The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of ef...The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.展开更多
Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve ...Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve transplantation result in substantial and irreversible visual loss in patients with TON.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional ...Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional activity through the conversion of 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).While DNA methylation is hypothesized to play an essential role in shaping brain identity by influencing gene expression patterns,its direct contribution,especially in primates,remains largely unexplored.This study examined DNA methylation landscapes and transcriptional profiles across four brain regions,including the cortex,cerebellum,striatum,and hippocampus,using samples from 12 rhesus monkeys.The cerebellum exhibited distinct epigenetic and transcriptional signatures,with differentially methylated regions(DMRs)significantly enriched in metabolic pathways.Notably,genes harboring clustered differentially hydroxymethylated regions(DhMRs)overlapped with those implicated in schizophrenia.Moreover,5mC located1 kb upstream of the ATG start codon was correlated with gene expression and exhibited region-specific associations with 5hmC.These findings provide insights into the coordinated regulation of cerebellum-specific 5mC and5hmC,highlighting their potential roles in defining cerebellar identity and contributing to neuropsychiatric diseases.展开更多
Alzheimer's disease(AD),the most prevalent form of dementia,disproportionately affects the elderly population.While aging is widely recognized as a major risk factor for AD,the precise mechanisms by which aging co...Alzheimer's disease(AD),the most prevalent form of dementia,disproportionately affects the elderly population.While aging is widely recognized as a major risk factor for AD,the precise mechanisms by which aging contributes to the pathogenesis of AD remain poorly understood.In our previous work,the neuropathological changes in the brains of aged cynomolgus monkeys(≥18 years old)following parenchymal cerebral injection of amyloid-β oligomers(AβOs)have been characterized.Here,we extend our investigation to middle-aged cynomolgus monkeys(≤15 years old)to establish an AD model.Surprisingly,immunohistochemical analysis reveals no detectable AD-related pathology in the brains of middle-aged monkeys,even after AβOs injection.In a comprehensive pathological analysis of 38 monkeys,we observe that the amyloid-β(Aβ)burden increases significantly with advancing age.Notably,the density of Aβ plaques is markedly higher in the ventral regions compared with the dorsal regions of aged monkey brains.Furthermore,we demonstrate that tau phosphorylation coincides with the accumulation of extensive Aβplaques and exhibits a positive correlation with Aβ burden in aged monkeys.Collectively,these findings underscore the critical role of the aged brain in providing the necessary conditions for AβO-induced AD pathologies in cynomolgus monkeys.展开更多
Elucidating the closest living relatives of extant primates is essential for fully understanding important biological processes related to the genomic and phenotypic evolution of primates, especially of humans. Howeve...Elucidating the closest living relatives of extant primates is essential for fully understanding important biological processes related to the genomic and phenotypic evolution of primates, especially of humans. However, the phylogenetic placement of these primate relatives remains controversial, with three primary hypotheses currently espoused based on morphological and molecular evidence. In the present study, we used two algorithms to analyze differently partitioned genomic datasets consisting of 45.4 Mb of conserved non-coding elements and 393 kb of concatenated coding sequences to test these hypotheses. We assessed different genomic histories and compared with other molecular studies found solid support for colugos being the closest living relatives of primates. Our phylogeny showed Cercopithecinae to have low levels of nucleotide divergence, especially for Papionini, and gibbons to have a high rate of divergence. The MCMCtree comprehensively updated divergence dates of early evolution of Primatomorpha and Primates.展开更多
Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human prim...Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.展开更多
