Derivation of Arbas Cashmere Goat Induced Pluripotent Stem Cells in LCDM with Trophectoderm Lineage Differentiation and Interspecies Chimeric Abilities.

The Arbas cashmere goat is a unique biological resource that plays a vital role in livestock husbandry in China. LCDM is a medium with special small molecules (consisting of human LIF, CHIR99021, (S)-(+)-dimethindene maleate, and minocycline hydrochloride) for generation pluripotent stem cells (PSCs) with bidirectional developmental potential in mice, humans, pigs, and bovines. However, there is no report on whether LCDM can support for generation of PSCs with the same ability in Arbas cashmere goats. In this study, we applied LCDM to generate goat induced PSCs (giPSCs) from goat fetal fibroblasts (GFFs) by reprogramming. The derived giPSCs exhibited stem cell morphology, expressing pluripotent markers, and could differentiate into three germ layers. Moreover, the giPSCs differentiated into the trophectoderm lineage by spontaneous and directed differentiation in vitro. The giPSCs contributed to embryonic and extraembryonic tissue in preimplantation blastocysts and postimplantation chimeric embryos. RNA-sequencing analysis showed that the giPSCs were very close to goat embryos at the blastocyst stage and giPSCs have similar properties to typical extended PSCs (EPSCs). The establishment of giPSCs with LCDM provides a new way to generate PSCs from domestic animals and lays the foundation for basic and applied research in biology and agriculture.

Plant extracts in prevention of obesity.

Obesity has become a worldwide issue and is accompanied by serious complications. Western high energy diet has been identified to be a major factor contributing to the current obesity pandemic. Thus, it is important to optimize dietary composition, bioactive substances, and agents to prevent and treat obesity. To date, extracts from plants, such as vegetables, tea, fruits, and Chinese herbal medicine, have been showed to have the abilities of regulating adipogenesis and attenuating obesity. These plant extracts mainly contain polyphenols, alkaloids, and terpenoids, which could play a significant role in anti-obesity through various signaling pathways and gut microbiota. Those reported anti-obesity mechanisms mainly include inhibiting white adipose tissue growth and lipogenesis, promoting lipolysis, brown/beige adipose tissue development, and muscle thermogenesis. In this review, we summarize the plant extracts and their possible mechanisms responsible for their anti-obesity effects. Based on the current findings, dietary plant extracts and foods containing these bioactive compounds can be potential preventive or therapeutic agents for obesity and its related metabolic diseases.

Lipid Supplement in the Cultural Condition Facilitates the Porcine iPSC Derivation through cAMP/PKA/CREB Signal Pathway.

Large numbers of lipids exist in the porcine oocytes and early embryos and have the positive effects on their development, suggesting that the lipids may play an important role in pluripotency establishment and maintenance in pigs. However, the effects of lipids and their metabolites, such as fatty acids on reprogramming and the pluripotency gene expression of porcine-induced pluripotent stem cells (iPSCs), are unclear. Here, we generated the porcine iPSCs that resemble the mouse embryonic stem cells (ESCs) under lipid and fatty-acid-enriched cultural conditions (supplement of AlbuMAX). These porcine iPSCs show positive for the ESCs pluripotency markers and have the differentiation abilities to all three germ layers, and importantly, have the capability of aggregation into the inner cell mass (ICM) of porcine blastocysts. We further confirmed that lipid and fatty acid enriched condition can promote the cell proliferation and improve reprogramming efficiency by elevating cAMP levels. Interestingly, this lipids supplement promotes mesenchymal-epithelial transition (MET) through the cAMP/PKA/CREB signal pathway and upregulates the E-cadherin expression during porcine somatic cell reprogramming. The lipids supplement also makes a contribution to lipid droplets accumulation in the porcine iPSCs that resemble porcine preimplantation embryos. These findings may facilitate understanding of the lipid metabolism in porcine iPSCs and lay the foundation of bona fide porcine embryonic stem cell derivation.

SSRP1 Contributes to the Malignancy of Hepatocellular Carcinoma and Is Negatively Regulated by miR-497.

