Optical-neural Stimulation in Non-human Primates:Modulating Brain Function and Behavior

Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.

Advances in spinal cord injury:insights from non-human primates

Spinal cord injury results in significant sensorimotor deficits,currently,there is no curative treatment for the symptoms induced by spinal cord injury.Basic and pre-clinical research on spinal cord injury relies on the development and characterization of appropriate animal models.These models should replicate the symptoms observed in human,allowing for the exploration of functional deficits and investigation into various aspects of physiopathology of spinal cord injury.Non-human primates,due to their close phylogenetic association with humans,share more neuroanatomical,genetic,and physiological similarities with humans than rodents.Therefore,the responses to spinal cord injury in nonhuman primates most likely resemble the responses to traumatism in humans.In this review,we will discuss nonhuman primate models of spinal cord injury,focusing on in vivo assessments,including behavioral tests,magnetic resonance imaging,and electrical activity recordings,as well as ex vivo histological analyses.Additionally,we will present therapeutic strategies developed in non-human primates and discuss the unique specificities of non-human primate models of spinal cord injury.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation

PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease.However,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration.Additionally,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit neurodegeneration.In our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent brains.To extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig tissues.In contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig tissues.Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain.Consistently,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD.These findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.

Defects and asymmetries in the visual pathway of non-human primates with natural strabismus and amblyopia

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.

Achievements and challenges of primate conservation in China

The dual impact of climate change and human activities has precipitated a sharp decline in primate biodiversity globally.China is home to the most diverse primate species in the Northern hemisphere,which face severe ecological threats due to the expansion of modern agriculture,extensive exploitation and consumption of natural resources,and excessive land development during its transition from an agricultural to a modern society.In response,China has implemented various ecological conservation measures,including habitat restoration and protection.These efforts have made substantial strides in biodiversity conservation,with certain regions witnessing an increase in primate populations.In the current study,we conducted a systematic review of historical documents and field research data related to Chinese primates,evaluating the endangered status of primate species in China.Despite improvements in the habitats of most primate species and some population growth,many species still face severe threats,including declining and small populations.Species such as the Myanmar snub-nosed monkey(Rhinopithecus strykeri),eastern black crested gibbon(Nomascus nasutus),and Hainan gibbon(N.hainanus)remain particularly vulnerable due to their limited distribution ranges and extremely small populations.Insufficient scientific data,fragmented information,and not enough studies in conservation biology further compound the challenges.Moreover,there is a notable lack of detailed population monitoring data for species such as the Bengal slow loris(Nycticebus bengalensis),pygmy slow loris(N.pygmaeus),Indochinese gray langur(Trachypithecus crepusculus),Shortridge’s langur(T.shortridgei),and capped langur(T.pileatus),which hinders the development of practical and targeted conservation management strategies.Therefore,for national biodiversity conservation,there is an urgent need for specialized primate surveys,enhancing habitat protection and restoration,and increasing focus on cross-border conservation strategies and regional cooperation.There is also a need to establish a comprehensive and systematic research database platform,conduct continuous and in-depth research in primate biology,and actively engage in the scientific assessment of ecotourism.Additionally,strengthening public awareness and education on wildlife conservation remains essential.Such integrated and systematic efforts will provide scientific support for the current and future conservation and management of primate species in China.

The Grammatical Categorization of Mandarin在/zài:Spatiality,Temporality and Semantic Construal

Mandarin在(pinyin:zài)is the most frequently used character in representing spatial and temporal relationship.Current studies mostly focus on its lexical meaning and syntactic structure while cognitive features of its grammatical categories have been neglected.This paper investigates into the categorization of zài by conducting a morphosyntactic test among College English majors in China.The results show that:prototypes are organizing the grammatical categories of zài at all levels in terms of intra-categorial gradience;the semantic construal of zài construction could significantly influence the accuracy of the grammatical categorization of zài;the syntactic structure can provide viable cue for the identification of grammatical categories of zài;spatiality,temporality and the status of existing are three essential semantic features encoded by zài,the concurrence of which leads to various degree of inter-categorial vagueness,indicating a conflict between the rigid grammatical classification and the indeterminate nature of the grammatical functions of zai,suggesting the necessity to reconsider the efficacy of applying indiscriminately the Anglo-Saxon grammar into the study of Chinese spatial-temporal constructions.