Nonhuman primates exhibit advanced facial display replication behaviors,such as yawn contagion and facial mimicry,which play critical roles for social coordination and communication.These behaviors are increasingly un...Nonhuman primates exhibit advanced facial display replication behaviors,such as yawn contagion and facial mimicry,which play critical roles for social coordination and communication.These behaviors are increasingly understood through the behavioral ecology view as predictive signals that reduce uncertainty in social interactions.Recent studies highlight interspecific variability:while yawn contagion synchronizes group vigilance and strengthens intergroup cohesion in species like geladas(Theropithecus gelada),its absence in lowland gorillas(Gorilla gorilla)underscores the role of social structure.Rapid facial mimicry,prevalent in play contexts across great apes and New World monkeys,facilitates real-time behavioral alignment,whereas delayed facial mimicry in chimpanzees(Pan troglodytes)reflects complex social negotiation.Neurobiological mechanisms implicate the mirror neuron system alongside distributed networks(e.g.,posterior cingulate,insula),though debates persist on their innateness versus associative origins.Emerging technologies,such as deep learning,reveal nuanced facial expressions in species like golden snubnosed monkeys(Rhinopithecus roxellana),linking morphological variations to multifunctional communication.This synthesis integrates cross-species comparisons,contextual influences,and theoretical advances to elucidate how facial display replication enhances social cohesion and adaptive strategies,hoping to provide novel insights into the origins of primate social cognition and its implications for understanding human emotional and communicative evolution.展开更多
Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the comple...Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.展开更多
BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cell...BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.展开更多
Transplantation therapy for diabetes in humans is limited by the low availability of human donor whole pancreas or islets. Outcomes are complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy...Transplantation therapy for diabetes in humans is limited by the low availability of human donor whole pancreas or islets. Outcomes are complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome supply problems. Implantation of tissue obtained early during embryogenesis is a way to reduce transplant immunogenicity. Pig insulin is biologically active in humans. In that regard the pig is an appropriate xenogeneic organ donor. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation [embryonic day 28 (E28)] engraft long-term in rhesus macaques. Endocrine cells originating from embryonic pig pancreas transplanted in host mesentery migrate to mesenteric lymph nodes, engraft, differentiate and improve glucose tolerance in rhesus macaques without the need for immune suppression. Transplantation of embryonic pig pancreas is a novel approach towards beta cell replacement therapy that could be applicable to humans.展开更多
This paper investigates the impacts of forest cover and spatial structure changes on the forest landscape across Afi-Mbe-Okwangwo protected area of Cross River State, Nigeria and its corresponding implication on two e...This paper investigates the impacts of forest cover and spatial structure changes on the forest landscape across Afi-Mbe-Okwangwo protected area of Cross River State, Nigeria and its corresponding implication on two endangered primates (Cross River Gorilla and Nigeria-Cameroon Chimpanzee) habitat using satellite remote sensing and modeling techniques. Using remote sensing change detection analysis, the spatial extent and annual rate of deforestation for the study area was determined as 34,620 hectares and 1.5% respectively (from 2000 to 2014). The protected areas with highest annual deforestation rates were Afi Mountain Wildlife Sanctuary (2.6%) and Mbe Mountains (2.2%), both prominent for gorilla and chimpanzee sightings and nests. Further investigations on changes to the forest landscape structure revealed high levels of forest fragmentation across the study area for the 14-year period investigated. As a means of further understanding effects of forest landscapes changes across the study area, a 14-year forward simulation was performed using the Markov model as to determine the spatial extent of futuristic forest cover changes. The results showed that if this current trend of forest cover change continued, 28,121 hectares of forests would be lost to deforestation in 2028 (approximately 16% of the total landmass of the entire study area). Using Maxent modeling, suitable primate habitats were predicted and the total coverage determined as 30,940 hectares (54.4% situated in CRNP—Okwangwo division, 29.4% in AMWS, 14.3% in Mbe Mountains and 1.9% in ARFR). Further analysis revealed 6468 hectares of predicted primate habitat were affected by deforestation in 2014 (21% of the predicted primate habitats). These results indicate that suitable primate habitats (particularly for gorillas and chimpanzees) are under immense pressure from deforestation and forest fragmentation. This paper presents a cost effective and time saving approach for determining suitable primate habitats and understanding the effects of forest transition on primate habitat suitability.展开更多
