)glycometabolism and(7)serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that(a)the core body temperature of the tree shrew was 39.59±0.05°C,which was higher than that of rats and macaques;(b)Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30;(c)Compared with rats,tree shrews had poor carbohydrate metabolism ability;and(d)Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.展开更多
As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveill...As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained （conception rate=74%）. Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.展开更多
Backgroud: Current understanding of injury and regeneration of islet β-cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of prim...Backgroud: Current understanding of injury and regeneration of islet β-cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of primates, and has been widely used in animal experimentation. However, there are few reports on islet cell composition and regeneration of β-cells in tree shrews.Methods: In this study, we examined the changes in islet cell composition and regeneration of β-cells after streptozotocin(STZ) treatment in tree shrews compared with Sprague-Dawley rats. Injury and regeneration of islet β-cells were observed using hematoxylin and eosin(HE) staining and immunohistochemical staining for insulin, glucagon, somatostatin and PDX-1.Results: Our data showed that in rats islet injury was most obvious on day 3 after injection, and islet morphologies were significantly restored by day 21. Regeneration of islet β-cells was very pronounced in rats, and mainly involved regeneration of centro-acinar cells and transformation of extra-islet ductal cells. In tree shrews, the regeneration of islet β-cells was not as significant. On days 3 and 7, only scattered regenerated cells were observed in the remaining islets. Further, no regeneration of centro-acinar cells was observed.Conclusion: The results suggest that the repair mechanism of islet β-cells in tree shrews is similar to that of humans.展开更多
OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups:...OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.展开更多
Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial...Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial architecture.However,the anatomical distribution and morphological characteristics of astrocytes in the tree shrew brain remain poorly characterized.In this study,glial fibrillary acidic protein(GFAP)immunofluorescence was employed to systematically examine the spatial distribution and morphology of astrocytes in the whole brain of tree shrews.Notably,GFAP-immunoreactive(ir)astrocytes were detected throughout the telencephalon,diencephalon,mesencephalon,metencephalon,and myelencephalon.Distinct laminar distribution was evident in regions such as the main olfactory bulb and hippocampus.Semi-quantitative comparisons revealed significant regional differences in astrocyte density between tree shrews and mice,encompassing the main olfactory bulb,accessory olfactory bulb,olfactory tubercle,cortex,hippocampus,cortical amygdaloid nucleus,hypothalamus,thalamus,superior colliculus,interpeduncular nucleus,median raphe nucleus,and parabrachial nucleus.Compared to mice,tree shrews exhibited higher astrocyte density with increased morphological complexity in the posterior hypothalamic nucleus,dorsomedial hypothalamic nucleus,ventromedial hypothalamic nucleus,and periaqueductal gray,but lower density with greater morphological complexity in the hippocampus and substantia nigra.In the paraventricular hypothalamic nucleus and lateral hypothalamic area,GFAP-ir astrocytes displayed comparable densities between tree shrews and mice but exhibited region-specific differences in morphological complexity.This study provides the first brain-wide mapping of GFAP-ir astrocytes in tree shrews,revealing marked interspecies differences in their distribution and morphology,and establishing a neuroanatomical framework for understanding astrocyte involvement in diverse physiological and behavioral functions.展开更多
Background It has been known that platelet activating factor receptors （PAFR） may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B （GB） possesses multiple effects, but the actions of...Background It has been known that platelet activating factor receptors （PAFR） may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B （GB） possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment. Methods Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow （rCBF, using ^99rnTc tracer technique ）, the brain water content （specific gravimetric method）, PAFR （3H-labelled PAF assay）, the respiratory control rate （RCR）, the phosphorus-oxygen （P/O） ratio of mitochondrial respiration （Clark oxygen electrode）, mitochonddal permeability transition （MPT） pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups （the ischemia group vs the sham group, and the ischemia group vs the GB group）. Results There were high affinity and low affinity sites for PAFR on the tree threws＇ brain cell membranes. The varying-affinity PAFR binding sites, the respiration state Ⅲ, the state Ⅳ, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly （respectively, P〈0.01 and P〈0.05）, but the water content increased （P〈0.01） in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB （5 mg/kg i.v.） 