The aim of this study is to clarify the clinical implication and functional role of structure specific recognition protein 1 (SSRP1) in hepatocellular carcinoma (HCC) and explore the underlying mechanism of aberrant high expression of SSRP1 in cancers. In the present investigation, we validated that SSRP1 was upregulated in HCC samples. We also demonstrated that its upregulation was associated with several clinicopathologic features such as higher serum AFP level, larger tumor size, and higher T stage of HCC patients; and its high expression indicated shorter overall survival and faster recurrence. To investigate the role of SSRP1 in HCC progression, both loss- and gain-function models were established. We demonstrated that SSPR1 modulated both proliferation and metastasis of HCC cells in vitro and vivo. Furthermore, we demonstrated that SSRP1-modulated apoptosis process and its knockdown increased the sensitivity of HCC cells to doxorubicin, 5-Fluorouracil, and cisplatin. We also identified microRNA-497 (miR-497) as a posttranscriptional regulator of SSRP1. Ectopic expression of miR-497 inhibited 3'-untranslated-region-coupled luciferase activity and suppressed endogenous SSRP1 expression at both messenger RNA and protein levels. For the first time, we proved that SSRP1 upregulation contributed to HCC development and the tumor-suppressive miR-497 served as its negative regulator.

Three-Component Decomposition Based on Stokes Vector for Compact Polarimetric SAR.

In this paper, a three-component decomposition algorithm is proposed for processing compact polarimetric SAR images. By using the correspondence between the covariance matrix and the Stokes vector, three-component scattering models for CTLR and DCP modes are established. The explicit expression of decomposition results is then derived by setting the contribution of volume scattering as a free parameter. The degree of depolarization is taken as the upper bound of the free parameter, for the constraint that the weighting factor of each scattering component should be nonnegative. Several methods are investigated to estimate the free parameter suitable for decomposition. The feasibility of this algorithm is validated by AIRSAR data over San Francisco and RADARSAT-2 data over Flevoland.

Increased survival in hepatocellular carcinoma with iodine-125 implantation plus radiofrequency ablation: a prospective randomized controlled trial.

BACKGROUND & AIMS: The purpose of this study was to evaluate whether use of combined radiofrequency ablation (RFA) and percutaneous iodine-125 ((125)I) seed implantation results in better progression-free survival compared with the use of RFA alone in patients with hepatocellular carcinoma. METHODS: 136 patients were randomly assigned to undergo HCC treatment with RFA and percutaneous iodine-125 seed implantation (RFA-(125)I, n=68) or RFA-only (n=68). A total of 91 patients had hepatitis B viral infection in both groups. Rates of tumour recurrence and overall survival were evaluated. RESULTS: The probabilities of recurrence at 1-, 3-, and 5-years were 4.5%, 22.1%, and 39.8% in the RFA-(125)I group; and 14.8%, 35.3%, and 57.4% in the RFA-only group, respectively. The recurrence rate in the RFA-(125)I group was significantly lower than in the RFA-only group (HR, 0.508; 95% CI, 0.317-0.815; p=0.004 by log-rank test). Local and intrahepatic recurrence was significantly lower in the RFA-(125)I group than in the RFA-only group (7.3% vs. 22.0%, p=0.012 by log-rank test; 17.6% vs. 32.3%, p=0.041 by log-rank test). The probabilities of survival at 1-, 3-, and 5-years were 100%, 86.7%, and 66.1% in the RFA-(125)I group and 95.6%, 75.0%, and 47.0% in the RFA-only group, respectively. The survival rate in the RFA-(125)I group was significantly better than in the RFA-only group (HR, 0.502; 95% CI, 0.313-0.806; p=0.003 by log-rank test). Cox regression model indicated that the treatment group and tumour size were both recurrence-related and overall survival-related prognostic factors. CONCLUSIONS: There were significant differences in overall survival and cumulative recurrence between RFA-(125)I and RFA-only for patients with small HCCs (⩽3 cm). Treatment with RFA-(125)I facilitated better local and intrahepatic tumour control and long-term survival compared with treatment of RFA alone. ClinicalTrials.gov Identifier: NCT01717729.

Pig blastocyst-like structure models from embryonic stem cells.

