The temporal pole(TP),one of the most expanded cortical regions in humans relative to other primates,plays a crucial role in human language processing.It is also one of the most structurally and functionally asymmetri...The temporal pole(TP),one of the most expanded cortical regions in humans relative to other primates,plays a crucial role in human language processing.It is also one of the most structurally and functionally asymmetric regions.However,whether the functional architecture of the TP is shared by humans and macaques is an open question.We used spectral clustering algorithms to define a cross-species fine-grained TP atlas with different anatomical connectivity patterns.We identified three similar subregions,two ventral and one dorsal,within the TP in both humans and macaques.The parcellation scheme for the TP was validated using functional gradient mapping,anatomical connectivity and resting-state functional connectivity pattern analysis,and functional characterization.Furthermore,in conjunction with the Allen Human Brain Atlas,we revealed the molecular basis for the functional connectivity patterns of each human TP subregion.In addition,we compared the hemispheric asymmetry in mean gray matter volume,anatomical connectivity fingerprints,and whole brain functional connectivity patterns to reveal the evolutionary differences in the TP and found different asymmetric patterns between humans and macaques.In conclusion,our findings reveal that the asymmetry in structure and connectivity may underpin the hemispheric functional specialization of the brain and provide a novel insight into understanding the evolutionary origin of the TP.展开更多
Continual learning fault diagnosis(CLFD)has gained growing interest in mechanical systems for its ability to accumulate and transfer knowledge in dynamic fault diagnosis scenarios.However,existing CLFD methods typical...Continual learning fault diagnosis(CLFD)has gained growing interest in mechanical systems for its ability to accumulate and transfer knowledge in dynamic fault diagnosis scenarios.However,existing CLFD methods typically assume balanced task distributions,neglecting the long-tailed nature of real-world fault occurrences,where certain faults dominate while others are rare.Due to the long-tailed distribution among different me-chanical conditions,excessive attention has been focused on the dominant type,leading to performance de-gradation in rarer types.In this paper,decoupling incremental classifier and representation learning(DICRL)is proposed to address the dual challenges of catastrophic forgetting introduced by incremental tasks and the bias in long-tailed CLFD(LT-CLFD).The core innovation lies in the structural decoupling of incremental classifier learning and representation learning.An instance-balanced sampling strategy is employed to learn more dis-criminative deep representations from the exemplars selected by the herding algorithm and new data.Then,the previous classifiers are frozen to prevent damage to representation learning during backward propagation.Cosine normalization classifier with learnable weight scaling is trained using a class-balanced sampling strategy to enhance classification accuracy.Experimental results demonstrate that DICRL outperforms existing continual learning methods across multiple benchmarks,demonstrating superior performance and robustness in both LT-CLFD and conventional CLFD.DICRL effectively tackles both catastrophic forgetting and long-tailed distribution in CLFD,enabling more reliable fault diagnosis in industrial applications.展开更多
Accurate macaque paternity identification is of great significance in various fields,yet relevant research remains scarce.Our study aimed to screen effective microsatellite markers for macaque paternity testing.Initia...Accurate macaque paternity identification is of great significance in various fields,yet relevant research remains scarce.Our study aimed to screen effective microsatellite markers for macaque paternity testing.Initially,300 microsatellite markers were randomly selected from the genome of the crab-eating macaque(Macaca fascicularis),and 12 highly polymorphic tetra-nucleotide repeat markers were identified.These markers'genetic parameters and exclusion probabilities in both crab-eating and rhesus macaque(Macaca mulatta)populations were calculated,meeting the paternity testing requirements for both species.To validate the markers,16 crab-eating macaque and 10 rhesus macaque families with known pedigrees were randomly chosen for testing.The genotypes of the 12 markers in the macaques'offspring could be traced back to their parents,confirming the accuracy and applicability of the marker combination for paternity identification in both macaque species.展开更多