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated （P〈0.01） at 24h after cerebral ischemia. There were significant differences between the ischemJa group and sham group （P〈0.01）. In GB treated isolated neurons＇ mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed. Conclusions The activation of the PAFR may play an important role in the inhibition of the mitochondrial respiration and the induction of neuronal damage after cerebral thrombosis; however, GB possesses neuroprotective effects by improving mitochondrial metabolism.展开更多
The well-accepted Euarchonta grandorder is a pruned version of Archonta nested within the Euarchontoglires(or Supraprimates)clade.At present,it includes tree shrews(Scandentia),flying lemurs(Dermoptera)and primates(Pr...The well-accepted Euarchonta grandorder is a pruned version of Archonta nested within the Euarchontoglires(or Supraprimates)clade.At present,it includes tree shrews(Scandentia),flying lemurs(Dermoptera)and primates(Primates).Here,a phylogenomic dataset containing 1912 exons from 22 representative mammals was compiled to investigate the phylogenetic relationships within this group.Phylogenetic analyses and hypothesis testing suggested that tree shrews can be classified as a sister group to Primates or to Glires or even as a basal clade within Euarchontoglires.Further analyses of both modified and original previously published datasets found that the phylogenetic position of tree shrews is unstable.We also found that two of three exonic indels reported as synapomorphies of Euarchonta in a previous study do not unambiguously support the monophyly of such a clade.Therefore,the monophyly of both Euarchonta and Sundatheria(Dermoptera+Scandentia)are suspect.Molecular dating and divergence rate analyses suggested that the ancestor of Euarchontoglires experienced a rapid divergence,which may cause the unresolved position of tree shrews even using the whole genomic data.展开更多
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funded by the National Natural Science Foundation of China(No.U2002218)the Science and Technology Innovation Program of Hunan Province(2024RC1028)Hunan University(No.521119400156).
文摘Viruses circulating in small mammals possess the potential to infect humans.Tree shrews are a group of small mammals inhabiting widely in forests and plantations,but studies on viruses in tree shrews are quite limited.Herein,viral metagenomic sequencing was employed to detect the virome in the tissue and swab samples from seventy-six tree shrews that we collected in Yunnan Province.As the results,genomic fragments belonging to eighteen viral families were identified,thirteen of which contain mammalian viruses.Through polymerase chain reaction(PCR)and Sanger sequencing,twelve complete genomes were determined,including five parvoviruses,three torque teno viruses(TTVs),two adenoviruses,one pneumovirus,and one hepacivirus,together with three partial genomes,including two hepatitis E viruses and one paramyxovirus.Notably,the three TTVs,named TSTTV-HNU1,TSTTV-HNU2,and TSTTV-HNU3,may compose a new genus within the family Anelloviridae.Notably,TSParvoV-HNU5,one of the tree shrew parvoviruses detected,was likely to be a recombination of two murine viruses.Divergence time estimation further revealed the potential cross-species-transmission history of the tree shrew pneumovirus TSPneV-HNU1.Our study provides a comprehensive exploration of viral diversity in wild tree shrews,significantly enhancing our understanding of their roles as natural virus reservoirs.
基金supported by the Key Research and Development Program of Guangxi(2021AB13014)Major Project of Guangxi Innovation Driven(AA18118016)+7 种基金National Key Research and Development Program of China(2017YFC0908000)Natural Key Research and Development Project(2020YFA0113200)National Natural Science Foundation of China(81770759,82060145,31970814)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2021JJA140912)Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University,Guangxi Key Laboratory for Genomic and Personalized Medicine(19-050-22,19-185-33,20-065-33,22-35-17)Major Project of Scientific Research and Technology Development Plan of Nanning(20221023)Guangxi Natural Science Foundation(2022GXNSFAA035641)Self-funded Project of Health Commission of Guangxi Zhuang Autonomous Region(Z-A20230620)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.