Pluripotent stem cells have the potential to generate embryo models that can recapitulate developmental processes in vitro. Large animals such as pigs may also benefit from stem-cell-based embryo models for improving breeding. Here, we report the generation of blastoids from porcine embryonic stem cells (pESCs). We first develop a culture medium 4FIXY to derive pESCs. We develop a 3D two-step differentiation strategy to generate porcine blastoids from the pESCs. The resulting blastoids exhibit similar morphology, size, cell lineage composition, and single-cell transcriptome characteristics to blastocysts. These porcine blastoids survive and expand for more than two weeks in vitro under two different culture conditions. Large animal blastoids such as those derived from pESCs may enable in vitro modeling of early embryogenesis and improve livestock species' breeding practices.

Development of Bio-Voltage Operated Humidity-Sensory Neurons Comprising Self-Assembled Peptide Memristors.

Biomimetic humidity sensors offer a low-power approach for respiratory monitoring in early lung-disease diagnosis. However, balancing miniaturization and energy efficiency remains challenging. This study addresses this issue by introducing a bioinspired humidity-sensing neuron comprising a self-assembled peptide nanowire (NW) memristor with unique proton-coupled ion transport. The proposed neuron shows a low Ag+ activation energy owing to the NW and redox activity of the tyrosine (Tyr)-rich peptide in the system, facilitating ultralow electric-field-driven threshold switching and a high energy efficiency. Additionally, Ag+ migration in the system can be controlled by a proton source owing to the hydrophilic nature of the phenolic hydroxyl group in Tyr, enabling the humidity-based control of the conductance state of the memristor. Furthermore, a memristor-based neuromorphic perception neuron that can encode humidity signals into spikes is proposed. The spiking characteristics of this neuron can be modulated to emulate the strength-modulated spike-frequency characteristics of biological neurons. A three-layer spiking neural network with input neurons comprising these highly tunable humidity perception neurons shows an accuracy of 92.68% in lung-disease diagnosis. This study paves the way for developing bioinspired self-assembly strategies to construct neuromorphic perception systems, bridging the gap between artificial and biological sensing and processing paradigms.

Effects of Leymus chinensis hay and alfalfa hay on growth performance, rumen microbiota, and untargeted metabolomics of meat in lambs.

Objective: The objective of this study was to compare the effects of Leymus chinensis hay and alfalfa hay as the roughage on the rumen bacterial and the meat metabolomics in lambs. Methods: Fourteen male lambs were randomly assigned to two dietary treatments (one group was fed with concentrate and Leymus chinensis hay; another was fed with concentrate and alfalfa hay) with seven replicates per treatment. The feeding experiment lasted for 60 days. Lambs were slaughtered at the end of the feeding experiment. Growth performance, carcass performance, and weights of various viscera were determined. The longissimus dorsi and rumen contents were collected for untargeted metabolomics and 16S rDNA amplicon sequencing analysis, respectively. Results: The lambs fed with alfalfa hay showed a significantly increased in average daily gain, carcass weight, dressing percentage, loin-eye area, and kidney weight. Feeding Leymus chinensis hay and alfalfa hay diets resulted in different meat metabolite deposition and rumen bacterial communities in the lambs. The relative abundance of phyla Fibrobacteres, Bacteroidetes, and Spirochaetes were greater in the Leymus Chinensis hay group, while, the relative abundance of Firmicutes, Proteobacteria, Fusobacteria, and Verrucomicrobia were greater in the alfalfa hay group. Based on untargeted metabolomics, the main altered metabolic pathways included alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, phenylalanine metabolism, nitrogen metabolism, and tyrosine metabolism. Several bacteria genera including BF31, Alistipes, Faecalibacterium, Eggerthella, and Anaeroplasma were significantly correlated with growth performance and meat metabolites. Conclusion: Alfalfa hay improved growth performance and carcass characteristics in lambs. Leymus chinensis hay and alfalfa hay caused different meat metabolite deposition by modifying the rumen bacterial community. These findings will be beneficial to future forage utilization for sheep growth, carcass performance, and meat quality improvement.

Construction and validation of an oxidative-stress-related risk model for predicting the prognosis of osteosarcoma.