A Study on Second Language Vocabulary Acquisition Under the Categorization Theory

In cognitive linguistics,debates on the status and functions of categorization have been a heated issue.In semantics and second language acquisition,scholars have discussed and achieved vocabulary acquisition from different perspectives and academic levels.Vocabulary learning exerts a fundamental role in second language vocabulary acquisition(SLVA),and it is closely related to learners’cognitive competence.However,studies on second language vocabulary acquisition under the categorization theory in cognitive linguistics have received less attention from linguists when compared with other studies.This paper employs two representative dimensions,the basic-level effect and the prototype effect,under the categorization theory to further delve into the implications on second language vocabulary acquisition.This article first provides a comprehensive introduction to the nature and the approaches of the categorization theory,and then analyzes the relations and implications for second language vocabulary acquisition under the categorization theory from the perspective of the basic-level and the prototype effects.The research results showed that the basic-level effect on SLVA is mainly on the classification of word categories distinguished from the superordinate and subordinate categories,while the prototype effect is more on understanding the complexity and use of word meaning.

Smart Approaches to Efficient Text Mining for Categorizing Sexual Reproductive Health Short Messages into Key Themes

To promote behavioral change among adolescents in Zambia, the National HIV/AIDS/STI/TB Council, in collaboration with UNICEF, developed the Zambia U-Report platform. This platform provides young people with improved access to information on various Sexual Reproductive Health topics through Short Messaging Service (SMS) messages. Over the years, the platform has accumulated millions of incoming and outgoing messages, which need to be categorized into key thematic areas for better tracking of sexual reproductive health knowledge gaps among young people. The current manual categorization process of these text messages is inefficient and time-consuming and this study aims to automate the process for improved analysis using text-mining techniques. Firstly, the study investigates the current text message categorization process and identifies a list of categories adopted by counselors over time which are then used to build and train a categorization model. Secondly, the study presents a proof of concept tool that automates the categorization of U-report messages into key thematic areas using the developed categorization model. Finally, it compares the performance and effectiveness of the developed proof of concept tool against the manual system. The study used a dataset comprising 206,625 text messages. The current process would take roughly 2.82 years to categorise this dataset whereas the trained SVM model would require only 6.4 minutes while achieving an accuracy of 70.4% demonstrating that the automated method is significantly faster, more scalable, and consistent when compared to the current manual categorization. These advantages make the SVM model a more efficient and effective tool for categorizing large unstructured text datasets. These results and the proof-of-concept tool developed demonstrate the potential for enhancing the efficiency and accuracy of message categorization on the Zambia U-report platform and other similar text messages-based platforms.

Text categorization based on fuzzy classification rules tree

To deal with the problem that arises when the conventional fuzzy class-association method applies repetitive scans of the classifier to classify new texts,which has low efficiency, a new approach based on the FCR-tree（fuzzy classification rules tree）for text categorization is proposed.The compactness of the FCR-tree saves significant space in storing a large set of rules when there are many repeated words in the rules.In comparison with classification rules,the fuzzy classification rules contain not only words,but also the fuzzy sets corresponding to the frequencies of words appearing in texts.Therefore,the construction of an FCR-tree and its structure are different from a CR-tree.To debase the difficulty of FCR-tree construction and rules retrieval,more k-FCR-trees are built.When classifying a new text,it is not necessary to search the paths of the sub-trees led by those words not appearing in this text,thus reducing the number of traveling rules.Experimental results show that the proposed approach obviously outperforms the conventional method in efficiency.

Experimental primates and non-human primate(NHP) models of human diseases in China: current status and progress

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.

Application of the genome editing tool CRISPR/Cas9 in non-human primates

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.

