The genomic origins of the Bronze Age Tarim Basin mummies.

The identity of the earliest inhabitants of Xinjiang, in the heart of Inner Asia, and the languages that they spoke have long been debated and remain contentious1. Here we present genomic data from 5 individuals dating to around 3000-2800 BC from the Dzungarian Basin and 13 individuals dating to around 2100-1700 BC from the Tarim Basin, representing the earliest yet discovered human remains from North and South Xinjiang, respectively. We find that the Early Bronze Age Dzungarian individuals exhibit a predominantly Afanasievo ancestry with an additional local contribution, and the Early-Middle Bronze Age Tarim individuals contain only a local ancestry. The Tarim individuals from the site of Xiaohe further exhibit strong evidence of milk proteins in their dental calculus, indicating a reliance on dairy pastoralism at the site since its founding. Our results do not support previous hypotheses for the origin of the Tarim mummies, who were argued to be Proto-Tocharian-speaking pastoralists descended from the Afanasievo1,2 or to have originated among the Bactria-Margiana Archaeological Complex3 or Inner Asian Mountain Corridor cultures4. Instead, although Tocharian may have been plausibly introduced to the Dzungarian Basin by Afanasievo migrants during the Early Bronze Age, we find that the earliest Tarim Basin cultures appear to have arisen from a genetically isolated local population that adopted neighbouring pastoralist and agriculturalist practices, which allowed them to settle and thrive along the shifting riverine oases of the Taklamakan Desert.

Triangulation supports agricultural spread of the Transeurasian languages.

The origin and early dispersal of speakers of Transeurasian languages-that is, Japanese, Korean, Tungusic, Mongolic and Turkic-is among the most disputed issues of Eurasian population history1-3. A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements4,5. Here we address this question by 'triangulating' genetics, archaeology and linguistics in a unified perspective. We report wide-ranging datasets from these disciplines, including a comprehensive Transeurasian agropastoral and basic vocabulary; an archaeological database of 255 Neolithic-Bronze Age sites from Northeast Asia; and a collection of ancient genomes from Korea, the Ryukyu islands and early cereal farmers in Japan, complementing previously published genomes from East Asia. Challenging the traditional 'pastoralist hypothesis'6-8, we show that the common ancestry and primary dispersals of Transeurasian languages can be traced back to the first farmers moving across Northeast Asia from the Early Neolithic onwards, but that this shared heritage has been masked by extensive cultural interaction since the Bronze Age. As well as marking considerable progress in the three individual disciplines, by combining their converging evidence we show that the early spread of Transeurasian speakers was driven by agriculture.

Improving multi-population genomic prediction accuracy using multi-trait GBLUP models which incorporate global or local genetic correlation information.

In the application of genomic prediction, a situation often faced is that there are multiple populations in which genomic prediction (GP) need to be conducted. A common way to handle the multi-population GP is simply to combine the multiple populations into a single population. However, since these populations may be subject to different environments, there may exist genotype-environment interactions which may affect the accuracy of genomic prediction. In this study, we demonstrated that multi-trait genomic best linear unbiased prediction (MTGBLUP) can be used for multi-population genomic prediction, whereby the performances of a trait in different populations are regarded as different traits, and thus multi-population prediction is regarded as multi-trait prediction by employing the between-population genetic correlation. Using real datasets, we proved that MTGBLUP outperformed the conventional multi-population model that simply combines different populations together. We further proposed that MTGBLUP can be improved by partitioning the global between-population genetic correlation into local genetic correlations (LGC). We suggested two LGC models, LGC-model-1 and LGC-model-2, which partition the genome into regions with and without significant LGC (LGC-model-1) or regions with and without strong LGC (LGC-model-2). In analysis of real datasets, we demonstrated that the LGC models could increase universally the prediction accuracy and the relative improvement over MTGBLUP reached up to 163.86% (25.64% on average).

Palladium catalyzed stereoselective intramolecular [3 + 2] cycloaddition reactions of (E) & (Z)-ene-vinylidenecyclopropanes.