Louis Pierre Gratiolet (1815-1865) was one of the first modern anatomists to pay attention to cerebral convolutions. Born in Sainte-Foy-la-Grande (Gironde), he moved to Paris in 1834 to study medicine, as well as comp...Louis Pierre Gratiolet (1815-1865) was one of the first modern anatomists to pay attention to cerebral convolutions. Born in Sainte-Foy-la-Grande (Gironde), he moved to Paris in 1834 to study medicine, as well as comparative anatomy under Henri de Blainville (1777-1850). In 1842, he accepted de Blainville’s offer to become his assistant at the Muséum d’histoire naturelle and progressively abandoned medicine for comparative anatomy. He undertook a detailed study of brains of human and nonhuman primates and soon realized that the organizational pattern of cerebral convolutions was so predictable that it could serve as a criterion to classify primate groups. He noted that only the deepest sulci exist in lower primate forms, while the complexity of cortical folding increases markedly in great apes and humans. Gratiolet provided the first cogent description of the lobular organization of primate cerebral hemispheres. He saw the insula as a central lobe around which revolved the frontal, parietal, temporal (temporo-sphenoidal) and occipital lobes. He correctly identified most gyri and sulci on all brain surfaces, introduced the term “plis de passage” for some interconnecting gyri, and provided the first description of the optic radiations. In the early 1860s, Gratiolet fought a highly publicized battle against Paul Broca (1824-1880) on the relationship between brain and intelligence. Gratiolet agreed that the brain was most likely the seat of intelligence, but he considered human cognition far too subtle to have any direct relationship with brain size. He argued that a detailed study of the human brain architecture would be more profitable than Broca’s vain speculations on the relationship between brain weight and intelligence, which he considered a monolithic entity. Despite remarkable scientific achievements and a unique teaching capacity, Gratiolet was unable to secure any academic position until three years before his sudden death in Paris at age 49.展开更多
Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biom...Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective to better utilize NHP resources and further foster NHP research in China.展开更多
In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome editing in ...In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates.展开更多
Active exploratory behaviors have often been associated with theta oscillations in rodents,while theta oscillations during active exploration in non-human primates are still not well understood.We recorded neural acti...Active exploratory behaviors have often been associated with theta oscillations in rodents,while theta oscillations during active exploration in non-human primates are still not well understood.We recorded neural activities in the frontal eye field(FEF)and V4 simultaneously when monkeys performed a free-gaze visual search task.Saccades were strongly phase-locked to theta oscillations of V4 and FEF local field potentials,and the phase-locking was dependent on saccade direction.The spiking probability of V4 and FEF units was significantly modulated by the theta phase in addition to the time-locked modulation associated with the evoked response.V4 and FEF units showed significantly stronger responses following saccades initiated at their preferred phases.Granger causality and ridge regression analysis showed modulatory effects of theta oscillations on saccade timing.Together,our study suggests phase-locking of saccades to the theta modulation of neural activity in visual and oculomotor cortical areas,in addition to the theta phase locking caused by saccade-triggered responses.展开更多
Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies hav...Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish diseaseassociated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey(Macaca fascicularis) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral,neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging(MRI), behavioral tasks, flash visual evoked potentials(FVEP),electroretinogram(ERG), optical coherence tomography(OCT), and whole-genome sequencing(WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway.Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion,natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system,especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.展开更多
Since the birth of molecular evolutionary analysis, primates have been a central focus of study and mitochondrial DNA is well suited to these endeavors because of its unique features. Surprisingly, to date no comprehe...Since the birth of molecular evolutionary analysis, primates have been a central focus of study and mitochondrial DNA is well suited to these endeavors because of its unique features. Surprisingly, to date no comprehensive evaluation of the nucleotide substitution patterns has been conducted on the mitochondrial genome of primates. Here, we analyzed the evolutionary patterns and evaluated selection and recombination in the mitochondrial genomes of 44 Primates species downloaded from Genl3ank. The results revealed that a strong rate heterogeneity occurred among sites and genes in all comparisons. Likewise, an obvious decline in primate nucleotide diversity was noted in the subunit rRNAs and tRNAs as compared to the protein-coding genes. Within 