基金supported by the National Key R&D Program of China (2021YFC2300900,2021YFC2301300)Academic Promotion Programme of Shandong First Medical University (2019QL006)+2 种基金Natural Science Foundation of Shandong Province (ZR2020QH274)Yunnan Key Research and Development Program (202103AQ100001,202102AA310055)Key Program of Chinese Academy of Sciences (KJZD-SW-L11)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.
基金supported by grants from Yunnan Province (2009CI119)the Chinese Academy of Sciences (KSCX2-EW-R-11 and KSCX2-EW-J-23)the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province
文摘Due to their special phylogenetic position in the Euarchontoglires and close affinity to primates,tree shrews have been proposed as an alternative experimental animal to primates in biomedical research.However,the population genetic structure of tree shrews has largely remained unknown and this has hindered the development of tree shrew breeding and selection.Here we sampled 80 Chinese tree shrews（Tupaia belangeri chinensis） in Kunming,China,and analyzed partial mtDNA control region sequence variation.Based on our samples and two published sequences from northern tree shrews（T.belangeri）,we identified 29 substitutions in the mtDNA control region fragment（～ 604 bp） across 82 individuals and defined 13 haplotypes.Seventeen samples were selected for sequencing of the cytochrome b（Cyt b;1134 bp） gene based on control region sequence variation and were analyzed in combination with 34 published sequences to solidify the phylogenetic pattern obtained from control region data.Overall,tree shrews from Kunming have high genetic diversity and present a remarkable long genetic distance to the two reported northern tree shrews outside China.Our results provide some caution when using tree shrews to establish animal models because of this apparent genetic difference.In addition,the high genetic diversity of Chinese tree shrews inhabiting Kunming suggests that systematic genetic investigations should be conducted before establishing an inbred strain for medical and biological research.
基金Yunnan Province High-Profile Talent Project (2010CI114)the Chinese Academy of Sciences,Basic Frontier Project (KSCX2-EW-J-23)
文摘Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolutionary relationship with humans than do rodents,which have been widely used in laboratory research.Spontaneous breast tumors were identified in tree shrews in 1960s;however,no detailed studies about tree shrew breast tumors have been conducted to date.Here,we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin（HE） staining.This tumor was identified as a papillary tumor.Immunohistochemical staining（IHC） for progesterone receptor（PR）,Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR,highly proliferative,and less apoptotic compared to normal breast epithelial cells.Thus,the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.
基金supported by a grant from the National Key Technology Research and Development Program of the Ministry of Science and Technology of China,No.2014BAI01B00
文摘Neural stem cells promote neuronal regeneration and repair of brain tissue after injury,but have limited resources and proliferative ability in vivo.We hypothesized that nerve growth factor would promote in vitro proliferation of neural stem cells derived from the tree shrews,a primate-like mammal that has been proposed as an alternative to primates in biomedical translational research.We cultured neural stem cells from the hippocampus of tree shrews at embryonic day 38,and added nerve growth factor（100 μg/L） to the culture medium.Neural stem cells from the hippocampus of tree shrews cultured without nerve growth factor were used as controls.After 3 days,fluorescence microscopy after DAPI and nestin staining revealed that the number of neurospheres and DAPI/nestin-positive cells was markedly greater in the nerve growth factor-treated cells than in control cells.These findings demonstrate that nerve growth factor promotes the proliferation of neural stem cells derived from tree shrews.
文摘On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.
基金supported by the National High-Tech R&D Program(2014ZX09102042)the National Natural Science Foundation of China(81373142)the Natural Science Foundation of Yunnan Province(2012ZA009)
文摘Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.