A palladium-catalyzed ring-opening cyclization of (E) & (Z)-ene-vinylidenecyclopropanes has been developed via an intramolecular [3 + 2] cycloaddition process in the presence of a sterically bulky biaryl phosphine ligand, stereoselectively affording fused cis- & trans-bicyclo[4.3.0] skeletal products in good yields with a broad substrate scope and good functional tolerance. A plausible reaction mechanism was proposed on the basis of previous work and the DFT calculations.

Complete genome sequence and genetic characterization of a novel segmented RNA virus infecting Nilaparvata lugens.

The brown planthopper (BPH), Nilaparvata lugens, is a significant agricultural pest capable of long-distance migration and transmission of viruses that cause severe disease in rice. In this study, we identified a novel segmented RNA virus in a BPH, and this virus exhibited a close relationship to members of a recently discovered virus lineage known as "quenyaviruses" within the viral kingdom Orthornavirae. This newly identified virus was named "Nilaparvata lugens quenyavirus 1" (NLQV1). NLQV1 consists of five positive-sense, single-stranded RNAs, with each segment containing a single open reading frame (ORF). The genomic characteristics and phylogenetic analysis support the classification of NLQV1 as a novel quenyavirus. Notably, all of the genome segments of NLRV contained the 5'-terminal sequence AUCUG. The characteristic virus-derived small interfering RNA (vsiRNA) profile of NLQV1 suggests that the antiviral RNAi pathway of the host BPH was activated in response to virus infection. These findings represent the first documented report of quenyaviruses in planthoppers, contributing to our understanding of quenyaviruses and expanding our knowledge of insect-specific viruses in planthoppers.

Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity.

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.

ToxMPNN: A deep learning model for small molecule toxicity prediction.

Machine learning (ML) has shown a great promise in predicting toxicity of small molecules. However, the availability of data for such predictions is often limited. Because of the unsatisfactory performance of models trained on a single toxicity endpoint, we collected toxic small molecules with multiple toxicity endpoints from previous study. The dataset comprises 27 toxic endpoints categorized into seven toxicity classes, namely, carcinogenicity and mutagenicity, acute oral toxicity, respiratory toxicity, irritation and corrosion, cardiotoxicity, CYP450, and endocrine disruption. In addition, a binary classification Common-Toxicity task was added based on the aforementioned dataset. To improve the performance of the models, we added marketed drugs as negative samples. This study presents a toxicity predictive model, ToxMPNN, based on the message passing neural network (MPNN) architecture, aiming to predict the toxicity of small molecules. The results demonstrate that ToxMPNN outperforms other models in capturing toxic features within the molecular structure, resulting in more precise predictions with the ROC_AUC testing score of 0.886 for the Toxicity_drug dataset. Furthermore, it was observed that adding marketed drugs as negative samples not only improves the predictive performance of the binary classification Common-Toxicity task but also enhances the stability of the model prediction. It shows that the graph-based deep learning (DL) algorithms in this study can be used as a trustworthy and effective tool to assess small molecule toxicity in the development of new drugs.

Clinical research progress of novel antituberculosis drugs on multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has become a critical challenge to public health, and the prevention and treatment of MDR-TB are of great significance in reducing the global burden of tuberculosis. How to improve the effectiveness and safety of chemotherapy for MDR-TB is a pressing issue that needs to be addressed in tuberculosis control efforts. This article provides a comprehensive review of the clinical application of new antituberculosis drugs in MDR-TB, aiming to provide a scientific basis for the prevention and treatment strategy of MDR-TB.

A 3,000-year-old, basal S. enterica lineage from Bronze Age Xinjiang suggests spread along the Proto-Silk Road.

