Jump further,leap higher,and consolidate stronger:A brief review of the long-term partnership between Kunming Institute of Zoology(KIZ)and the Chinese University of Hong Kong(CUHK)in bioresources and molecular research

The molecular etiologies of many prevalent diseases stem from genetic variations that arise during evolution and natural selection,as well as from environmental effects.The study of genetic diversity in human populations and analysis of molecular evolution in primates and other animal species can provide important insights regarding the pathogenesis of common diseases in both human and animal populations.

Catalog of insect type specimens preserved at the Kunming Institute of Zoology,Chinese Academy of Science with corrections of some specimens

This article presents a list of insect types preserved in Kunming Natural History Museum of Zoology （KNHMZ）. As of March, 2015, 3412 type specimens belonging to 266 species/subspecies of 37 families in 9 orders （Odonata, Isoptera, Mantodea, Orthoptera, Hemiptera, Coleoptera, Diptera, Hymenoptera and Lepidoptera） are included. Information corrections of some specimens are provided in this article.

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

Bird species composition and conservation challenges in the Gaoligong Mountains, one of the most diverse bird areas in the world

The Gaoligong Mountains(GLGM),located in southwestern China,extend north to south along the western border of the Hengduan Mountains,spanning approximately 600 km.In this study,we consolidated findings from 17 bird surveys conducted in the GLGM between 2010 and 2022.We found that the GLGM harbors tremendous bird diversity,with a total of 796 documented bird species in the region.Nearly a quarter(23.0%)of these species are listed as state key protected species or as Chinese and global threatened species.Analysis of species richness at the county level showed a decreasing trend with increasing latitude,with the greatest diversity in Yingjiang(661 species).Observations indicated that the GLGM belongs to the Oriental realm,primarily composed of bird species from southern and southwestern China.The GLGM plays an important role in avian conservation by sheltering exceptional bird diversity,providing corridors and flyways for bird migration and dispersal,and mitigating the effects of climate change.In response to the conservation needs of birds and other wildlife,the Chinese government has established numerous protected areas within the GLGM.Despite these efforts,avian conservation still faces considerable challenges in the GLGM due to limitations in the protected area network,transboundary nature of the regions,and existing gaps in monitoring and research.

Mammals of Gaoligong Mountain in China:Diversity,distribution,and conservation

Gaoligong Mountain(hereafter,GLGM)is located at the intersection of Myanmar and China’s Yunnan Province and Xizang Zizhiqu,and spans three globally significant biodiversity hotspots:the Himalayas,Indo-Burma,and the Mountains of Southwest China.Although surveys of mammals in this ecologically important region have a long history,there is no comprehensive systematic checklist and distribution account of the mammals of GLGM.Here,we compiled a mammal species checklist of GLGM based on thorough field investigations and literature reviews.We also examined specimen collections and applied camera trapping surveys to explore the region’s mammal diversity and distribution patterns.We recorded 212 mammal species in nine orders,33 families,and 119 genera,which accounts for 30.5%of China’s mammal species,and a high proportion of nationally protected(50)and globally threatened(29)species.Mammal species richness showed a symmetrical unimodal curve along the elevation gradient,peaking at intermediate elevations(2000 to 2500 m above sea level(asl)),and increasing generally from south to north,slightly higher in the east slope than in the west.Cluster analysis and non-metric multidimensional scaling revealed three distinct elevational assemblages(<900 m asl.,900-3500 m asl.,and>3500 m asl)and significant south-to-north variation,but no substantial differences between the east and west slopes.The GLGM present a unique conservation value due to the high proportions of rare and endangered mammal species,complex faunal composition,high endemism,and being the distribution boundary for many species.This study is an important phased account of mammal diversity in GLGM and makes a prospect for future research.

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.

Impact of letters to the editor and publications in 2023

A letter to the editor constitutes a short communication addressing a range of topics pertinent to the readership of a journal(Dkhar,2018).This format offers several benefits,such as timeliness,accessibility,innovation,and conciseness,thereby serving as an effective means to disseminate cuttingedge scientific ideas.Over the past five years,there has been a considerable increase in the number of letters published,representing the highest growth rate(approximately 20%)observed in the last three decades(Figure 1A).In the field of academic publishing,letters to the editor are typically more concise than typical research papers.

Obituary:Prof.Yun Zhang(1963-2023)-A scientist focused on toxins and their underlying mechanisms to decipher human diseases

Prof.Yun Zhang was born on 9 July 1963 in Kunming,Yunnan,China,during a tumultuous period which he often referenced.Throughout his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of human diseases.His educational journey was marked by frequent changes in schools due to his parents’occupational relocations.However,despite these challenges,he consistently displayed diligence and was admitted to the East China University of Science and Technology,Shanghai,after completing high school in 1980.He remained an active and loyal member of the School of Biotechnology at the university.