基金This study was supported by the National 863 Project of China （2012AA021801） and the Project of Frontier Study of Foundation, CAS （KSCX2-EW-R-11, KSCX2-EW-J-23）
文摘Endosymbionts influence many aspects of their hosts’ health conditions, including physiology, development, immunity, metabolism, etc. Tree shrews(Tupaia belangeri chinensis) have attracted increasing attention in modeling human diseases and therapeutic responses due to their close relationship with primates. To clarify the situation of symbiotic bacteria from their body surface, oral cavity, and anus, 12 wild and 12 the third generation of captive tree shrews were examined. Based on morphological and cultural characteristics, physiological and biochemical tests, as well as the 16 S rDNA full sequence analysis, 12 bacteria strains were isolated and identified from the wild tree shrews: body surface: Bacillus subtilis(detection rate 42%), Pseudomonas aeruginosa(25%), Staphlococcus aureus(33%), S. Epidermidis(75%), Micrococcus luteus(25%), Kurthia gibsonii(17%); oral cavity: Neisseria mucosa(58%), Streptococcus pneumonia(17%); anus: Enterococcus faecalis(17%), Lactococus lactis(33%), Escherichia coli(92%), Salmonella typhosa(17%); whereas, four were indentified from the third generation captive tree shrews: body surface: S. epidermidis(75%); oral cavity: N.mucosa(67%); anus: L. lactis(33%), E. coli(100%). These results indicate that S. epidermidis, N. mucosa, L. lactis and E. coli were major bacteria in tree shrews, whereas, S. aureus, M. luteus, K. gibsonii, E. faecalis and S. typhosa were species-specific flora. This study facilitates the future use of tree shrews as a standard experimental animal and improves our understanding of the relationship between endosymbionts and their hosts.
基金supported by grants from the Chinese Academy of Sciences (KSCX2-EW-R-12, KSCX2-EW-J-23)the National Natural Science Foundation of China (81171294)Shanghai Science & Technology Development Foundation(12140904200)
文摘Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.
基金the grants from National Natural Science Foundation of China(No.81660407)Applied Basic Research Project of Yunnan Provincial Science and Technology Department(No.2014FB053)Health Department of Yunnan Province Agency Project(No.2014NS063).
文摘Liver transplantation (LT)is most effective and promising approach for end-stage liver disease.However,there remains room for further improvement and innovation,for example, to reduce ischemic reperfusion injury,transplant rejection and immune tolerance.A good animal model of LT is essential for such innovation in transplant research.Although rat LT model has been used since the last century,it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other.In this study,we for the first time performed LT using the tree shrew (Tupaia belangeri),a species in the Order Scandentia which is closely related with primates,and evaluated the possibility to adopt this species as a new model of LT.We performed LT on 30 animals using the two-cuff technique, examining the success rate,the survival rate and the immunological reaction.The recipient operation time was 60 min averagely,and we limited the time of the anhepatic phase within 20 min.Twenty-seven (90%)of the animals survived for at least 3 days after the transplantation. Thirteen animals that did not receive any immunosuppressive drug died in 8 days mostly because of acute rejection effect (n=9),similar to the reaction in human but not in experimental rat.The rest 14 animals that were given rapamycin survived significantly longer (38 days)and half of them survived for 60 days until the end of the study.Our results suggest that performing LT in tree shrews can yield high success rate and high survival rate.More importantly,the tree shrews share similar immunological reaction with human.In addition,previous genomics study found that the tree shrews share more proteins with human.In sum,the tree shrews may outperform the experimental rats and could be used as a better and cost-effective animal model for LT.