Salmonella enterica (S. enterica) has infected humans for a long time, but its evolutionary history and geographic spread across Eurasia is still poorly understood. Here, we screened for pathogen DNA in 14 ancient individuals from the Bronze Age Quanergou cemetery (XBQ), Xinjiang, China. In 6 individuals we detected S. enterica. We reconstructed S. enterica genomes from those individuals, which form a previously undetected phylogenetic branch basal to Paratyphi C, Typhisuis and Choleraesuis-the so-called Para C lineage. Based on pseudogene frequency, our analysis suggests that the ancient S. enterica strains were not host adapted. One genome, however, harbors the Salmonella pathogenicity island 7 (SPI-7), which is thought to be involved in (para)typhoid disease in humans. This offers first evidence that SPI-7 was acquired prior to the emergence of human-adapted Paratyphi C around 1,000 years ago. Altogether, our results show that Salmonella enterica infected humans in Eastern Eurasia at least 3,000 years ago, and provide the first ancient DNA evidence for the spread of a pathogen along the Proto-Silk Road.

Hydrophilic nanofibers with aligned topography modulate macrophage-mediated host responses via the NLRP3 inflammasome.

Successful biomaterial implantation requires appropriate immune responses. Macrophages are key mediators involved in this process. Currently, exploitation of the intrinsic properties of biomaterials to modulate macrophages and immune responses is appealing. In this study, we prepared hydrophilic nanofibers with an aligned topography by incorporating polyethylene glycol and polycaprolactone using axial electrospinning. We investigated the effect of the nanofibers on macrophage behavior and the underlying mechanisms. With the increase of hydrophilicity of aligned nanofibers, the inflammatory gene expression of macrophages adhering to them was downregulated, and M2 polarization was induced. We further presented clear evidence that the inflammasome NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was the cellular sensor by which macrophages sense the biomaterials, and it acted as a regulator of the macrophage-mediated response to foreign bodies and implant integration. In vivo, we showed that the fibers shaped the implant-related immune microenvironment and ameliorated peritendinous adhesions. In conclusion, our study demonstrated that hydrophilic aligned nanofibers exhibited better biocompatibility and immunological properties.

Mitogenome-wide association study on body measurement traits of Wenshang Barred chickens.

Mitochondria are best known for synthesizing ATP through the tricarboxylic acid cycle and oxidative phosphorylation. The cytoplasmic mitochondrial DNA (mtDNA) is important for maintaining the function. This study was designed to reveal the effect of mtDNA on chicken body measurement traits (BMTs). A population of 605 Wenshang Barred chickens were recorded BMTs, including body slope length, keel length, chest width, etc. The single-nucleotide polymorphisms (SNPs) of their mitogenomes were detected by PCR amplification and DNA sequencing. Totally 69 mutations in mitogenome were discovered, including 18 in noncoding region and 51 in coding region. By multi-sequence alignment and haplotype construction, the chickens were clustered into eight haplotypes and further three haplogroups. The association between BMTs and mtDNA SNPs, haplotypes and haplogroups were analyzed in the linear model by ASReml, respectively. Among them, the SNP mt11086 T/C in ND3 was found to significantly affect chest dept (p < .05) and was highly conservative by phylogenetic conservation analyses, which reflected the genetic effect on body size and growth of chickens. No significant association between the mitochondrial haplotypes or haplogroups and BMTs was found. The polymorphic site reflecting body size could be put into chicken breeding programs as the genetic marker.

Longitudinal genome-wide association studies of milk production traits in Holstein cattle using whole-genome sequence data imputed from medium-density chip data.