Rhesus macaques(Macaca mulatta)have demonstrated a potent capability of adapting to human-disturbed environment.In China,they have become popular attractions in ecotourism areas and receive substantial food from touri...Rhesus macaques(Macaca mulatta)have demonstrated a potent capability of adapting to human-disturbed environment.In China,they have become popular attractions in ecotourism areas and receive substantial food from tourists,resulting in local booming populations.Previous studies have highlighted human-macaque conflicts and yet ignored their impact on local natural ecosystems.Through reviewing previous researches,we summarized the contributing factors to the thriving populations of rhesus macaque and expounded upon the potential impacts of them on other local organisms.Booming populations of rhesus macaque caused by provisioning could present potential risks to local plant and animal community through lesser seed dispersal and greater predation and competition pressures on other sympatric species,ultimately impacting the diversity and stability of local ecosystems.Thus,it is imperative to draft the relevant laws to strictly control human provisioning for wild rhesus macaques and conduct further studies to elucidate their interspecies relationships.And a higher priority should be devoted to monitoring these potentially overabundant populations and formulating optimal management strategies to achieve harmonious coexistence between humans and rhesus macaques.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
Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features.Using single-nucleus RNA sequencing,we identified cell-specific transcriptomic changes...Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features.Using single-nucleus RNA sequencing,we identified cell-specific transcriptomic changes in the nucleus accumbens(NAc),particularly in astrocytes,of adolescent macaques exhibiting depressive-like behaviors.The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques,while FKBP5 levels increased in glial cells.Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons(MSNs)and subtypes of astrocytes.Communication pathways between astrocytes and D1/D2-MSNs were also disrupted,involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4.Bulk transcriptomic and proteomic analyses corroborated these findings,and FKBP5 upregulation was confirmed by qRT-PCR,western blotting,and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress.Our results highlight the specific roles of different cell types in adolescent depression in the NAc,offering potential targets for new antidepressant therapies.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
Zona pellucida glycoprotein-1(ZP1)is essential for maintaining oocyte structural integrity and facilitating fertilization.Mutations in ZP1 are strongly associated with primary infertility disorders such as fertilizati...Zona pellucida glycoprotein-1(ZP1)is essential for maintaining oocyte structural integrity and facilitating fertilization.Mutations in ZP1 are strongly associated with primary infertility disorders such as fertilization failure and empty follicle syndrome;however,the absence of accurate experimental models has hindered mechanistic understanding and obscured the etiological basis of ZP1-related infertility.In this study,CRISPR/Cas9-mediated genome editing was employed to generate two ZP1-edited cynomolgus macaques(Macaca fascicularis),designated#ZP1-1(male)and#ZP1-2(female).Following sexual maturation,oocytes retrieved from#ZP1-2 through superovulation exhibited a marked increase in zona pellucida-deficient oocytes and a significant reduction in maturation rates compared to controls.Integrated analyses,including immunofluorescence staining,transmission electron microscopy,transcriptomic profiling of oocytes,and histopathological examination of ovarian tissue,revealed disrupted folliculogenesis and oocyte anomalies consistent with phenotypes observed in human empty follicle syndrome.These findings establish the ZP1-knockout cynomolgus macaque as the first non-human primate model of ZP1-related infertility,providing a valuable platform for elucidating disease mechanisms and informing the development of targeted interventions for infertility arising from ZP gene mutations.展开更多
Reach-to-grasp movements require integrating information on both object location and grip type,but how these elements are planned and to what extent they interact remains unclear.We designed a new experimental paradig...Reach-to-grasp movements require integrating information on both object location and grip type,but how these elements are planned and to what extent they interact remains unclear.We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays,requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures.Neural activity in the dorsal premotor cortex(PMd)revealed that reach and grasp were similarly represented yet not independent.Upon receiving the second cue,the PMd continued encoding the first,but over half of the neurons displayed incongruent modulations:enhanced,attenuated,or even reversed.Population-level analysis showed significant changes in encoding structure,forming distinct neural patterns.Leveraging canonical correlation analysis,we identified a shared subspace preserving the initial cue’s encoding,contributed by both congruent and incongruent neurons.Together,these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd,providing insights into potential applications for brain–machine interfaces.展开更多
Infant-care behavior,a range of caring behaviors by parental or alloparental individuals towards infants unable to live independently,plays asignifcant role in the survival of infants and the continuation of the speci...Infant-care behavior,a range of caring behaviors by parental or alloparental individuals towards infants unable to live independently,plays asignifcant role in the survival of infants and the continuation of the species in non-human primates.During a behavioral ecological study ofTaihangshan macaques,we observed 2 cases of infant adoptions by unrelated adult females.In case 1,a multiparous female adopted a lostinfant from a neighboring group,with the infant being snatched back by her biological mother 35 days after the adoption.This is the frst report ofcross-group adoption in Macaca.In case 2,a nulliparous adult female,who had been once adopted by her elder sister,adopted an orphan fromher group for 36 days.We describe the details of adoptions in Taihangshan macaques and explore possible reasons for adoptions to contributeto understanding the evolution of infant-care behavior and altruistic behavior of adoption in primates.展开更多
Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning f...Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning framework enhanced by knowledge graphs.Methods We developed Agent-GNN,a three-stage decoupled learning framework,and validated it on the Traditional Chinese Medicine Syndrome Diagnosis(TCM-SD)dataset containing 54152 clinical records across 148 syndrome categories.First,we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system.Second,we proposed a Functional Patient Profiling(FPP)method that utilizes large language models(LLMs)combined with Graph Retrieval-Augmented Generation(RAG)to extract structured symptom-etiology-pathogenesis subgraphs from medical records.Third,we employed heterogeneous graph neural networks to learn structured combination patterns explicitly.We compared our method against multiple baselines including BERT,ZY-BERT,ZY-BERT+Know,GAT,and GPT-4 Few-shot,using macro-F1 score as the primary evaluation metric.Additionally,ablation experiments were conducted to validate the contribution of each key component to model performance.Results Agent-GNN achieved an overall macro-F1 score of 72.4%,representing an 8.7 percentage points improvement over ZY-BERT+Know(63.7%),the strongest baseline among traditional methods.For long-tail syndromes with fewer than 10 samples,Agent-GNN reached a macro-F1 score of 58.6%,compared with 39.3%for ZY-BERT+Know and 41.2%for GPT-4 Few-shot,representing relative improvements of 49.2%and 42.2%,respectively.Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance.Conclusion This study proposes Agent-GNN,a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation.By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs,our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.展开更多
Although seasonal breeding has been documented in many non-human primates, it is not clear whether sexual behaviors show seasonal variation among male individuals. To test this hypothesis, the focal animal sampling me...Although seasonal breeding has been documented in many non-human primates, it is not clear whether sexual behaviors show seasonal variation among male individuals. To test this hypothesis, the focal animal sampling method and continuous recording were used to investigate seasonal variation and synchronization of sexual behaviors in five male Tibetan macaques （Macaca thibetana） at Mt. Huangshan from Oct 2005 to Sept 2006. Both copulatory and sexually motivated behaviors （i.e., sexual chase, grimace, and sexual-inspection）, which were significantly higher in the mating season than non-mating season. Furthermore, seasonal variations of sexual behaviors, including copulatory and sexually motivated behaviors, were synchronized among males. The results shed light on sexual competition and tactics for reproductive success of male M. thibetana and other non-human primates with seasonal breeding.展开更多
Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in...Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.展开更多
The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper an...The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques （Macaca leonina） are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.展开更多
The northem pig-tailed macaque （NPM, Macaca leonina） has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3...The northem pig-tailed macaque （NPM, Macaca leonina） has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age （P〉0.05）, while serum IgG levels increased progressively with age （r=0.202; P=0.045）. Serum IgG, IgA, IgM and C3 levels were higher in females than in males （P〈0.05）. Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 （r=0.700; P〈0.0001）. This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.展开更多
In some non-human primates, infants function as a social tool that can bridge relationships among group members. Infants are a desired commodity for group members, and mothers control access to them. The biological ma...In some non-human primates, infants function as a social tool that can bridge relationships among group members. Infants are a desired commodity for group members, and mothers control access to them. The biological market theory suggests that grooming is widespread and represents a commodity that can be exchanged for infant handling. As a limited resource, however, the extent to which infants are interchanged between mothers(females with an infant) and non-mothers(potential handlers,females without an infant) remains unclear. In this study, we collected behavioral data to investigate the relationship between grooming and infant handling in free-ranging Tibetan macaques(Macaca thibetana)at Mt. Huangshan, China. Our results showed that females with infants received more grooming than females without infants. After her infant was handled,mother females received more grooming than they did during daily grooming interactions. However, with the increasing number of infants within the social group, both the grooming that mothers received and the grooming that non-mothers invested for handling infants decreased. We also found that non-mothers invested more time in grooming to gain access to younger infants than older infants. Our results provide evidence that infants are social commodities for both mother and non-mother females. Mothers use infants for obtain grooming and non-mothers use grooming to gain access to infants. The current study implies a bidirectional and complex interchange pattern between grooming and infant handling to compensate for the dyadic grooming disparity in non-human primates.展开更多
