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| Open AccessSex-specific developmental gene expression atlas unveils dimorphic gene networks in C. elegans
Genetic sex introduces variation in phenotypic traits in sexually reproducing organisms. Here, the authors report a developmental gene expression atlas for C. elegans males and hermaphrodites, highlighting the key role of the insulin-like peptide INS-39 in male development and suggesting genetic underpinnings of sexual dimorphism.
- Rizwanul Haque
- , Sonu Peedikayil Kurien
- & Meital Oren-Suissa
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Article
| Open AccessSex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus
Schizophrenia research has traditionally overlooked sex differences. Here, the authors show the importance of sex-based analysis across multi-brain regions by identifying sex-specific genes and genetic interactions in schizophrenia and sex-specific risk.
- Kynon J. M. Benjamin
- , Ria Arora
- & Jennifer A. Erwin
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| Open AccessFunctional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy
Human cortical maturation is organized along the sensorimotor-association axis. Here, the authors investigate in multiple cohorts if the development of functional connectivity during adolescence conforms to this hierarchy.
- Audrey C. Luo
- , Valerie J. Sydnor
- & Theodore D. Satterthwaite
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Article
| Open AccessFunctional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development
Cell metabolism has emerged as a major factor implicated in human brain evolution. Here, the authors show that an ape-specific enzyme enhances the ability of a human-specific enzyme to increase glutaminolysis and therefore expand the size of the human neocortex.
- Lei Xing
- , Vasiliki Gkini
- & Takashi Namba
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Article
| Open AccessComplex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons
Connecting cerebral organoids with an axon bundle models inter-regional projections and enhances neural activity. Optogenetic stimulation induces short-term plasticity, offering insights into macroscopic circuit development and functionality.
- Tatsuya Osaki
- , Tomoya Duenki
- & Yoshiho Ikeuchi
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Article
| Open AccessGlobal spatiotemporal synchronizing structures of spontaneous neural activities in different cell types
Neural mechanisms underlying brain-wide synchronization are not fully understood. Here authors show that traveling waves are prevalent in both excitatory and inhibitory neural populations, more pronounced in glutamatergic neurons, vary across developmental stages, and are associated with functional connections and gene expression.
- Liang Shi
- , Xiaoxi Fu
- & Pengcheng Li
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Article
| Open AccessTransient expression of the neuropeptide galanin modulates peripheral‑to‑central connectivity in the somatosensory thalamus during whisker development in mice
The function of transient neuropeptides in developmental roles in the nervous system remains elusive. Here, authors demonstrate that galanin shapes synaptic wiring in the whisker pathway, a fundamental sensory modality for infant rodents before eye opening.
- Zsofia Hevesi
- , Joanne Bakker
- & Tibor Harkany
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| Open AccessRemodeling of the postsynaptic proteome in male mice and marmosets during synapse development
The proteomic changes that occur during synapse development are not fully understood. In this work, the authors characterise the postsynaptic proteome changes that occur during development in male mice and marmosets.
- Takeshi Kaizuka
- , Takehiro Suzuki
- & Toru Takumi
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Article
| Open AccessStructure and function of Semaphorin-5A glycosaminoglycan interactions
Semaphorin 5A (Sema5A) forms complexes with heparan and chondroitin sulfate proteoglycans to regulate neuronal migration. Here, the authors show that the thrombospondin-like repeat 4 (TSR4) of Sema5A enables glycosaminoglycan association, multimerization, and neural progenitor cell distribution.
- Gergely N. Nagy
- , Xiao-Feng Zhao
- & E. Yvonne Jones
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Article
| Open AccessCondensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster
Mutations in condensin subunits cause microcephaly, but the underlying molecular mechanisms remain elusive. Here, the authors show that unrestricted retrotransposable element activity impairs brain development in condensin insufficient organisms.
- Bert I. Crawford
- , Mary Jo Talley
- & Michelle S. Longworth
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| Open AccessThe AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions
Mitochondria emerged as essential actors of neural circuits development. Here, the authors uncovered that the AMPK-related kinase NUAK1 controls axonal mitochondrial metabolism through the regulation of the mitochondrial microprotein BRAWNIN.
- Marine Lanfranchi
- , Sozerko Yandiev
- & Julien Courchet
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Article
| Open AccessSingle cell atlas of Xenoturbella bocki highlights limited cell-type complexity
Recent phylogenetic analyses have identified orphan clades, including Xenacoelomorphs, that can offer insights into bilaterian evolution. Here they generate a cell type atlas of Xenoturbella bockithat highlights cellular diversity in the nervous system and other tissues, reinforcing the idea of parallel evolution of cell types across animals.