Longitudinal traits, such as milk production traits in dairy cattle, are featured by having phenotypic values at multiple time points, which change dynamically over time. In this study, we first imputed SNP chip (50-100K) data to whole-genome sequence (WGS) data in a Chinese Holstein population consisting of 6,470 cows. The imputation accuracies were 0.88 to 0.97 on average after quality control. We then performed longitudinal GWAS in this population based on a random regression test-day model using the imputed WGS data. The longitudinal GWAS revealed 16, 39, and 75 quantitative trait locus regions associated with milk yield, fat percentage, and protein percentage, respectively. We estimated the 95% confidence intervals (CI) for these quantitative trait locus regions using the logP drop method and identified 581 genes involved in these CI. Further, we focused on the CI that covered or overlapped with only 1 gene or the CI that contained an extremely significant top SNP. Twenty-eight candidate genes were identified in these CI. Most of them have been reported in the literature to be associated with milk production traits, such as DGAT1, HSF1, MGST1, GHR, ABCG2, ADCK5, and CSN1S1. Among the unreported novel genes, some also showed good potential as candidate genes, such as CCSER1, CUX2, SNTB1, RGS7, OSR2, and STK3, and are worth being further investigated. Our study provided not only new insights into the candidate genes for milk production traits, but also a general framework for longitudinal GWAS based on random regression test-day model using WGS data.

Mitochondrial DNA enrichment reduced NUMT contamination in porcine NGS analyses.

Genetic associations between mitochondrial DNA (mtDNA) and economic traits have been widely reported for pigs, which indicate the importance of mtDNA. However, studies on mtDNA heteroplasmy in pigs are rare. Next generation sequencing (NGS) methodologies have emerged as a promising genomic approach for detection of mitochondrial heteroplasmy. Due to the short reads, flexible bioinformatic analyses and the contamination of nuclear mitochondrial sequences (NUMTs), NGS was expected to increase false-positive detection of heteroplasmy. In this study, Sanger sequencing was performed as a gold standard to detect heteroplasmy with a detection sensitivity of 5% in pigs and then one whole-genome sequencing method (WGS) and two mtDNA enrichment sequencing methods (Capture and LongPCR) were carried out. The aim of this study was to determine whether mitochondrial heteroplasmy identification from NGS data was affected by NUMTs. We find that WGS generated more false intra-individual polymorphisms and less mapping specificity than the two enrichment sequencing methods, suggesting NUMTs indeed led to false-positive mitochondrial heteroplasmies from NGS data. In addition, to accurately detect mitochondrial diversity, three commonly used tools-SAMtools, VarScan and GATK-with different parameter values were compared. VarScan achieved the best specificity and sensitivity when considering the base alignment quality re-computation and the minimum variant frequency of 0.25. It also suggested bioinformatic workflow interfere in the identification of mtDNA SNPs. In conclusion, intra-individual polymorphism in pig mitochondria from NGS data was confused with NUMTs, and mtDNA-specific enrichment is essential before high-throughput sequencing in the detection of mitochondrial genome sequences.

GaSb surface grating distributed feedback interband cascade laser emitting at 3.25 µm.

A second-order distributed feedback interband cascade laser emitting at 3.25 µm was designed, grown, and fabricated. By coherent epitaxy of a GaSb cap layer instead of the conventional thin InAs cap on top of the laser structure, a high-quality surface grating was made of GaSb and gold. Enough coupling strength and a significant inter-modal loss difference were predicted according to the simulation within the framework of couple-wave theory. Lasers having 2-mm-long cavities and 4.5-µm-wide ridges with high-/anti-reflection coatings were fabricated. The continuous-wave threshold current and maximum single-mode output power were 60 mA and 24 mW at 20°C, respectively. The output power of 5 mW was still kept at 55°C. Continuous tuning free from mode hopping and high single-mode suppression ratios (>20 dB) were realized at all injection currents and heat-sink temperatures, covering a spectral range of over 20 cm-1.

Cost-effectively dissecting the genetic architecture of complex wool traits in rabbits by low-coverage sequencing.

