As a malignancy of the gastrointestinal tract, gallbladder cancer (GBC) continues to exhibit notable rates of mortality. The current study aimed at investigating the effects associated with miR-30b ...and miR-30d (miR-30b/-30d) patterns in tumor cells undergoing epithelial-to-mesenchymal transition (EMT) in GBC. It identified that miR-30b and miR-30d, composed as a miRNA cluster, exhibited lower levels in the cancerous tissues from 50 patients with GBC relative to the gallbladder tissues from 35 patients with chronic cholecystitis. As expected, elevated expression of miR-30b/-30d was found to inhibit the EMT process, as evidenced by enhanced E-cadherin and reduced N-cadherin and vimentin in human GBC cells treated with miR-30b mimic, miR-30d mimic, and miR-30b/-30d mimic. Semaphorin-6B (SEMA6B) was identified as a target gene of miR-30b/-30d. Silencing of SEMA6B by its specific small interfering RNA (siRNA) mimicked the effect of miR-30b/-30d upregulation on the GBC cell EMT. Consistently, SEMA6B overexpression promoted this phenotypic switch even in the presence of miR-30b/-30d mimic. The tumorigenicity assay data obtained from nude mice also further supported the notion that miR-30b/-30d inhibited EMT of GBC cells. Thus, based on the key findings of the current study, we concluded that the miR-30b/-30d cluster may provide a potential avenue for targeting mesenchymal-like, invasive tumor cells in GBC.
Display omitted
Overexpression of miR-30b/-30d inhibits GBC cell migration, invasion, and EMT process in vitro as well as delays the tumorigenesis of GBC cells in vivo by targeting SEMA6B. By this mechanism, miR-30b/-30d prevents the progression of GBC.
Objective Observing and analyzing the delivery behaviour of cynomolgus macaques, to establish the criteria for determining the occurrence of delivery in cynomolgus macaques, and then combining with ...veterinary assistance in order to improve the live birth rate of cynomolgus macaques.Methods By backtracking and analyzing the surveillance videos of 112 perinatal cynomolgus macaques with a gestation period of 140 d or more from 2017 to 2021, we observed and recorded the main behavioural manifestations of the cynomolgus macaques during labour, including Valsalva's maneuver, touching and licking the birth canal, lying on their backs or stomachs, and rolling and tumbling of the body. On this basis, we established the weights of delivery-related behavioural indicators and exhaustively analysed the perinatal behavioural performances of 30 cynomolgus macaques for delivery determination.Results The perinatal behavioural validation results of the 30 cynomolgus macaques showed that the behavioural indicators of Valsalva's
Embryo development after fertilization is largely determined by the oocyte quality, which is in turn dependent on the competence of both the cytoplasm and nucleus. Here, to improve the efficiency of ...embryo development from developmentally incompetent oocytes, we performed spindle-chromosome complex transfer (ST) between in vitro matured (IVM) and in vivo matured (IVO) oocytes of the non-human primate rhesus monkey. We observed that the blastocyst rate of embryos derived from transferring the spindle-chromosome complex (SCC) of IVM oocytes into enucleated IVO oocytes was comparable with that of embryos derived from IVO oocytes. After transferring the reconstructed embryos into the uterus of surrogate mothers, two live rhesus monkeys were obtained, indicating that the nuclei of IVM oocytes support both the pre-and post-implantation embryo development of non-human primates.
Display omitted
•Spindle-chromosome complex transfer improves cytoplasmic quality of primate oocytes•In vitro matured oocyte nuclei support pre- and post-implantation embryo development•Live rhesus monkeys were obtained by nucleus transferred of in vitro matured oocyte
Reproductive medicine; Female reproductive endocrinology; Cell biology
Simian retrovirus subtype 8 (SRV-8) infections have been reported in cynomolgus monkeys (
) in China and America, but its pathogenicity and immunogenicity are rarely reported. In this work, the ...SRV-8-infected monkeys were identified from the monkeys with anemia, weight loss, and diarrhea. To clarify the impact of SRV-8 infection on cynomolgus monkeys, infected monkeys were divided into five groups according to disease progression. Hematoxylin (HE) staining and viral loads analysis showed that SRV-8 mainly persisted in the intestine and spleen, causing tissue damage. Additionally, the dynamic variations of blood routine indexes, innate and adaptive immunity, and the transcriptomic changes in peripheral blood cells were analyzed during SRV-8 infection. Compared to uninfected animals, red blood cells, hemoglobin, and white blood cells were reduced in SRV-8-infected monkeys. The percentage of immune cell populations was changed after SRV-8 infection. Furthermore, the number of hematopoietic stem cells decreased significantly during the early stages of SRV-8 infection, and returned to normal levels after antibody-mediated viral clearance. Finally, global transcriptomic analysis in PBMCs from SRV-8-infected monkeys revealed distinct gene expression profiles across different disease stages. In summary, SRV-8 infection can cause severe pathogenicity and immune disturbance in cynomolgus monkeys, and it might be responsible for fatal virus-associated immunosuppressive syndrome.
Abstract
Cloning of macaque monkeys by somatic cell nucleus transfer (SCNT) allows the generation of monkeys with uniform genetic backgrounds that are useful for the development of non-human primate ...models of human diseases. Here, we report the feasibility of this approach by SCNT of fibroblasts from a macaque monkey (Macaca fascicularis), in which a core circadian transcription factor BMAL1 was knocked out by clustered regularly interspaced short palindromic repeat/Cas9 gene editing (see accompanying paper). Out of 325 SCNT embryos transferred into 65 surrogate monkeys, we cloned five macaque monkeys with BMAL1 mutations in both alleles without mosaicism, with nuclear genes identical to that of the fibroblast donor monkey. Further peripheral blood mRNA analysis confirmed the complete absence of the wild-type BMAL1 transcript. This study demonstrates that the SCNT approach could be used to generate cloned monkeys from fibroblasts of a young adult monkeys and paves the way for the development of macaque monkey disease models with uniform genetic backgrounds.