Rhesus macaques(Macaca mulatta) and cynomolgus macaques(Macaca fascicularis) are frequently used in establishing animal models for human diseases. To determine the differences in gut microbiota between these species, ...Rhesus macaques(Macaca mulatta) and cynomolgus macaques(Macaca fascicularis) are frequently used in establishing animal models for human diseases. To determine the differences in gut microbiota between these species, rectal swabs from 20 rhesus macaques and 21 cynomolgus macaques were collected, and the microbial composition was examined by deep sequencing of the 16 S rR NA gene. We found that the rectal microbiota of cynomolgus macaques exhibited significantly higher alpha diversity than that of rhesus macaques, although the observed number of operational taxonomic units(OTUs) was almost the same. The dominant taxa at both the phylum and genus levels were similar between the two species, although the relative abundances of these dominant taxa were significantly different between them. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt) showed significant differences in the functional components between the microbiota of the two species, in particular the lipopolysaccharide(LPS) synthesis proteins. The above data indicated significant differences in microbial composition and function between these two closely related macaque species, which should be taken into consideration in the future selection of these animals for disease models.展开更多
The northern pig-tailed macaque （Macaca leonina） has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus...The northern pig-tailed macaque （Macaca leonina） has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 （HIV-1）, which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-INL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of v/f-substituted HIV-1 （HSIV） in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-lsv chimeras, two HIV-1Ni.4-3-derived viruses encoding the viral infectivity factor （Vif） protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.展开更多
There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been cruci...There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface;however,studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models.Here,we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status.Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment.Furthermore,the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment,and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed.In addition to inducing aberrant morphology of small intestinal villi,the depletion of gut commensal bacteria led to increased proportions of CD3+T,CD4+T,and CD16+NK cells in peripheral blood mononuclear cells(PBMCs),but decreased numbers of Treg and CD20+B cells.The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes,including IL-13,VCAM1,and LGR4.展开更多
Objective To develop a model of SHIV-KB9/Chinese origin rhesus （Ch Rh） macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus （Ind Rh） macaq...Objective To develop a model of SHIV-KB9/Chinese origin rhesus （Ch Rh） macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus （Ind Rh） macaques. Methods Seven mamu-A＊01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CDS, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4^＋ T cells were associated with humoral responses. Otherwise, the viral genetic distances （divergence, diversity） were larger in animals （M419, M425） with their CD4^＋ T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.展开更多
基金supported by the Yunnan Fundamental Research Projects(202501AV070005 and 202201BE070001-004).
文摘The temporal pole(TP),one of the most expanded cortical regions in humans relative to other primates,plays a crucial role in human language processing.It is also one of the most structurally and functionally asymmetric regions.However,whether the functional architecture of the TP is shared by humans and macaques is an open question.We used spectral clustering algorithms to define a cross-species fine-grained TP atlas with different anatomical connectivity patterns.We identified three similar subregions,two ventral and one dorsal,within the TP in both humans and macaques.The parcellation scheme for the TP was validated using functional gradient mapping,anatomical connectivity and resting-state functional connectivity pattern analysis,and functional characterization.Furthermore,in conjunction with the Allen Human Brain Atlas,we revealed the molecular basis for the functional connectivity patterns of each human TP subregion.In addition,we compared the hemispheric asymmetry in mean gray matter volume,anatomical connectivity fingerprints,and whole brain functional connectivity patterns to reveal the evolutionary differences in the TP and found different asymmetric patterns between humans and macaques.In conclusion,our findings reveal that the asymmetry in structure and connectivity may underpin the hemispheric functional specialization of the brain and provide a novel insight into understanding the evolutionary origin of the TP.