BACKGROUND: Rabbit wool traits are important in fiber production and for model organism research on hair growth, but their genetic architecture remains obscure. In this study, we focused on wool characteristics in Angora rabbits, a breed well-known for the quality of its wool. Considering the cost to generate population-scale sequence data and the biased detection of variants using chip data, developing an effective genotyping strategy using low-coverage whole-genome sequencing (LCS) data is necessary to conduct genetic analyses. RESULTS: Different genotype imputation strategies (BaseVar + STITCH, Bcftools + Beagle4, and GATK + Beagle5), sequencing coverages (0.1X, 0.5X, 1.0X, 1.5X, and 2.0X), and sample sizes (100, 200, 300, 400, 500, and 600) were compared. Our results showed that using BaseVar + STITCH at a sequencing depth of 1.0X with a sample size larger than 300 resulted in the highest genotyping accuracy, with a genotype concordance higher than 98.8% and genotype accuracy higher than 0.97. We performed multivariate genome-wide association studies (GWAS), followed by conditional GWAS and estimation of the confidence intervals of quantitative trait loci (QTL) to investigate the genetic architecture of wool traits. Six QTL were detected, which explained 0.4 to 7.5% of the phenotypic variation. Gene-level mapping identified the fibroblast growth factor 10 (FGF10) gene as associated with fiber growth and diameter, which agrees with previous results from functional data analyses on the FGF gene family in other species, and is relevant for wool rabbit breeding. CONCLUSIONS: We suggest that LCS followed by imputation can be a cost-effective alternative to array and high-depth sequencing for assessing common variants. GWAS combined with LCS can identify new QTL and candidate genes that are associated with quantitative traits. This study provides a cost-effective and powerful method for investigating the genetic architecture of complex traits, which will be useful for genomic breeding applications.

Assessment of the performance of different imputation methods for low-coverage sequencing in Holstein cattle.

Low-coverage sequencing (LCS) followed by imputation has been proposed as a cost-effective genotyping approach for obtaining genotypes of whole-genome variants. Imputation performance is essential for the effectiveness of this approach. Several imputation methods have been proposed and successfully applied in genomic studies in human and other species. However, there are few reports on the performance of these methods in livestock. Here, we evaluated a variety of imputation methods, including Beagle v4.1, GeneImp v1.3, GLIMPSE v1.1.0, QUILT v1.0.0, Reveel, and STITCH v1.6.5, with varying sequencing depth, sample size, and reference panel size using LCS data of Holstein cattle. We found that all of these methods, except Reveel, performed well in most cases with an imputation accuracy over 0.9; on the whole, GLIMPSE, QUILT, and STITCH performed better than the other methods. For species with no reference panel available, STITCH followed by Beagle would be an optimal strategy, whereas for species with reference panel available, QUILT would be the method of choice. Overall, this study illustrated the promising potential of LCS for genomic analysis in livestock.

Breed-specific reference sequence optimized mapping accuracy of NGS analyses for pigs.

BACKGROUND: Reference sequences play a vital role in next-generation sequencing (NGS), impacting mapping quality during genome analyses. However, reference genomes usually do not represent the full range of genetic diversity of a species as a result of geographical divergence and independent demographic events of different populations. For the mitochondrial genome (mitogenome), which occurs in high copy numbers in cells and is strictly maternally inherited, an optimal reference sequence has the potential to make mitogenome alignment both more accurate and more efficient. In this study, we used three different types of reference sequences for mitogenome mapping, i.e., the commonly used reference sequence (CU-ref), the breed-specific reference sequence (BS-ref) and the sample-specific reference sequence (SS-ref), respectively, and compared the accuracy of mitogenome alignment and SNP calling among them, for the purpose of proposing the optimal reference sequence for mitochondrial DNA (mtDNA) analyses of specific populations RESULTS: Four pigs, representing three different breeds, were high-throughput sequenced, subsequently mapping reads to the reference sequences mentioned above, resulting in a largest mapping ratio and a deepest coverage without increased running time when aligning reads to a BS-ref. Next, single nucleotide polymorphism (SNP) calling was carried out by 18 detection strategies with the three tools SAMtools, VarScan and GATK with different parameters, using the bam results mapping to BS-ref. The results showed that all eighteen strategies achieved the same high specificity and sensitivity, which suggested a high accuracy of mitogenome alignment by the BS-ref because of a low requirement for SNP calling tools and parameter choices. CONCLUSIONS: This study showed that different reference sequences representing different genetic relationships to sample reads influenced mitogenome alignment, with the breed-specific reference sequences being optimal for mitogenome analyses, which provides a refined processing perspective for NGS data.