- Helen E. Robertson
- , Arnau Sebé-Pedrós
- & Heather Marlow
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Article
| Open AccessPopulation-wide cerebellar growth models of children and adolescents
The development of the human cerebellum is not well understood. Here, the authors analyse a large sample of neuroimaging scans from children and adolescents to develop growth models of the cerebellum which mirror age-related developmental trajectories of behaviour and function.
- Carolin Gaiser
- , Rick van der Vliet
- & Ryan L. Muetzel
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Article
| Open AccessTBC1D23 mediates Golgi-specific LKB1 signaling
The LKB1 signaling is differentially regulated and has distinct functions at different subcellular compartments. Tu et al reports that TBC1D23 specifically regulates Golgi-LKB1 signaling and link this pathway to neurodevelopment disorders.
- Yingfeng Tu
- , Qin Yang
- & Da Jia
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Article
| Open AccessImportin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
Myelinated axons vary in diameter by over 100-fold. Here, the authors identify a role for the nuclear transport receptor importin 13 in axon diameter growth and corresponding increases to conduction speed along myelinated axons.
- Jenea M. Bin
- , Daumante Suminaite
- & David A. Lyons
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Article
| Open AccessSea lamprey enlightens the origin of the coupling of retinoic acid signaling to vertebrate hindbrain segmentation
Retinoic acid signaling is involved in patterning the embryonic antero-posterior axis, and also regulates hindbrain segmentation in jawed vertebrates. Here they show that retinoic acid signaling plays important roles in hindbrain segmentation in a jawless vertebrate, the lamprey, thus indicating this feature of hindbrain development is conserved in all vertebrates.
- Alice M. H. Bedois
- , Hugo J. Parker
- & Robb Krumlauf
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Article
| Open AccessIntrauterine growth and the tangential expansion of the human cerebral cortex in times of food scarcity and abundance
The human cerebral cortex grows the fastest before birth. Here, the authors find positive associations between cortical expansion and both maternal and fetal birthweight genetics, and that the effects vary across years of birth.
- Daniel E. Vosberg
- , Igor Jurisica
- & Tomáš Paus
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| Open AccessNeonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment
Neonatal brain dynamics are not well understood. Here, the authors characterise brain transient states in neonates, and show that preterm infants display altered whole brain dynamics and an atypical repertoire of regional transient states, which are associated with behavioural outcomes at 18 months of age.
- Lucas G. S. França
- , Judit Ciarrusta
- & Dafnis Batalle
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Article
| Open AccessNeuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation
The glutamate transporter GLAST in astrocyte regulates synapse function by glutamate clearance. Here, the authors show that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synaptogenesis through the intercellular association with GLAST in the developing cerebellum.
- Ken-ichi Dewa
- , Nariko Arimura
- & Mikio Hoshino
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| Open AccessiPSC-derived models of PACS1 syndrome reveal transcriptional and functional deficits in neuron activity
PACS1 syndrome is a neurodevelopmental disorder resulting from a de novo p.R203W variant in phosphofurin acidic cluster sorting protein 1 (PACS1). Here the authors use cortical organoids to investigate the impact of this variant on neurodevelopment.
- Lauren Rylaarsdam
- , Jennifer Rakotomamonjy
- & Alicia Guemez-Gamboa
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| Open AccessA developmental increase of inhibition promotes the emergence of hippocampal ripples
The developmental trajectory of hippocampal ripples, the electrical signature of long term memory storage, is poorly understood. Here, the authors show that their delayed appearance is mechanistically linked to the maturation of inhibition.
- Irina Pochinok
- , Tristan M. Stöber
- & Ileana L. Hanganu-Opatz
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| Open AccessFunctional neuronal circuits emerge in the absence of developmental activity
How functional neuronal circuits are established during development is not fully understood. Here the authors show, by raising fish in the dark and under anesthesia, that brain activity is not needed for the development of complex, decision-making circuits.
- Dániel L. Barabási
- , Gregor F. P. Schuhknecht
- & Florian Engert
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| Open AccessNon-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis
Although functional interactions between receptors shape brain cell communication, their direct interaction remains elusive. Here, authors monitor the weak and transient interaction between NMDA and dopamine receptors, which tune synaptogenesis.
- Nathan Bénac
- , G. Ezequiel Saraceno
- & Laurent Groc
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Article
| Open AccessEssential transcription factors for induced neuron differentiation
Using integrative multi-omics and CRISPR knock-out of all ~1,900 transcription factors, the authors identify essential transcription factors required for Neurogenin-driven differentiation of human cortical neurons.