BACKGROUND: Osteosarcoma is the most common bone malignancy in teenagers, and warrants effective measures for diagnosis and prognosis. Oxidative stress (OS) is the key driver of several cancers and other diseases. METHODS: The TARGET-osteosarcoma database was employed as the training cohort and GSE21257 and GSE39055 was applied for external validation. The patients were classified into the high- and low-risk groups based on the median risk score of each sample. ESTIMATE and CIBERSORT were applied for the evaluation of tumor microenvironment immune infiltration. GSE162454 of single-cell sequencing was employed for analyzing OS-related genes. RESULTS: Based on the gene expression and clinical data of 86 osteosarcoma patients in the TARGET database, we identified eight OS-related genes, including MAP3K5, G6PD, HMOX1, ATF4, ACADVL, MAPK1, MAPK10, and INS. In both the training and validation sets, the overall survival of patients in the high-risk group was significantly worse than that in the low-risk group. The ESTIMATE algorithm revealed that patients in the high-risk group had higher tumor purity but lower immune score and stromal score. In addition, the CIBERSORT algorithm showed that the M0 and M2 macrophages were the predominant infiltrating cells in osteosarcoma. Based on the expression analysis of immune checkpoint, CD274(PDL1), CXCL12, BTN3A1, LAG3, and IL10 were identified as potential immune therapy targets. Analysis of the single cell sequencing data also revealed the expression patterns of OS-related genes in different cell types. CONCLUSIONS: An OS-related prognostic model can accurately provide the prognosis of osteosarcoma patients, and may help identify suitable candidates for immunotherapy.

[Retracted] SIRT1 promotes tumorigenesis of hepatocellular carcinoma through PI3K/PTEN/AKT signaling.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control ß­actin western blots shown in Figs. 1B and 6 were strikingly similar to data that had already appeared in a different form in the following publication: Lei Y, Liu H, Yang Y, Wang X, Ren N, Li B, Liu S, Cheng J, Fu X and Zhang J: Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV­induced hepatocellular carcinoma. Oncol Rep 29: 151­159, 2012. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 28: 311­318, 2012; DOI: 10.3892/or.2012.1788].

[Corrigendum] Crocetin induces apoptosis of BGC­823 human gastric cancer cells.

Following the publication of the above article, an interested reader drew to the authors' attention that Fig. 2 (showing morphological characteristics of cultured BGC­823 cells as visualized by microscopic analysis) and Fig. 3 (showing crocetin­induced apoptosis of the BGC­823 cells) on p. 523 appeared to feature panels containing overlapping data. The authors re­examined their original data, and realized that inadvertent errors were made during the compilation of these figures; specifically, the data shown in Fig. 2C (for the the 5­µM docetaxel group) and Fig. 3D (for the DMSO group) were selected incorrectly. The corrected versions of Figs. 2 and 3 are shown below and on the next page, now featuring the correct data for Figs. 2C and 3D. All the authors agree with the publication of this corrigendum, and are grateful of the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. Furthermore, they regret that these errors were introduced into the paper, even though they did not substantially alter any of the major conclusions reported in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 9: 521­526, 2014; DOI: 10.3892/mmr.2013.1851].

The effect of reverse intergenerational support on the happiness of Chinese older adults: A moderating effect analysis based on role conflict.

Intergenerational support is bidirectional, and reverse intergenerational support refers to parents providing financial support, time support, and spiritual support to their offspring. The emergence of reverse intergenerational support has created role conflicts among different groups of older adults. Based on survey data from 3,170 elderly people in eight sample provinces in China, this paper empirically investigates the relationship between reverse intergenerational support and the happiness of the elderly in contemporary China and the moderating effect of role conflict in it, using an ordered logit model. It was found that, first, reverse economic support reduces the happiness of the elderly, and reverse time support and reverse spiritual support can significantly enhance the happiness of the elderly. Second, in the presence of role conflict, the effect of reverse time support and reverse spiritual support on the enhancement of older adults' happiness was suppressed; in the presence of role enhancement, the effect of reverse economic support on the reduction of older adults' happiness was mitigated. The above findings provide new empirical evidence for understanding the relationship between reverse intergenerational support and the happiness of the elderly, which is prevalent in contemporary China, and offer new insights for enhancing happiness.