Early results of the integrative epigenomic-transcriptomic landscape of colorectal adenoma and cancer

BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Characterization of long-term ex vivo expansion of tree shrew spermatogonial stem cells

Tree shrews(Tupaia belangeri chinensis)share a close relationship to primates and have been widely used in biomedical research.We previously established a spermatogonial stem cell(SSC)-based gene editing platform to generate transgenic tree shrews.However,the influences of long-term expansion on tree shrew SSC spermatogenesis potential remain unclear.Here,we examined the in vivo spermatogenesis potential of tree shrew SSCs cultured across different passages.We found that SSCs lost spermatogenesis ability after long-term expansion(>50 passages),as indicated by the failure to colonize the seminiferous epithelium and generate donor spermatogonia(SPG)-derivedspermatocytesor spermatids marking spermatogenesis.RNA sequencing(RNA-seq)analysis of undifferentiated SPGs across different passages revealed significant gene expression changes after sub-culturing primary SPG lines for more than 40 passages on feeder layers.Specifically,DNA damage response and repair genes(e.g.,MRE11,SMC3,BLM,and GEN1)were down-regulated,whereas genes associated with mitochondrial function(e.g.,NDUFA9,NDUFA8,NDUFA13,and NDUFB8)were up-regulated after expansion.The DNA damage accumulation and mitochondrial dysfunction were experimentally validated in high-passage cells.Supplementation with nicotinamide adenine dinucleotide(NAD+)precursor nicotinamide riboside(NR)exhibited beneficial effects by reducing DNA damage accumulation and mitochondrial dysfunction in SPG elicited by long-term culture.Our research presents a comprehensive analysis of the genetic and physiological attributes critical for the sustained expansion of undifferentiated SSCs in tree shrews and proposes an effective strategy for extended in vitro maintenance.

Generic classification of Asian horned toads(Anura:Megophryidae: Megophryinae) and monograph of Chinese species

The subfamily Megophryinae,as a representative batrachian group of the Oriental Realm and one of the most diverse groups of amphibians,has attracted considerable attention due to continued conjecture regarding its generic classification and failure to reach a satisfactory consensus.China boasts the richest diversity of Asian horned toads,containing some two thirds of the total species cataloged.However,most species have a complicated taxonomic history,resulting in multiple misidentifications.As such,an overall clarification of historical records and regional checklists is required.In the current investigation,we established the phylogeny of the Asian horned toads and performed detailed examinations with redefinitions of several important morphological traits.Based on the phylogenetic relationships and morphological differences,we propose a new ten-genus classification for the Asian horned toad subfamily Megophryinae:i.e.,Brachytarsophrys,Atympanophrys,Grillitschia,Sarawakiphrys gen.nov.,Jingophrys gen.nov.,Xenophrys,Megophrys,Pelobatrachus,Ophryophryne,and Boulenophrys.Revisions on the diagnosability,distribution,and content of each genus are provided.Furthermore,we present a careful review of the taxonomic history of Asian horned toad species from China and provide a monograph of congeners,including six species of Brachytarsophrys,four species of Atympanophrys,five species of Jingophrys gen.nov.,10 species of Xenophrys,two species of Ophryophryne,and 60 species of Boulenophrys.Finally,we discuss the importance of traditional morphological traits based on multiple populations in taxonomic work as well as taxonomic inflation caused by the genetic species delimitation.

EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1,TRF2,and RAD50

Telomeres are nucleoprotein structures located at the end of each chromosome,which function in terminal protection and genomic stability.Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo.As relatively long-lived mammals based on body size,bats display unique telomeric patterns,including the upregulation of genes involved in alternative lengthening of telomeres(ALT),DNA repair,and DNA replication.At present,however,the relevant molecular mechanisms remain unclear.In this study,we performed cross-species comparison and identified EPAS1,a well-defined oxygen response gene,as a key telomeric protector in bat fibroblasts.Bat fibroblasts showed high expression of EPAS1,which enhanced the transcription of shelterin components TRF1 and TRF2,as well as DNA repair factor RAD50,conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion.Based on a human single-cell transcriptome atlas,we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation.Using in vitro-cultured human pulmonary endothelial cells,we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans.In addition,the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence.In conclusion,we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging,drawing insights from the longevity of bats.