基金Supported by National Natural Science Foundation of China(Grant No.52272440)Suzhou Science Foundation(Grant Nos.SYG202323,ZXL2022027).
文摘Continual learning fault diagnosis(CLFD)has gained growing interest in mechanical systems for its ability to accumulate and transfer knowledge in dynamic fault diagnosis scenarios.However,existing CLFD methods typically assume balanced task distributions,neglecting the long-tailed nature of real-world fault occurrences,where certain faults dominate while others are rare.Due to the long-tailed distribution among different me-chanical conditions,excessive attention has been focused on the dominant type,leading to performance de-gradation in rarer types.In this paper,decoupling incremental classifier and representation learning(DICRL)is proposed to address the dual challenges of catastrophic forgetting introduced by incremental tasks and the bias in long-tailed CLFD(LT-CLFD).The core innovation lies in the structural decoupling of incremental classifier learning and representation learning.An instance-balanced sampling strategy is employed to learn more dis-criminative deep representations from the exemplars selected by the herding algorithm and new data.Then,the previous classifiers are frozen to prevent damage to representation learning during backward propagation.Cosine normalization classifier with learnable weight scaling is trained using a class-balanced sampling strategy to enhance classification accuracy.Experimental results demonstrate that DICRL outperforms existing continual learning methods across multiple benchmarks,demonstrating superior performance and robustness in both LT-CLFD and conventional CLFD.DICRL effectively tackles both catastrophic forgetting and long-tailed distribution in CLFD,enabling more reliable fault diagnosis in industrial applications.
基金Nanhu Laboratory Self-Initiated Research Project,Grant/Award Number:NSS2023A00001-2。
文摘Accurate macaque paternity identification is of great significance in various fields,yet relevant research remains scarce.Our study aimed to screen effective microsatellite markers for macaque paternity testing.Initially,300 microsatellite markers were randomly selected from the genome of the crab-eating macaque(Macaca fascicularis),and 12 highly polymorphic tetra-nucleotide repeat markers were identified.These markers'genetic parameters and exclusion probabilities in both crab-eating and rhesus macaque(Macaca mulatta)populations were calculated,meeting the paternity testing requirements for both species.To validate the markers,16 crab-eating macaque and 10 rhesus macaque families with known pedigrees were randomly chosen for testing.The genotypes of the 12 markers in the macaques'offspring could be traced back to their parents,confirming the accuracy and applicability of the marker combination for paternity identification in both macaque species.
基金Fundamental Research Funds for the Central Universities,Sun Yat-sen University(23lgzy002)Forestry Administration of Guangdong Province(33000-42090019)+1 种基金Shenzhen Park Service(33000-71020177)Neilingding-Futian National Nature Reserve(33000-71020200)。
文摘Rhesus macaques(Macaca mulatta)have demonstrated a potent capability of adapting to human-disturbed environment.In China,they have become popular attractions in ecotourism areas and receive substantial food from tourists,resulting in local booming populations.Previous studies have highlighted human-macaque conflicts and yet ignored their impact on local natural ecosystems.Through reviewing previous researches,we summarized the contributing factors to the thriving populations of rhesus macaque and expounded upon the potential impacts of them on other local organisms.Booming populations of rhesus macaque caused by provisioning could present potential risks to local plant and animal community through lesser seed dispersal and greater predation and competition pressures on other sympatric species,ultimately impacting the diversity and stability of local ecosystems.Thus,it is imperative to draft the relevant laws to strictly control human provisioning for wild rhesus macaques and conduct further studies to elucidate their interspecies relationships.And a higher priority should be devoted to monitoring these potentially overabundant populations and formulating optimal management strategies to achieve harmonious coexistence between humans and rhesus macaques.
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 STI2030-Major Projects(2022ZD0212900)the Joint Project of Chongqing Municipal Science and Technology Bureau and Chongqing Health Commission(2023CCXM003)+4 种基金the National Key Research and Development Program of China(2017YFA0505700)the National Natural Science Foundation of China(82271565 and 82301714)the China Postdoctoral Science Foundation(2023TQ0398,GZB20230916,2023MD734124)the Natural Science Foundation of Chongqing,China(CSTB2023NSCQ-BHX0106)the Postdoctoral Innovation Talents Support Program of Chongqing,China(2208013341918508).