- Congyi Lu
- , Görkem Garipler
- & Neville E. Sanjana
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Article
| Open AccessD-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia
Modulation of NMDA receptors via D-serine has been investigated as therapeutic strategy in schizophrenia. Here the authors show that D-serine rescues synaptic and intrinsic inhibitory control of cingulate pyramidal neurons, via modulation of parvalbumin neuron excitability, in a mouse model of neurodevelopmental cognitive dysfunction.
- Xiao-Qin Zhang
- , Le Xu
- & Hao-Wei Shen
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Article
| Open AccessPuckered and JNK signaling in pioneer neurons coordinates the motor activity of the Drosophila embryo
How the stereotypical architecture of the nervous system is generated, and how this underlies function, is not well understood. Here, the authors show that JNK signaling in Drosophila pioneer neurons directs its structural organization, required for motor coordination.
- Katerina Karkali
- , Samuel W. Vernon
- & Enrique Martín-Blanco
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Article
| Open AccessCXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
Regulation of cell polarity is key to ensure directed cell migration. Here, Atkins et al. identify the primary cilium cAMP/cGMP ratio as a master regulator of the cell polarity of migrating cortical interneurons downstream of the CXCL12 chemokine.
- Melody Atkins
- , Maud Wurmser
- & Christine Métin
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Article
| Open AccessIsochronic development of cortical synapses in primates and mice
How synapse development correlates with lifespan is unknown. Here, the authors show isochronic synapse development in mouse and primate despite disparate lifespans. As a result, synapse accumulation and reduction finishes in neonatal primates but spans nearly the entire life of the mouse.
- Gregg Wildenberg
- , Hanyu Li
- & Narayanan Kasthuri
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Article
| Open AccessThe genetic relationships between brain structure and schizophrenia
Schizophrenia is considered a brain disorder. Here, authors show genetic overlap between brain structure and schizophrenia that was strongest in the hubs of structural covariance networks and concentrated three chromosomal regions.
- Eva-Maria Stauffer
- , Richard A. I. Bethlehem
- & Edward T. Bullmore
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Article
| Open AccessTemporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity
PSC-brain organoids are typically formed by static medium switches. Here, authors show that a temporal morphogen gradient during neural induction allows the formation of well-specified cortical organoids with a self-organized single neuroepithelium.
- Anna Pagliaro
- , Roxy Finger
- & Benedetta Artegiani
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Article
| Open AccessAutophagy drives the conversion of developmental neural stem cells to the adult quiescent state
Neural stem cells in the adult mammalian brain derive from proliferating precursors that are spared as dormant reservoirs during development. Here, the authors show that autophagy is required for neural stem cells to transition to the adult quiescent state.
- Isabel Calatayud-Baselga
- , Lucía Casares-Crespo
- & Helena Mira
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Article
| Open AccessSingle-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development
Human cerebellar development is fundamentally linked to its function. Here, the authors combine single-cell transcriptomics, spatial transcriptomics, and single-cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development.
- Suijuan Zhong
- , Mengdi Wang
- & Qian Wu
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| Open AccessThe homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling
Synapse elimination is a critical process in the maturation of brain circuitry. Here the authors identify a key transcriptional program in Caenorhabditis elegans that directs the elimination of juvenile synapses during developmental circuit rewiring.
- Kellianne D. Alexander
- , Shankar Ramachandran
- & Michael M. Francis
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Article
| Open AccessVirtual lesions in MEG reveal increasing vulnerability of the language network from early childhood through adolescence
The robustness of the brain’s language network to injury throughout development is not well understood. Here, the authors use an MEG dataset of children listening to stories to show that the brain connectivity of younger children is more robust to simulated lesions.
- Brady J. Williamson
- , Hansel M. Greiner
- & Darren S. Kadis
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Article
| Open AccessMicroglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication
Exposure to cannabis in adolescence is associated with increased risk of psychiatric disorders. Here, in a mouse model of 16p11.2 duplication, the authors identified a role of microglial Cnr1 for mediating the adverse effect of THC exposure on mPFC maturation and social memory.
- Yuto Hasegawa
- , Juhyun Kim
- & Atsushi Kamiya
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Article
| Open AccessKDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors
Zhang et al. report that KDM2B-∆CxxC activated Wnt signaling in the developing hippocampi, where the migration and differentiation of neural progenitors were blocked. KDM2B-∆CxxC mice exhibited defects of hippocampal morphology and related behaviors.
- Bo Zhang
- , Chen Zhao
- & Yan Zhou
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| Open AccessThalamocortical control of cell-type specificity drives circuits for processing whisker-related information in mouse barrel cortex
Excitatory spiny stellate neurons in the somatosensory cortex are shaped by innervating thalamic inputs and unique expression of genes. Here, the authors show that these neurons play a crucial role in processing distinct whisker signals and forming specialized circuits for sensory perception.