13 protein-coding genes, the pattern of nonsynonymous divergence was similar to that of overall nucleotide divergence, while synonymous changes differed only for individual genes, indicating that the rate heterogeneity may result from the rate of change at nonsynonymous sites. Codon usage analysis revealed that there was intermediate codon usage bias in primate protein-coding genes, and supported the idea that GC mutation pressure might determine codon usage and that positive selection is not the driving force for the codon usage bias. Neutrality tests using site-specific positive selection from a Bayesian framework indicated no sites were under positive selection for any gene, consistent with near neutrality. Recombination tests based on the pairwise homoplasy test statistic supported complete linkage even for much older divergent primate species. Thus, with the exception of rate heterogeneity among mitochondrial genes, evaluating the validity assumed complete linkage and selective neutrality in primates prior to phylogenetic or phylogeographic analysis seems unnecessary.展开更多
The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory synd...The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.展开更多
The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acu...The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.展开更多
基金supported by Onassis Foundation(to MT)the National Center for Complementary and Integrative Health(NCCIH),No.R21AT008865(to NM)National Institute of Aging(NIA)/National Institute of Mental Health(NIMH),No.R01AG042512(to NM)
摘要The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.
基金supported by Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology(20200730009)the National Natural Science Foundation of China(81870656)the Natural Science Foundation of Guangdong Province of China(2017A030313610 and 2023A1515012397).
摘要Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve transplantation result in substantial and irreversible visual loss in patients with TON.
摘要Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金supported by the Natural Science Foundation of Guangdong Province(2022A1515010689)National Natural Science Foundation of China(82394422,82371874,82071421,82271902)Department of Science and Technology of Guangdong Province(2021ZT09Y007,2020B121201006)。
摘要Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional activity through the conversion of 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).While DNA methylation is hypothesized to play an essential role in shaping brain identity by influencing gene expression patterns,its direct contribution,especially in primates,remains largely unexplored.This study examined DNA methylation landscapes and transcriptional profiles across four brain regions,including the cortex,cerebellum,striatum,and hippocampus,using samples from 12 rhesus monkeys.The cerebellum exhibited distinct epigenetic and transcriptional signatures,with differentially methylated regions(DMRs)significantly enriched in metabolic pathways.Notably,genes harboring clustered differentially hydroxymethylated regions(DhMRs)overlapped with those implicated in schizophrenia.Moreover,5mC located1 kb upstream of the ATG start codon was correlated with gene expression and exhibited region-specific associations with 5hmC.These findings provide insights into the coordinated regulation of cerebellum-specific 5mC and5hmC,highlighting their potential roles in defining cerebellar identity and contributing to neuropsychiatric diseases.
基金supported in part by the National Key Basic Research and Development Program of China(2019YFA0801402,2018YFA0107200,2018YFA0801402,2018YFA0800100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020501 and XDA16020404)the National Natural Science Foundation of China(32130030,31900454,32470866,32471010,32100800)。
摘要Alzheimer's disease(AD),the most prevalent form of dementia,disproportionately affects the elderly population.While aging is widely recognized as a major risk factor for AD,the precise mechanisms by which aging contributes to the pathogenesis of AD remain poorly understood.In our previous work,the neuropathological changes in the brains of aged cynomolgus monkeys(≥18 years old)following parenchymal cerebral injection of amyloid-β oligomers(AβOs)have been characterized.Here,we extend our investigation to middle-aged cynomolgus monkeys(≤15 years old)to establish an AD model.Surprisingly,immunohistochemical analysis reveals no detectable AD-related pathology in the brains of middle-aged monkeys,even after AβOs injection.In a comprehensive pathological analysis of 38 monkeys,we observe that the amyloid-β(Aβ)burden increases significantly with advancing age.Notably,the density of Aβ plaques is markedly higher in the ventral regions compared with the dorsal regions of aged monkey brains.Furthermore,we demonstrate that tau phosphorylation coincides with the accumulation of extensive Aβplaques and exhibits a positive correlation with Aβ burden in aged monkeys.Collectively,these findings underscore the critical role of the aged brain in providing the necessary conditions for AβO-induced AD pathologies in cynomolgus monkeys.