基金supported by Natural Science Foundation of China[grant numbers 81760188]Scientific Research Fund of Guangxi Provincial Education Department [grant numbers 2017KY0103 (02601217023C)]
文摘To characterize the patterns of ABR waves in tree shrews, we must understand the hearing sensitivity and auditory function of healthy adult tree shrews. Fifteen tree shrews(30 ears) were stimulated with clicks and tone-pips at 11 different frequencies from 1 to 60 kHz. The ABR waves were recorded and analyzed. The ABR consisted of five to seven positive waves in the first 10 ms after a click stimulus, and the average hearing threshold of component III was 27.86 ± 3.78 dB SPL. Wave III was the largest and most clear. The ABR threshold was related to the tone-pip sitmulus by a "U" shaped curve. The sensitive frequency was approximately 8 kHz in tree shrews. The latencies systematically decreased with increasing stimulus frequencies. The ABR amplitudes of wave III increased as the sound pressure level increased. All of these results provide an empirical basis for future studies of hearing diseases in tree shrews.
基金This work was supported by grants from the Chinese Academy of Sciences(KSCX2-EW-R-12,KSCX2-EW-J-23)the National Natural Science Foundation of China(81171294)Shanghai Science&Technology Development Foundation(12140904200).
文摘Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1)body weight,(2)core body temperature and rhythm,(3)diet metabolism,(4)locomotor rhythm,(5)electroencephalogram,(6)glycometabolism and(7)serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that(a)the core body temperature of the tree shrew was 39.59±0.05°C,which was higher than that of rats and macaques;(b)Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30;(c)Compared with rats,tree shrews had poor carbohydrate metabolism ability;and(d)Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.
基金supported by the Breakthrough Project of Strategic Priority Program of the Chinese Academy of Sciences(XDB13000000)
文摘As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained （conception rate=74%）. Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.
基金Laboratory Animal Science of PLA,Grant/Award Number:SYDW[2014]-0009The National Science and Technology Support Program,Grant/Award Number:2011BAI15B01,2014BAI01B01
文摘Backgroud: Current understanding of injury and regeneration of islet β-cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of primates, and has been widely used in animal experimentation. However, there are few reports on islet cell composition and regeneration of β-cells in tree shrews.Methods: In this study, we examined the changes in islet cell composition and regeneration of β-cells after streptozotocin(STZ) treatment in tree shrews compared with Sprague-Dawley rats. Injury and regeneration of islet β-cells were observed using hematoxylin and eosin(HE) staining and immunohistochemical staining for insulin, glucagon, somatostatin and PDX-1.Results: Our data showed that in rats islet injury was most obvious on day 3 after injection, and islet morphologies were significantly restored by day 21. Regeneration of islet β-cells was very pronounced in rats, and mainly involved regeneration of centro-acinar cells and transformation of extra-islet ductal cells. In tree shrews, the regeneration of islet β-cells was not as significant. On days 3 and 7, only scattered regenerated cells were observed in the remaining islets. Further, no regeneration of centro-acinar cells was observed.Conclusion: The results suggest that the repair mechanism of islet β-cells in tree shrews is similar to that of humans.
基金This study was supported by a grant from the National Natural Science Foundation of China(No. 39260033)and a grant from Guangxi Science Foundation, China (No. 0143058).
文摘OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.
基金supported by the STI2030-Major Projects(2022ZD0205202)Anhui Provincial Natural Science Foundation(2408085Y043)National Natural Science Foundation of China(82471540,32030046,32200798)。
文摘Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial architecture.However,the anatomical distribution and morphological characteristics of astrocytes in the tree shrew brain remain poorly characterized.In this study,glial fibrillary acidic protein(GFAP)immunofluorescence was employed to systematically examine the spatial distribution and morphology of astrocytes in the whole brain of tree shrews.Notably,GFAP-immunoreactive(ir)astrocytes were detected throughout the telencephalon,diencephalon,mesencephalon,metencephalon,and myelencephalon.Distinct laminar distribution was evident in regions such as the main olfactory bulb and hippocampus.Semi-quantitative comparisons revealed significant regional differences in astrocyte density between tree shrews and mice,encompassing the main olfactory bulb,accessory olfactory bulb,olfactory tubercle,cortex,hippocampus,cortical amygdaloid nucleus,hypothalamus,thalamus,superior colliculus,interpeduncular nucleus,median raphe nucleus,and parabrachial nucleus.Compared to mice,tree shrews exhibited higher astrocyte density with increased morphological complexity in the posterior hypothalamic nucleus,dorsomedial hypothalamic nucleus,ventromedial hypothalamic nucleus,and periaqueductal gray,but lower density with greater morphological complexity in the hippocampus and substantia nigra.In the paraventricular hypothalamic nucleus and lateral hypothalamic area,GFAP-ir astrocytes displayed comparable densities between tree shrews and mice but exhibited region-specific differences in morphological complexity.This study provides the first brain-wide mapping of GFAP-ir astrocytes in tree shrews,revealing marked interspecies differences in their distribution and morphology,and establishing a neuroanatomical framework for understanding astrocyte involvement in diverse physiological and behavioral functions.