- Timothy R. Young
- , Mariko Yamamoto
- & Tomomi Shimogori
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Article
| Open AccessCelf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex
While progress in early human cortical development is acknowledged, a limited understanding persists regarding transcriptomic and translational profiles in subplate neurons. Here, the authors discovered an enrichment of autism spectrum disorder risk genes in subplate neurons, underscoring the crucial role played by the RNA-binding protein CELF4 in translating synaptic mRNAs during neocortical development.
- Iva Salamon
- , Yongkyu Park
- & Mladen-Roko Rasin
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Article
| Open AccessRetina-derived signals control pace of neurogenesis in visual brain areas but not circuit assembly
How does sensory input shape cellular composition and circuit structure of the brain during development? This study shows that, without connections to the retina, neurons in visual brain areas differentiate and wire up normally, albeit more slowly.
- Shachar Sherman
- , Irene Arnold-Ammer
- & Herwig Baier
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Article
| Open AccessNon-uniform temporal scaling of developmental processes in the mammalian cortex
Marsupial mammals take much longer to develop than similarly sized placental mammals, though how brain development occurs across these different periods is unclear. Here they show that the neurodevelopmental events of cortical neurogenesis, cell migration and axon extension do not all temporally scale to the same extent.
- Annalisa Paolino
- , Elizabeth H. Haines
- & Laura R. Fenlon
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Article
| Open AccessA branching model of lineage differentiation underpinning the neurogenic potential of enteric glia
The enteric nervous system encompasses the gut-intrinsic neuroglial networks that regulate gastrointestinal functions. Based on single-cell analysis, the authors propose a model in which neurogenic differentiation paths branch from a gliogenic trajectory.
- Anna Laddach
- , Song Hui Chng
- & Vassilis Pachnis
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Article
| Open AccessNetwork controllability of structural connectomes in the neonatal brain
Network controllability represents the ease with which the brain switches between mental states and can be inferred from white matter connectivity. Here, the authors show network controllability emerges in infants as early as the third trimester, and that preterm birth disrupts the energy required to drive state transitions.
- Huili Sun
- , Rongtao Jiang
- & Dustin Scheinost
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Article
| Open AccessLoss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice
The role of lactate in the control of microglial function remains poorly investigated. Here, the authors show that lactate promotes lysosomal acidification in microglia, and that mice lacking the lactate transporter MCT4 in these cells display defective brain development and anxiety-like behavior.
- Katia Monsorno
- , Kyllian Ginggen
- & Rosa Chiara Paolicelli
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Article
| Open AccessSulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but their risks for early neurodevelopment remain controversial. Here, the authors showed in zebrafish larvae that sulindac induces GABAergic neuron apoptosis through autophagy activation that leads to hyperactive behavior.
- Wenwei Sun
- , Meimei Wang
- & Zhibin Huang
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Article
| Open AccessAstroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation
How developing astroglia regulate postnatal axon growth is unknown. Here, the authors define an astroglial exosome surface HepaCAM contact mechanism in regulating axon growth and how its antagonization by ApoE coordinates early postnatal pyramidal neuronal development.
- Shijie Jin
- , Xuan Chen
- & Yongjie Yang
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Article
| Open AccessErythropoietin re-wires cognition-associated transcriptional networks
The mechanism and physiological role of brain-expressed Erythropoietin (EPO) is unclear. Here, authors show that the trajectory of pyramidal neurons is maneuvered by EPO, befitting the neurogenic hypothesis of alleviating mood, memory, and cognition.
- Manvendra Singh
- , Ying Zhao
- & Hannelore Ehrenreich
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Article
| Open AccessCombinatorial expression of neurexins and LAR-type phosphotyrosine phosphatase receptors instructs assembly of a cerebellar circuit
Whether presynaptic ‘hub’ adhesion molecules are essential for synapse formation is still unclear. Here, the authors generate sextuple conditional knockout mice that target Neurexins and LAR-PTPRs and find that their combinatorial expression instructs the assembly of a cerebellar circuit.
- Alessandra Sclip
- & Thomas C. Südhof
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| Open AccessAstroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation
Despite a wealth of knowledge on astrocytes, their contribution to cerebrovascular maturation is less known. Here, the authors identify a molecule produced by astrocytes which controls astrocyte morphology and their placement on brain blood vessels.
- Moises Freitas-Andrade
- , Cesar H. Comin
- & Baptiste Lacoste
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Article
| Open AccessSelf-supervised learning with application for infant cerebellum segmentation and analysis
Neuroimaging of the cerebellum in infants has been challenging. Here the authors describe a framework for cerebellum MRI segmentation in infants up to 2 years.
- Yue Sun
- , Limei Wang
- & Li Wang