文摘Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features.Using single-nucleus RNA sequencing,we identified cell-specific transcriptomic changes in the nucleus accumbens(NAc),particularly in astrocytes,of adolescent macaques exhibiting depressive-like behaviors.The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques,while FKBP5 levels increased in glial cells.Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons(MSNs)and subtypes of astrocytes.Communication pathways between astrocytes and D1/D2-MSNs were also disrupted,involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4.Bulk transcriptomic and proteomic analyses corroborated these findings,and FKBP5 upregulation was confirmed by qRT-PCR,western blotting,and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress.Our results highlight the specific roles of different cell types in adolescent depression in the NAc,offering potential targets for new antidepressant therapies.
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.
基金supported by the National Key R&D Program of China(2018YFA0801404,2023YFC3403400)National Natural Science Foundation of China(81941006)+2 种基金Guangdong Special Support Program(2019BT02Y276)Specific University Discipline Construction Project(2023B10564003)Guangdong Natural Science Funds for Distinguished Young Scholars(2021B1515020079)。
文摘Zona pellucida glycoprotein-1(ZP1)is essential for maintaining oocyte structural integrity and facilitating fertilization.Mutations in ZP1 are strongly associated with primary infertility disorders such as fertilization failure and empty follicle syndrome;however,the absence of accurate experimental models has hindered mechanistic understanding and obscured the etiological basis of ZP1-related infertility.In this study,CRISPR/Cas9-mediated genome editing was employed to generate two ZP1-edited cynomolgus macaques(Macaca fascicularis),designated#ZP1-1(male)and#ZP1-2(female).Following sexual maturation,oocytes retrieved from#ZP1-2 through superovulation exhibited a marked increase in zona pellucida-deficient oocytes and a significant reduction in maturation rates compared to controls.Integrated analyses,including immunofluorescence staining,transmission electron microscopy,transcriptomic profiling of oocytes,and histopathological examination of ovarian tissue,revealed disrupted folliculogenesis and oocyte anomalies consistent with phenotypes observed in human empty follicle syndrome.These findings establish the ZP1-knockout cynomolgus macaque as the first non-human primate model of ZP1-related infertility,providing a valuable platform for elucidating disease mechanisms and informing the development of targeted interventions for infertility arising from ZP gene mutations.
基金supported by STI 2030-Major Projects(2022ZD0208903)the National Natural Science Foundation of China(62336007)+3 种基金the Natural Science Foundation of Shandong Province(ZR2024QH582)the Pioneer R&D Program of Zhejiang Province(2024C03001)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-002)the Fundamental Research Funds for the Central Universities(2024ZFJH01-01).
文摘Reach-to-grasp movements require integrating information on both object location and grip type,but how these elements are planned and to what extent they interact remains unclear.We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays,requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures.Neural activity in the dorsal premotor cortex(PMd)revealed that reach and grasp were similarly represented yet not independent.Upon receiving the second cue,the PMd continued encoding the first,but over half of the neurons displayed incongruent modulations:enhanced,attenuated,or even reversed.Population-level analysis showed significant changes in encoding structure,forming distinct neural patterns.Leveraging canonical correlation analysis,we identified a shared subspace preserving the initial cue’s encoding,contributed by both congruent and incongruent neurons.Together,these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd,providing insights into potential applications for brain–machine interfaces.
基金fnancially supported by the National Natural Science Foundation of China(No.32070446).
文摘Infant-care behavior,a range of caring behaviors by parental or alloparental individuals towards infants unable to live independently,plays asignifcant role in the survival of infants and the continuation of the species in non-human primates.During a behavioral ecological study ofTaihangshan macaques,we observed 2 cases of infant adoptions by unrelated adult females.In case 1,a multiparous female adopted a lostinfant from a neighboring group,with the infant being snatched back by her biological mother 35 days after the adoption.This is the frst report ofcross-group adoption in Macaca.In case 2,a nulliparous adult female,who had been once adopted by her elder sister,adopted an orphan fromher group for 36 days.We describe the details of adoptions in Taihangshan macaques and explore possible reasons for adoptions to contributeto understanding the evolution of infant-care behavior and altruistic behavior of adoption in primates.