摘要Elucidating the closest living relatives of extant primates is essential for fully understanding important biological processes related to the genomic and phenotypic evolution of primates, especially of humans. However, the phylogenetic placement of these primate relatives remains controversial, with three primary hypotheses currently espoused based on morphological and molecular evidence. In the present study, we used two algorithms to analyze differently partitioned genomic datasets consisting of 45.4 Mb of conserved non-coding elements and 393 kb of concatenated coding sequences to test these hypotheses. We assessed different genomic histories and compared with other molecular studies found solid support for colugos being the closest living relatives of primates. Our phylogeny showed Cercopithecinae to have low levels of nucleotide divergence, especially for Papionini, and gibbons to have a high rate of divergence. The MCMCtree comprehensively updated divergence dates of early evolution of Primatomorpha and Primates.
基金supported by the National Natural Science Foundation of China(81972064)the Guangdong Basic and Applied Basic Research Foundation(2021A1515111117,2020A1515011415).
摘要Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
基金supported by the National Natural Science Foundation of China(32471565,32371563)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB31020302)+3 种基金the Shaanxi Fundamental Science Research Project for Mathematics and Physics(22JHQ038)Young Elite Scientists Sponsorship Program of Xi’an(959202413086)the Anhui Provincial Natural Science Foundation(2408085QH277)the Natural Science Research Project of Anhui Educational Committee(2024AH050075).
摘要Nonhuman primates exhibit advanced facial display replication behaviors,such as yawn contagion and facial mimicry,which play critical roles for social coordination and communication.These behaviors are increasingly understood through the behavioral ecology view as predictive signals that reduce uncertainty in social interactions.Recent studies highlight interspecific variability:while yawn contagion synchronizes group vigilance and strengthens intergroup cohesion in species like geladas(Theropithecus gelada),its absence in lowland gorillas(Gorilla gorilla)underscores the role of social structure.Rapid facial mimicry,prevalent in play contexts across great apes and New World monkeys,facilitates real-time behavioral alignment,whereas delayed facial mimicry in chimpanzees(Pan troglodytes)reflects complex social negotiation.Neurobiological mechanisms implicate the mirror neuron system alongside distributed networks(e.g.,posterior cingulate,insula),though debates persist on their innateness versus associative origins.Emerging technologies,such as deep learning,reveal nuanced facial expressions in species like golden snubnosed monkeys(Rhinopithecus roxellana),linking morphological variations to multifunctional communication.This synthesis integrates cross-species comparisons,contextual influences,and theoretical advances to elucidate how facial display replication enhances social cohesion and adaptive strategies,hoping to provide novel insights into the origins of primate social cognition and its implications for understanding human emotional and communicative evolution.
摘要Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.
基金Supported by Russian Science Foundation,No.16-15-10432。
摘要BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.
摘要Transplantation therapy for diabetes in humans is limited by the low availability of human donor whole pancreas or islets. Outcomes are complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome supply problems. Implantation of tissue obtained early during embryogenesis is a way to reduce transplant immunogenicity. Pig insulin is biologically active in humans. In that regard the pig is an appropriate xenogeneic organ donor. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation [embryonic day 28 (E28)] engraft long-term in rhesus macaques. Endocrine cells originating from embryonic pig pancreas transplanted in host mesentery migrate to mesenteric lymph nodes, engraft, differentiate and improve glucose tolerance in rhesus macaques without the need for immune suppression. Transplantation of embryonic pig pancreas is a novel approach towards beta cell replacement therapy that could be applicable to humans.