Rapid epistatic mixed-model association studies by controlling multiple polygenic effects.

SUMMARY: We have developed a rapid mixed model algorithm for exhaustive genome-wide epistatic association analysis by controlling multiple polygenic effects. Our model can simultaneously handle additive by additive epistasis, dominance by dominance epistasis and additive by dominance epistasis, and account for intrasubject fluctuations due to individuals with repeated records. Furthermore, we suggest a simple but efficient approximate algorithm, which allows the examination of all pairwise interactions in a remarkably fast manner of linear with population size. Simulation studies are performed to investigate the properties of REMMAX. Application to publicly available yeast and human data has showed that our mixed model-based method has similar performance with simple linear model on computational efficiency. It took less than 40 h for the pairwise analysis of 5000 individuals genotyped with roughly 350 000 SNPs with five threads on Intel Xeon E5 2.6 GHz CPU. AVAILABILITY AND IMPLEMENTATION: Source codes are freely available at https://github.com/chaoning/GMAT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Linc-KIAA1737-2 promoted LPS-induced HK-2 cell apoptosis by regulating miR-27a-3p/TLR4/NF-κB axis.

Inflammation and renal cell apoptosis participate in sepsis-induced acute kidney injury. Previous research found the upregulation of long non-coding RNA Linc-KIAA1737-2 in hypoxia- or inflammation-challenged human proximal tubular epithelial cells, but its role in sepsis-induced acute kidney injury is underexplored. In this research, we found that Linc-KIAA1737-2 could be upregulated in HK-2 human proximal tubular epithelial cells by LPS treatment, and knock-down of this lncRNA significantly attenuated LPS-induced apoptosis in HK-2 cells, while its overexpression showed opposite effect. MiR-27a-3p was confirmed to interact with Linc-KIAA1737-2 in HK-2 cells by RNA pull-down and dual-luciferase assay. MiR-27a-3p mimic transfection significantly attenuated LPS-induced HK-2 cell apoptosis by downregulating the protein levels of TLR4 and NF-κB, which was overturned by overexpression of Linc-KIAA1737-2. Our results suggested that Linc-KIAA1737-2 could promote LPS-induced apoptosis in HK-2 cells, and presumably sepsis-induced acute kidney injury, by regulating the miR-27a-3p/TLR4/NF-κB axis.

Identification and characteristics of insulin-like growth factor system in the brain, liver, and gonad during development of a seasonal breeding teleost, Pampus argenteus.

Reproductive activity is closely related to the development and function of the brain and liver in teleosts, particularly in seasonal breeding teleosts. This study measured the involvement of the insulin-like growth factor (IGF) system in controlling the reproduction of the silver pomfret Pampus argenteus, a seasonal breeding tropical to temperate commercial fish. We cloned and characterized the cDNAs of igfs (igf2 and igf3) and igfrs (igf1ra, igf1rb, and igf2r) and examined their transcript levels in relation to seasonal reproduction. Phylogenetic analyses revealed that two types of IGFs (IGF-1 and IGF-2) and three types of IGFRs (IGF1RA, IGF1RB, and IGF2R) of the silver pomfret were clustered with those of teleosts; however, IGF-3 was a transmembrane protein different with the IGF-3 of other teleosts. The expression of IGF-3 was gonad-specific in the silver pomfret. The transcript levels of igf1 in the female brain were the highest, and the levels of igfrs in both sexes' brains increased during gametogenesis. Meanwhile, igfs and igfrs maintained high transcript levels in both sexes' liver and gonad during vitellogenesis and spermatogonia proliferation. We concluded that the development and activities of brain, liver, and gonad were related to the IGF system (IGFs and IGFRs). And the IGFs were mainly expressed in the liver. Nevertheless, gonadal development, especially vitellogenesis and spermatogonia proliferation, were related with IGFs in this species.