基金Sichuan TCM Culture Coordinated Development Research Center Project(2023XT131)National Key Science and Technology Project of China(2023ZD0509405)National Natural Science Foundation of China(82174236).
文摘Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning framework enhanced by knowledge graphs.Methods We developed Agent-GNN,a three-stage decoupled learning framework,and validated it on the Traditional Chinese Medicine Syndrome Diagnosis(TCM-SD)dataset containing 54152 clinical records across 148 syndrome categories.First,we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system.Second,we proposed a Functional Patient Profiling(FPP)method that utilizes large language models(LLMs)combined with Graph Retrieval-Augmented Generation(RAG)to extract structured symptom-etiology-pathogenesis subgraphs from medical records.Third,we employed heterogeneous graph neural networks to learn structured combination patterns explicitly.We compared our method against multiple baselines including BERT,ZY-BERT,ZY-BERT+Know,GAT,and GPT-4 Few-shot,using macro-F1 score as the primary evaluation metric.Additionally,ablation experiments were conducted to validate the contribution of each key component to model performance.Results Agent-GNN achieved an overall macro-F1 score of 72.4%,representing an 8.7 percentage points improvement over ZY-BERT+Know(63.7%),the strongest baseline among traditional methods.For long-tail syndromes with fewer than 10 samples,Agent-GNN reached a macro-F1 score of 58.6%,compared with 39.3%for ZY-BERT+Know and 41.2%for GPT-4 Few-shot,representing relative improvements of 49.2%and 42.2%,respectively.Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance.Conclusion This study proposes Agent-GNN,a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation.By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs,our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.
文摘Although seasonal breeding has been documented in many non-human primates, it is not clear whether sexual behaviors show seasonal variation among male individuals. To test this hypothesis, the focal animal sampling method and continuous recording were used to investigate seasonal variation and synchronization of sexual behaviors in five male Tibetan macaques （Macaca thibetana） at Mt. Huangshan from Oct 2005 to Sept 2006. Both copulatory and sexually motivated behaviors （i.e., sexual chase, grimace, and sexual-inspection）, which were significantly higher in the mating season than non-mating season. Furthermore, seasonal variations of sexual behaviors, including copulatory and sexually motivated behaviors, were synchronized among males. The results shed light on sexual competition and tactics for reproductive success of male M. thibetana and other non-human primates with seasonal breeding.
基金partly supported by grants from the National Natural Science Foundation of China(U1802284 81471620,81671627,81771770,81571606)+1 种基金13th Five-Year Key Scientific and Technological Program of China(2017ZX10304402-002-004,2017ZX10202102-001-005,2018ZX10301101-002-003,2018ZX10301406-003)Knowledge Innovation Program of the Chinese Academy of Sciences(ZDRW-ZS-2016-4)
文摘Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.
基金supported in part by the Key Scientific and Technological Program of China(2012ZX10001-0072013ZX10001-002)+5 种基金the National Basic Research Program of China(2012CBA01305)the National Natural Science Foundation of China(8117287681273251U1202228)the Knowledge Innovation Program of CAS(KSCX2-EW-R-13KJZD-EW-L10-02)
文摘The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques （Macaca leonina） are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.
基金Foundation items： This work was supported by the National Natural Science Foundation of China （81172876, U0832601, 81273251, U1202228） the National Special Science Research Program of China （2012CBA01305） the National Science and Technology Major Project （2013ZX10001-002, 2012ZX10001-007） and the Knowledge Innovation Program of CAS （KSCX2-EW-R-13）.
文摘The northem pig-tailed macaque （NPM, Macaca leonina） has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age （P〉0.05）, while serum IgG levels increased progressively with age （r=0.202; P=0.045）. Serum IgG, IgA, IgM and C3 levels were higher in females than in males （P〈0.05）. Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 （r=0.700; P〈0.0001）. This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.