Carbon Mitigation Pathways of Urban Transportation under Cold Climatic Conditions.

Climate heterogeneity has enormous impacts on CO2 emissions of the transportation sector, especially in cold regions where the demand for in-car heating and anti-skid measures leads to high energy consumption, and the penetration rate of electric vehicles is low. It entails to propose targeted emission reduction measures in cold regions for peaking CO2 emissions as soon as possible. This paper constructs an integrated long-range energy alternatives planning system (LEAP) model that incorporates multi-transportation modes and multi-energy types to predict the CO2 emission trend of the urban transportation sector in a typical cold province of China. Five scenarios are set based on distinct level emission control for simulating the future trends during 2017-2050. The results indicate that the peak value is 704.7-742.1 thousand metric tons (TMT), and the peak time is 2023-2035. Energy-saving-low-carbon scenario (ELS) is the optimal scenario with the peak value of 716.6 TMT in 2028. Energy intensity plays a dominant role in increasing CO2 emissions of the urban transportation sector. Under ELS, CO2 emissions can be reduced by 68.66%, 6.56% and 1.38% through decreasing energy intensity, increasing the proportion of public transportation and reducing the proportion of fossil fuels, respectively. Simultaneously, this study provides practical reference for other cold regions to formulate CO2 reduction roadmaps.

MiR-132-3p inhibits proliferation, invasion and migration of colorectal cancer cells via down-regulating FOXP2 expression.

OBJECTIVE: colorectal cancer (CRC) is a common cancer with high mortality. This study aimed to investigate the role of microRNA (miR)-132-3p on proliferation, invasion and migration of CRC cells. MATERIALS AND METHODS: qRT-PCR and Western blot analyses were used to determine the expression of miR-132-3p and forking box (FOX) protein 2 (FOXP2) in CRC cell line CACO-2. The expression of miR-132-3p and FOX was regulated using miR inhibitor and siRNA, and the viability and migration ability of the transfected cells were assessed. Cell cycle dependent kinase (CDK) 1, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-9 were detected using Western blots. The dual luciferase reporter gene assays were used to verify the targeting of miR-132-3p to FOXP2. RESULTS: Compared with control cells, FOXP2 and miR-132-3p expressions were decreased or increased significantly (P<0.05), respectively in CACO-2 cells. Up-regulation of miR-132-3p effectively inhibited the proliferation, migration and invasion of CACO-2 cells, and suppressed the expression of FORX2, cyclin-dependent kinase 1 (CDK1), cyclin D1, MMP-2 and MMP-9. Luciferase reporter gene assays reveled that FOXP2 expression was negatively regulated by miR-132-3p. Knockdown of FOXP2 using siRNA significantly reduced the proliferation and migration of CACO-2 cells, down-regulated the expression FOXP2 as well as CDK1, cyclin D1, MMP-2 and MMP-9. Since FOXP2 is targeted by miR-132-3p, it is likely that miR-132-3p-mediated reduction of proliferation and migration of CACO-2 cells was achieved via reduced translation of FOXP2 mRNA. CONCLUSIONS: miR-132-3p inhibits the proliferation, migration and invasion of CRC cells. This is likely achieved via negative regulation of the targeted FOXP2 expression. This role may be further explored for therapeutic applications in CRC.

A comparative analysis of carcass and meat traits, and rumen bacteria between Chinese Mongolian sheep and Dorper × Chinese Mongolian crossbred sheep.