摘要This paper investigates the impacts of forest cover and spatial structure changes on the forest landscape across Afi-Mbe-Okwangwo protected area of Cross River State, Nigeria and its corresponding implication on two endangered primates (Cross River Gorilla and Nigeria-Cameroon Chimpanzee) habitat using satellite remote sensing and modeling techniques. Using remote sensing change detection analysis, the spatial extent and annual rate of deforestation for the study area was determined as 34,620 hectares and 1.5% respectively (from 2000 to 2014). The protected areas with highest annual deforestation rates were Afi Mountain Wildlife Sanctuary (2.6%) and Mbe Mountains (2.2%), both prominent for gorilla and chimpanzee sightings and nests. Further investigations on changes to the forest landscape structure revealed high levels of forest fragmentation across the study area for the 14-year period investigated. As a means of further understanding effects of forest landscapes changes across the study area, a 14-year forward simulation was performed using the Markov model as to determine the spatial extent of futuristic forest cover changes. The results showed that if this current trend of forest cover change continued, 28,121 hectares of forests would be lost to deforestation in 2028 (approximately 16% of the total landmass of the entire study area). Using Maxent modeling, suitable primate habitats were predicted and the total coverage determined as 30,940 hectares (54.4% situated in CRNP—Okwangwo division, 29.4% in AMWS, 14.3% in Mbe Mountains and 1.9% in ARFR). Further analysis revealed 6468 hectares of predicted primate habitat were affected by deforestation in 2014 (21% of the predicted primate habitats). These results indicate that suitable primate habitats (particularly for gorillas and chimpanzees) are under immense pressure from deforestation and forest fragmentation. This paper presents a cost effective and time saving approach for determining suitable primate habitats and understanding the effects of forest transition on primate habitat suitability.
摘要Louis Pierre Gratiolet (1815-1865) was one of the first modern anatomists to pay attention to cerebral convolutions. Born in Sainte-Foy-la-Grande (Gironde), he moved to Paris in 1834 to study medicine, as well as comparative anatomy under Henri de Blainville (1777-1850). In 1842, he accepted de Blainville’s offer to become his assistant at the Muséum d’histoire naturelle and progressively abandoned medicine for comparative anatomy. He undertook a detailed study of brains of human and nonhuman primates and soon realized that the organizational pattern of cerebral convolutions was so predictable that it could serve as a criterion to classify primate groups. He noted that only the deepest sulci exist in lower primate forms, while the complexity of cortical folding increases markedly in great apes and humans. Gratiolet provided the first cogent description of the lobular organization of primate cerebral hemispheres. He saw the insula as a central lobe around which revolved the frontal, parietal, temporal (temporo-sphenoidal) and occipital lobes. He correctly identified most gyri and sulci on all brain surfaces, introduced the term “plis de passage” for some interconnecting gyri, and provided the first description of the optic radiations. In the early 1860s, Gratiolet fought a highly publicized battle against Paul Broca (1824-1880) on the relationship between brain and intelligence. Gratiolet agreed that the brain was most likely the seat of intelligence, but he considered human cognition far too subtle to have any direct relationship with brain size. He argued that a detailed study of the human brain architecture would be more profitable than Broca’s vain speculations on the relationship between brain weight and intelligence, which he considered a monolithic entity. Despite remarkable scientific achievements and a unique teaching capacity, Gratiolet was unable to secure any academic position until three years before his sudden death in Paris at age 49.
基金supported by the National Natural Science Foundation of China(81172876,81273251,U1202228,81471620)the National Special Science Research Program of China(2012CBA01305)+1 种基金the National Science and Technology Major Project(2013ZX10001-002,2012ZX10001-007)the Knowledge Innovation Program of CAS(KSCX2-EW-R-13,KJZD-EW-L10-02)
摘要Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective to better utilize NHP resources and further foster NHP research in China.