Harvesting the fruits of the first stage of the Primate Genome Project

Primates are highly successful mammals with significant morphological,behavioral,and physiological diversity.Studying the genomes of non-human primates,as the closest relative of humans,can provide insights into human evolution,genetic structure,and potential drug targets relevant to human health,thus making important contributions to medical research.Additionally,primate genome research can support ecological balance and resource conservation and promote sustainable development and human well-being.Despite the existence of more than 500 primate species belonging to 80 genera and 16 families worldwide,with new species still being discovered in recent years(Fan et al.,2017;Khanal et al.,2021;Roos et al.,2020),genome sequencing efforts have been limited to a relatively small number of species from only 22 genera(Ensembl v103).Notably,approximately 72%of primate genera remain unsequenced,leading to significant knowledge gaps in our understanding of their evolutionary history.This situation presents considerable challenges for the development,utilization,and protection of primate genetic resources.It is for these compelling reasons that we initiated the Primate Genome Project(PGP)(Wu et al.,2022).

Generation of a tree shrew breast cancer model using lentivirus expressing PIK3CA-H1047R

DEAR EDITOR,Breast cancer is the most common malignant tumor in women,posing a serious threat to health. Tree shrews(Tupaia belangeri chinensis) are evolutionarily closer to humans than rodents and are emerging as an attractive experimental animal model for breast cancer. The PIK3CA gene is frequently mutated in both human and tree shrew breast tumors. Herein, we effectively overexpressed PIK3CA-H1047R in the mammary epithelial cells of tree shrews using a lentivirus to induce breast tumors.

Hiding on jagged karst pinnacles:A new microendemic genus and species of a limestone-dwelling agamid lizard(Squamata:Agamidae:Draconinae)from Khammouan Province,Laos

We describe a unique new species and genus of agamid lizard from the karstic massifs of Khammouan Province,central Laos.Laodracon carsticola Gen.et sp.nov.is an elusive medium-sized lizard(maximum snout-vent length101 mm)specifically adapted to life on limestone rocks and pinnacles.To assess the phylogenetic position of the new genus amongst other agamids,we generated DNA sequences from two mitochondrial gene fragments(16S rRNA and ND2)and three nuclear loci(BDNF,RAG1 and c-mos),with a final alignment comprising 7418 base pairs for 64 agamid species.Phylogenetic analyses unambiguously place the new genus in the mainland Asia subfamily Draconinae,where it forms a clade sister to the genus Diploderma from East Asia and the northern part of Southeast Asia.Morphologically,the new genus is distinguished from all other genera in Draconinae by possessing a notably swollen tail base with enlarged scales on its dorsal and ventral surfaces.Our work provides further evidence that limestone regions of Indochina represent unique“arks of biodiversity”and harbor numerous relict lineages.To date,Laodracon carsticola Gen.et sp.nov.is known from only two adult male specimens and its distribution seems to be restricted to a narrow limestone massif on the border of Khammouan and Bolikhamxai provinces of Laos.Additional studies are required to understand its life history,distribution,and conservation status.

Tiger reappearance in Medog highlights the conservation values of the region for this apex predator

In less than a century,Asia’s largest apex predator,the tiger(Panthera tigris),has been relegated to isolated populations surviving in only a small fraction of its historical range.The Medog region,located in Xizang Zizhiqu(Tibet),China,is an important stronghold for this ecologically important apex predator.To enhance our knowledge of the status of tigers in the Medog region,we carried out a systematic camera trapping survey combined with socioecological data collection between April 2020 and May 2022.We surveyed a 1769 km2 area across the Medog region,with a total valid sampling effort of 43163 camera days from 322 camera stations.We also collected socioecological data from 27 forest rangers.We documented tigers at eight camera trapping stations at two villages separated by the Jinzhu Tsangpo River,confirming the presence of at least one adult male individual within the Medog region.These new records were observed over 80 km northeast of the first record in 2019.Additionally,residents reported tiger sightings in 2020 and likely tiger pugmarks in 2021.These spatially and temporally separate records of tigers in the Medog region provide valuable data for informing species-oriented conservation management and highlight the importance of the region for tiger movement and population expansion.However,although encouraging,our survey also detected human activities that may threaten tigers and their potential prey.Ensuring the future survival of tigers in the Medog region entails anti-poaching patrols and long-term camera trapping efforts.In addition,it is also important to identify and establish corridors that connect the Medog region with the adjacent Zangnan region,which also harbors an important population of tigers.

Meeting report:the 4^(th) symposium on animal models of non-human primates in Kunming,Yunnan,China

From 2 to 4 November, 2016, the 4th Symposium on Animal Models of Non-Human Primates （NHP） was held in Kunming, Yunnan, China. This meeting was organized by the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences （CAS） ＆ Yunnan Province Kunming Primate Research Center （KPRC）, Zoological Research, and Kunming Institute of Zoology （KIZ）, CAS.