Mutton is one of the most widely consumed meats globally. The Chinese Mongolian sheep (MS) breed is an indigenous breed of sheep characterised by high-quality meat and strong adaptability. Dorper × Chinese Mongolian crossbred sheep (DS) is an improved breed with a rapid growth rate and high mutton yield found in parts of China. The rumen microbiota is known to play a key role in shaping host nutrition and health. However, the carcass traits and meat nutritional qualities of DS and MS remain poorly defined, as does how rumen microbes affect these characteristics. The objective of this study was to compare carcass profiles, rumen bacterial communities, and meat nutritional qualities between MS and DS and clarify the associations between rumen microbiota and meat nutritional composition. We found that DS had a faster growth rate and better carcass traits than MS, including BW, carcass weight, meat weight, and loin-eye area. We further found that metabolite and rumen bacterial community composition differed between the two sheep breeds. First, compared with MS, DS had lower contents of some sweet amino acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, and beneficial metabolites. Secondly, MS and DS had distinct rumen bacterial compositions, and these differential bacteria were related to carcass traits as well as to contents of meat amino acids, free fatty acids, and other metabolites. Taken together, our data showed that DS had better carcass characteristics but lower meat nutritional quality, parameters that were associated with differences in rumen bacterial community composition. These findings may benefit future breeding strategies aimed at improving sheep carcass performance and meat quality worldwide.

Changes of Intestinal Microflora in Colorectal Cancer Patients after Surgical Resection and Chemotherapy.

OBJECTIVE: The change of bacterial flora structure in colorectal cancer (CRC) patients after treatment is not clear. The aim of this study was to explore the change and function of intestinal microflora in CRC before and after treatment. METHOD: The 16S conserved region V3+V4 of intestinal flora obtained from CRC patients was sequenced and analyzed. Alpha and beta diversity indices were used to analyze the abundance and structure of gut flora. FAPROTAX, BugBase, and Tax4Fun software were used to analyze the species phenotypes and Kyoto Encyclopedia of Genes and Genomes Ontology (KO) function pathways. RESULTS: Total abundance and structure of species in CRC patients were significantly increased compared with healthy people (control group) (P < 0.05), but there was no significant difference between CRC patients before and after treatment (P > 0.05). There was significant difference in relative abundance of bacteria at different levels (phylum, class, order, family, genus, and species) between the CRC group with after operation (CRC_O group) and chemotherapy (CRC_C group) treatment, particularly Prevotellaceae_UCG-001, Akkermansia, Fusicatenibacter, Tyzzerella_4, Megamonas, etc. in genus level. The KO function analysis showed that most of the bacteria with differences were mainly involved in the biosynthesis of lipopolysaccharide (Megamonas, Megasphaera, and Ruminococcus torques_group), protein digestion and absorption, renin-angiotensin system pathway (Akkermansia, Eubacterium_ruminantium_group, and Eubacterium_nodatum_group genus), adipocytokine signaling pathway and peroxisome pathway (Tyzzerella_4, Phascolarctobacterium, Ruminococcus_gnavus_group), and so on. CONCLUSION: The abundance of intestinal microflora in CRC patients was increased significantly contrasted to healthy people, and surgery and chemotherapy were hard to reduce this phenomenon. Megamonas was involved in lipopolysaccharide biosynthesis and carcinogenesis in colorectal cancer. Surgery and drug treatment did not reduced lipopolysaccharide biosynthesis but increased the number of probiotic Akkermansia population and reduced the pathogenic bacteria Tyzzerella_4, participate in adipocytokine signaling pathway, and affect metabolism.

Whole-genome resequencing reveals domestication and signatures of selection in Ujimqin, Sunit, and Wu Ranke Mongolian sheep breeds.

OBJECTIVE: The current study aimed to perform whole-genome resequencing of Chinese indigenous Mongolian sheep breeds including Ujimqin, Sunit, and Wu Ranke sheep breeds (UJMQ, SNT, WRK) and deeply analyze genetic variation, population structure, domestication, and selection for domestication traits among these Mongolian sheep breeds. METHODS: Blood samples were collected from a total of 60 individuals comprising 20 WRK, 20 UJMQ, and 20 SNT. For genome sequencing, about 1.5 µg of genomic DNA was used for library construction with an insert size of about 350 bp. Pair-end sequencing were performed on Illumina NovaSeq platform, with the read length of 150 bp at each end. We then investigated the domestication and signatures of selection in these sheep breeds. RESULTS: According to the population and demographic analyses, WRK and SNT populations were very similar, which were different from UJMQ populations. Genome wide association study identified 468 and 779 significant loci from SNT vs UJMQ, and UJMQ vs WRK, respectively. However, only 3 loci were identified from SNT vs WRK. Genomic comparison and selective sweep analysis among these sheep breeds suggested that genes associated with regulation of secretion, metabolic pathways including estrogen metabolism and amino acid metabolism, and neuron development have undergone strong selection during domestication. CONCLUSION: Our findings will facilitate the understanding of Chinese indigenous Mongolian sheep breeds domestication and selection for complex traits and provide a valuable genomic resource for future studies of sheep and other domestic animal breeding.