基金supported in part by grants from the National Natural Science Foundation of China(31772475 31672307+1 种基金31401981 31372215)
文摘In some non-human primates, infants function as a social tool that can bridge relationships among group members. Infants are a desired commodity for group members, and mothers control access to them. The biological market theory suggests that grooming is widespread and represents a commodity that can be exchanged for infant handling. As a limited resource, however, the extent to which infants are interchanged between mothers(females with an infant) and non-mothers(potential handlers,females without an infant) remains unclear. In this study, we collected behavioral data to investigate the relationship between grooming and infant handling in free-ranging Tibetan macaques(Macaca thibetana)at Mt. Huangshan, China. Our results showed that females with infants received more grooming than females without infants. After her infant was handled,mother females received more grooming than they did during daily grooming interactions. However, with the increasing number of infants within the social group, both the grooming that mothers received and the grooming that non-mothers invested for handling infants decreased. We also found that non-mothers invested more time in grooming to gain access to younger infants than older infants. Our results provide evidence that infants are social commodities for both mother and non-mother females. Mothers use infants for obtain grooming and non-mothers use grooming to gain access to infants. The current study implies a bidirectional and complex interchange pattern between grooming and infant handling to compensate for the dyadic grooming disparity in non-human primates.
基金supported by the National Natural Science Foundation of China(81571607)Beijing Natural Science Foundation(7162136)Ministry of Science and Technology(2017ZX10202102003005,2015BAI08B03)of China
文摘Rhesus macaques(Macaca mulatta) and cynomolgus macaques(Macaca fascicularis) are frequently used in establishing animal models for human diseases. To determine the differences in gut microbiota between these species, rectal swabs from 20 rhesus macaques and 21 cynomolgus macaques were collected, and the microbial composition was examined by deep sequencing of the 16 S rR NA gene. We found that the rectal microbiota of cynomolgus macaques exhibited significantly higher alpha diversity than that of rhesus macaques, although the observed number of operational taxonomic units(OTUs) was almost the same. The dominant taxa at both the phylum and genus levels were similar between the two species, although the relative abundances of these dominant taxa were significantly different between them. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt) showed significant differences in the functional components between the microbiota of the two species, in particular the lipopolysaccharide(LPS) synthesis proteins. The above data indicated significant differences in microbial composition and function between these two closely related macaque species, which should be taken into consideration in the future selection of these animals for disease models.
基金Foundation items： This work was supported by the National Basic Research Program （2012CBA01305） the National Natural Science Foundation of China （81172876, U0832601, 81273251 and U 1202228） the Knowledge Innovation Program of CAS （KSCX2-EW-R-13, Y206A- 71181）, and the Key Scientific and Technological Program of China （2012ZX10001-007, 2013ZX10001-002）. Acknowledgements： We thank Prof. Guang-Xia GAO （Institute of Biophysics, Chinese Academy of Sciences） for kindly providing HSIV proviral plasmids.We also thank Long-Bao LV, Gui LI and Dong- Ti HUANG of Kunming Primate Research Center for their assistance in obtaining blood samples from northem pig-tailed macaques （M. leonina） and Chinese rhesus macaques.
文摘The northern pig-tailed macaque （Macaca leonina） has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 （HIV-1）, which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-INL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of v/f-substituted HIV-1 （HSIV） in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-lsv chimeras, two HIV-1Ni.4-3-derived viruses encoding the viral infectivity factor （Vif） protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2016-I2M-1-014)
文摘There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface;however,studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models.Here,we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status.Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment.Furthermore,the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment,and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed.In addition to inducing aberrant morphology of small intestinal villi,the depletion of gut commensal bacteria led to increased proportions of CD3+T,CD4+T,and CD16+NK cells in peripheral blood mononuclear cells(PBMCs),but decreased numbers of Treg and CD20+B cells.The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes,including IL-13,VCAM1,and LGR4.
文摘Objective To develop a model of SHIV-KB9/Chinese origin rhesus （Ch Rh） macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus （Ind Rh） macaques. Methods Seven mamu-A＊01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CDS, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4^＋ T cells were associated with humoral responses. Otherwise, the viral genetic distances （divergence, diversity） were larger in animals （M419, M425） with their CD4^＋ T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.