基金the grants from Specialized Research Fund for the Doctoral Program of Higher Education(No.20050678008)National Natural Science Foundation of China (No.3066005).
文摘Background It has been known that platelet activating factor receptors （PAFR） may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B （GB） possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment. Methods Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow （rCBF, using ^99rnTc tracer technique ）, the brain water content （specific gravimetric method）, PAFR （3H-labelled PAF assay）, the respiratory control rate （RCR）, the phosphorus-oxygen （P/O） ratio of mitochondrial respiration （Clark oxygen electrode）, mitochonddal permeability transition （MPT） pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups （the ischemia group vs the sham group, and the ischemia group vs the GB group）. Results There were high affinity and low affinity sites for PAFR on the tree threws＇ brain cell membranes. The varying-affinity PAFR binding sites, the respiration state Ⅲ, the state Ⅳ, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly （respectively, P〈0.01 and P〈0.05）, but the water content increased （P〈0.01） in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB （5 mg/kg i.v.） 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated （P〈0.01） at 24h after cerebral ischemia. There were significant differences between the ischemJa group and sham group （P〈0.01）. In GB treated isolated neurons＇ mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed. Conclusions The activation of the PAFR may play an important role in the inhibition of the mitochondrial respiration and the induction of neuronal damage after cerebral thrombosis; however, GB possesses neuroprotective effects by improving mitochondrial metabolism.
基金We thank Tingting Zhang for her suggestion in the discussion and Dr Junxiao Xu for his help with computer language.We thank Professor Liang Liu at Delaware State University for his help in species tree reconstruction.We also sincerely appreciate the thoughtful and constructive comments from Szucsich Nikolaus and the other anonymous reviewer.This research was supported by the major project of the Natural Science Foundation of the Jiangsu Higher Education Institutions of Jiangsu Province,China(07KJA18016)(to G.Y.)the National Key Technology R&D Program of China(2013BAD03B02)the National Natural Science Foundation of China(No.31270420)(to M.L.).
文摘The well-accepted Euarchonta grandorder is a pruned version of Archonta nested within the Euarchontoglires(or Supraprimates)clade.At present,it includes tree shrews(Scandentia),flying lemurs(Dermoptera)and primates(Primates).Here,a phylogenomic dataset containing 1912 exons from 22 representative mammals was compiled to investigate the phylogenetic relationships within this group.Phylogenetic analyses and hypothesis testing suggested that tree shrews can be classified as a sister group to Primates or to Glires or even as a basal clade within Euarchontoglires.Further analyses of both modified and original previously published datasets found that the phylogenetic position of tree shrews is unstable.We also found that two of three exonic indels reported as synapomorphies of Euarchonta in a previous study do not unambiguously support the monophyly of such a clade.Therefore,the monophyly of both Euarchonta and Sundatheria(Dermoptera+Scandentia)are suspect.Molecular dating and divergence rate analyses suggested that the ancestor of Euarchontoglires experienced a rapid divergence,which may cause the unresolved position of tree shrews even using the whole genomic data.