LCDM medium supports the derivation of bovine extended pluripotent stem cells with embryonic and extraembryonic potency in bovine-mouse chimeras from iPSCs and bovine fetal fibroblasts.

Cattle have emerged as one of the most important domestic animals widely used for meat, milk, and fur. Derivation of bovine pluripotent stem cells (PSCs) can be applied in drug selecting and human disease modeling and facilitated agriculture-related applications such as production of genetically excellent cattle by gene editing. Extended PSCs (EPSCs), capable of differentiating into embryonic and extraembryonic parts, have been generated in mouse, human, and pig. Whether bovine EPSCs could be generated, and their chimeric competency remains unclear. This study focused on derivation of bovine EPSCs using LCDM medium and exploring the characteristics of EPSCs among different species, including bovine, mouse, and human EPSCs. Here, using LCDM medium (consisting of hLIF, CHIR99021, (S)-(+)-dimethindene maleate, and minocycline hydrochloride) enables the derivation of bovine EPSCs from induced PSCs (iPSCs) and bovine fetal fibroblasts (BFF) with stable morphology, pluripotent marker expression, and in vitro differentiation ability. Notably, bovine EPSCs exhibited interspecies chimeric contribution to embryonic and extraembryonic tissues in pre-implantation blastocysts and postimplantation bovine-mouse chimeras. Transcriptome analysis revealed the unique molecular characteristics of bovine EPSCs compared with iPSCs. The similarities and differences in molecular features across bovine, human, and mouse EPSCs were also described by transcriptome analysis. Taken together, the LCDM culture system containing chemical cocktails can be used for the establishment and long-term passaging of bovine EPSCs with embryonic and extraembryonic potency in bovine-mouse chimeras. Our findings lay the foundation of generating PSCs in domestic animals and open avenues for basic and applied research in biology, medicine, and agriculture. DATABASE: Gene expression data of bovine EPSCs and bovine iPSCs are available in the GEO databases under the accession number PRJNA693452.

Milk fat globule membrane and its component phosphatidylcholine induce adipose browning both in vivo and in vitro.

The functional induction of brown-like adipocytes in white adipose tissue (WAT) provides a defense against obesity. The aim of this study was to analyze the effects of milk fat globule membrane (MFGM) and its component phosphatidylcholine (PC) on the brown remodeling of WAT. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks and then fed HFD for another 8 weeks with MFGM. In vitro studies were performed in C3H10T1/2 pluripotent stem cells, 3T3-L1 pre-adipocytes and differentiated inguinal WAT stromal vascular cells (SVCs) to determine the role of MFGM and PC on the formation of brown-like adipocytes. MFGM decreased fasting glucose and serum insulin levels in HFD-fed mice. MFGM improved glucose tolerance and insulin sensitivity, and induced browning of inguinal WAT. MFGM and its component PC stimulated transformation of brown-like adipocytes in C3H10T1/2 pluripotent stem cells, 3T3-L1 adipocytes and SVCs by increasing the protein expression of UCP1, PGC-1α, PRDM16 as well as the mRNA expression of other thermogenic genes and beige cell markers. MFGM and PC also increased mitochondrial DNA (mtDNA) copy number, mitochondrial density and oxygen consumption rate and up-regulated the mRNA expression of mitochondria-biogenesis-related genes in vitro. PPARα inhibitor GW6471 treatment or knockdown of PPARα using lentivirus-expressing shRNA inhibited the PC-induced increase in the protein expression of UCP1, PGC-1α and PRDM16 in C3H10T1/2 pluripotent stem cells and 3T3-L1 adipocytes, indicating the potential role of PPARα in PC-mediated brown-like adipocyte formation. In conclusion, MFGM and milk PC induced adipose browning, which has major protective effects against obesity and metabolic dysfunction.