A New Approach of Feature Selection for Text Categorization

This paper proposes a new approach of feature selection based on the independent measure between features for text categorization. A fundamental hypothesis that occurrence of the terms in documents is independent of each other, widely used in the probabilistic models for text categorization （TC）, is discussed. However, the basic hypothesis is incom plete for independence of feature set. From the view of feature selection, a new independent measure between features is designed, by which a feature selection algorithm is given to ob rain a feature subset. The selected subset is high in relevance with category and strong in independence between features, satisfies the basic hypothesis at maximum degree. Compared with other traditional feature selection method in TC （which is only taken into the relevance account）, the performance of feature subset selected by our method is prior to others with experiments on the benchmark dataset of 20 Newsgroups.

Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans

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.

A road for a promising future for China＇s primates： The potential for restoration

China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species. However, primarily as a result of forest loss, most of which occurred in historical times, approximately 70% of China＇s primate species have less than 3 000 individuals. Here I evaluate one road for future conservation/development that could produce very positive gains for China＇s primates; namely forest restoration. I argue that for a large scale restoration project to be possible two conditions must be met; the right societal conditions must exist and the right knowledge must be in hand. This evaluation suggests that the restoration of native forest to support many of China＇s primates holds great potential to advance conservation goals and to promote primate population recovery.

Comparison of Text Categorization Algorithms

This paper summarizes several automatic text categorization algorithms in common use recently, analyzes and compares their advantages and disadvantages. It provides clues for making use of appropriate automatic classifying algorithms in different fields. Finally some evaluations and summaries of these algorithms are discussed, and directions to further research have been pointed out. Key words text categorization - naive bayes - KNN - SVM - neural network CLC number TP 391 Foundation item: Supported by the National Natural Science Foundation of China (70031010) and the Research Foundation of Beijing Institute of TechnologyBiography: SHI Yong-feng (1980-), male, Master candidate, research direction: web information mining.

Lazy learner text categorization algorithm based on embedded feature selection

To avoid the curse of dimensionality, text categorization （TC） algorithms based on machine learning （ML） have to use an feature selection （FS） method to reduce the dimensionality of feature space. Although having been widely used, FS process will generally cause information losing and then have much side-effect on the whole performance of TC algorithms. On the basis of the sparsity characteristic of text vectors, a new TC algorithm based on lazy feature selection （LFS） is presented. As a new type of embedded feature selection approach, the LFS method can greatly reduce the dimension of features without any information losing, which can improve both efficiency and performance of algorithms greatly. The experiments show the new algorithm can simultaneously achieve much higher both performance and efficiency than some of other classical TC algorithms.

A Text Categorization System with Soft Real-Time Guarantee

In order to provide predictable runtime performante for text categorization （TC） systems, an innovative system design method is proposed for soft real time TC systems. An analyzable mathematical model is established to approximately describe the nonlinear and time-varying TC systems. According to this mathematical model, the feedback control theory is adopted to prove the system＇s stableness and zero steady state error. The experiments result shows that the error of deadline satisfied ratio in the system is kept within 4 of the desired value. And the number of classifiers can be dynamically adjusted by the system itself to save the computa tion resources. The proposed methodology enables the theo retical analysis and evaluation to the TC systems, leading to a high-quality and low cost implementation approach.

Identification and Categorization of Climate Change Risks

The scientific evidence that climate is changing due to greenhouse gas emission is now incontestable, which may put many social, biological, and geophysical systems in the world at risk. In this paper, we first identified main risks induced from or aggravated by climate change. Then we categorized them applying a new risk categorization system brought forward by Renn in a framework of International Risk Governance Council. We proposed that ＂uncertainty＂ could be treated as the classification criteria. Based on this, we established a quantitative method with fuzzy set theory, in which ＂confidence＂ and ＂likelihood＂, the main quantitative terms for expressing uncertainties in IPCC, were used as the feature parameters to construct the fuzzy membership functions of four risk types. According to the maximum principle, most climate change risks identified were classified into the appropriate risk types. In the mean time, given that not all the quantitative terms are available, a qualitative approach was also adopted as a complementary classification method. Finally, we get the preliminary results of climate change risk categorization, which might iay the foundation for the future integrated risk management of climate change.