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(31130051)
摘要In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates.
基金We are grateful for the financial support from the National Natural Science Foundation of China(31671108 and 31800900)the National Key R&D Program of China(2017YFC1307500)+1 种基金the Shenzhen Science and Technology Innovation Commission(JCYJ20180508152240368)the Shenzhen Basic Research Program(JCYJ20200109114805984).
摘要Active exploratory behaviors have often been associated with theta oscillations in rodents,while theta oscillations during active exploration in non-human primates are still not well understood.We recorded neural activities in the frontal eye field(FEF)and V4 simultaneously when monkeys performed a free-gaze visual search task.Saccades were strongly phase-locked to theta oscillations of V4 and FEF local field potentials,and the phase-locking was dependent on saccade direction.The spiking probability of V4 and FEF units was significantly modulated by the theta phase in addition to the time-locked modulation associated with the evoked response.V4 and FEF units showed significantly stronger responses following saccades initiated at their preferred phases.Granger causality and ridge regression analysis showed modulatory effects of theta oscillations on saccade timing.Together,our study suggests phase-locking of saccades to the theta modulation of neural activity in visual and oculomotor cortical areas,in addition to the theta phase locking caused by saccade-triggered responses.
基金supported by the National Natural Science Foundation of China(81870682,81961128021,81670885)National Key R&D Program of China(2022YEF0203200,2021ZD0200103,2018YFA0108300)+2 种基金Guangdong Provincial Key R&D Programs(2018B030335001,2018B030337001)Local Innovative and Research Teams Project of Guangdong(2017BT01S138)Science and Technology Program of Guangzhou(202007030011,202007030010)。
摘要Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish diseaseassociated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey(Macaca fascicularis) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral,neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging(MRI), behavioral tasks, flash visual evoked potentials(FVEP),electroretinogram(ERG), optical coherence tomography(OCT), and whole-genome sequencing(WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway.Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion,natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system,especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.
基金This project was supported by the National Basic Research Program of China (973 Program:2007CB411600)the Natural Science Foundation of China (3063001630570292)
摘要Since the birth of molecular evolutionary analysis, primates have been a central focus of study and mitochondrial DNA is well suited to these endeavors because of its unique features. Surprisingly, to date no comprehensive evaluation of the nucleotide substitution patterns has been conducted on the mitochondrial genome of primates. Here, we analyzed the evolutionary patterns and evaluated selection and recombination in the mitochondrial genomes of 44 Primates species downloaded from Genl3ank. The results revealed that a strong rate heterogeneity occurred among sites and genes in all comparisons. Likewise, an obvious decline in primate nucleotide diversity was noted in the subunit rRNAs and tRNAs as compared to the protein-coding genes. Within 13 protein-coding genes, the pattern of nonsynonymous divergence was similar to that of overall nucleotide divergence, while synonymous changes differed only for individual genes, indicating that the rate heterogeneity may result from the rate of change at nonsynonymous sites. Codon usage analysis revealed that there was intermediate codon usage bias in primate protein-coding genes, and supported the idea that GC mutation pressure might determine codon usage and that positive selection is not the driving force for the codon usage bias. Neutrality tests using site-specific positive selection from a Bayesian framework indicated no sites were under positive selection for any gene, consistent with near neutrality. Recombination tests based on the pairwise homoplasy test statistic supported complete linkage even for much older divergent primate species. Thus, with the exception of rate heterogeneity among mitochondrial genes, evaluating the validity assumed complete linkage and selective neutrality in primates prior to phylogenetic or phylogeographic analysis seems unnecessary.
基金supported by the National Key R&D Program of China(2020YFC0842000 to Z.M.Yuan and 2020YFC0842100 to C.Shan)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010101 to Z.L.Shi)+1 种基金the China Natural Science Foundation(82041013 to P.Zhou)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CAS)(2019328 to X.L.Yang)。
摘要The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.
摘要The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.