Genomic imprinting can lead to allele-specific expression (ASE), where one allele is preferentially expressed more than the other. Perturbations in genomic imprinting or ASE genes have been widely ...observed across various neurological disorders, notably autism spectrum disorder (ASD). In this study, we crossed rhesus cynomolgus monkeys to produce hybrid monkeys and established a framework to evaluate their allele-specific gene expression patterns using the parental genomes as a reference. Our proof-of-concept analysis of the hybrid monkeys identified 353 genes with allele-biased expression in the brain, enabling us to determine the chromosomal locations of ASE clusters. Importantly, we confirmed a significant enrichment of ASE genes associated with neuropsychiatric disorders, including ASD, highlighting the potential of hybrid monkey models in advancing our understanding of genomic imprinting.
Display omitted
•Cynomolgus-rhesus hybrid macaques is a powerful platform to investigate imprinting.•Location information of ASE genes can be obtained using hybrid strategy.•Identification of ASE genes benefits understanding the association between imprinting and neuropsychiatric disorders.
Purpose
The purpose of this study is to prolong the service life of the Al–Si alloy cylinder and achieve the objective of energy saving and emission reduction by the composite treatments.
...Design/methodology/approach
Chemical etching + laser texturing + filled MoS2 composite treatment was applied to the friction surface of aluminum–silicon (Al–Si) alloy cylinder. The friction coefficient and wear loss were measured to characterize the tribology property of cylinders.
Findings
The composite-treated Al–Si alloy cylinder had the lowest friction coefficient and weight loss. The friction coefficient and weight loss of the composite treatment were approximately 27.08% and 54.17% lower than those of the untreated sample, respectively. The laser micro-textures control the release of solid lubricant to the interface of friction pairs slowly, which prolongs the service life of cylinders.
Originality/value
The synergistic effect of the chemical etching + laser texturing + filled MoS2 modified the tribology properties of Al–Si alloy cylinder. The chemical etching raised the silicon particles to bear the load, and laser micro-textures control the release of solid lubricant to improve the lubrication property.
Human stem cell-derived blastoids display similar morphology and cell lineages to normal blastocysts. However, the ability to investigate their developmental potential is limited. Here, we construct ...cynomolgus monkey blastoids resembling blastocysts in morphology and transcriptomics using naive ESCs. These blastoids develop to embryonic disk with the structures of yolk sac, chorionic cavity, amnion cavity, primitive streak, and connecting stalk along the rostral-caudal axis through prolonged in vitro culture (IVC). Primordial germ cells, gastrulating cells, visceral endoderm/yolk sac endoderm, three germ layers, and hemato-endothelial progenitors in IVC cynomolgus monkey blastoids were observed by single-cell transcriptomics or immunostaining. Moreover, transferring cynomolgus monkey blastoids to surrogates achieves pregnancies, as indicated by progesterone levels and presence of early gestation sacs. Our results reveal the capacity of in vitro gastrulation and in vivo early pregnancy of cynomolgus monkey blastoids, providing a useful system to dissect primate embryonic development without the same ethical concerns and access challenges in human embryo study.
Display omitted
•Generation of cynomolgus monkey blastoids using naive ESCs and optimized protocol•Monkey blastoids showed similar morphology and lineage composition to blastocysts•In vitro cultured monkey blastoids recapitulate gastrulation to three germ layers•In vivo transplantation of monkey blastoids triggers pregnancy with gestation sacs
Stem cell-based embryo models provide a useful system for studying early embryonic development. Li and colleagues reported the generation of cynomolgus monkey blastoids with similar characteristics to natural blastocysts. These blastoids possess the capacity of in vitro gastrulation with three germ-layer differentiation and in vivo early pregnancy with gestation sac.
Presynaptic syntaxin binding protein 1 (STXBP1) is essential for neurotransmitter release. Heterozygous mutations in this protein cause STXBP1 encephalopathy (STXBP1-E), which is characterized by ...intellectual disabilities and epilepsies. Since nonhuman primates closely resemble humans, monkey models may advance studies on the pathogenesis and therapeutic treatments of STXBP1-E. We generated cynomolgus monkeys carrying STXBP1 (R292H) mutation through base editing of in vitro fertilized embryos to mimic a clinical condition. The newborn STXBP1-edited monkeys exhibited focal epilepsy, and the animal that survived beyond the first week postpartum presented typical EEG phenotypes. Biochemical analysis of brain biopsy samples showed reduced levels of STXBP1 (MUNC18-1) and SNARE complex proteins. Single-cell sequencing identified one specific cell cluster that may contribute to encephalopathy. Thus, our case report shows that base-edited STXBP1 mutant monkeys are a good animal model for STXBP1-E, and that a base-editing approach is useful for generating primate models of human genetic disorders.
Display omitted
In this study, we generated cynomolgus monkeys carrying STXBP1 (R292H) mutation through base editing to mimic a clinical condition. The newborn STXBP1-edited monkeys exhibited focal epilepsy, especially typical EEG phenotypes. Biochemical analysis and single-cell sequencing showed dysregulation of proteins and cell type. Thus, our study reports a promising animal model for STXBP1-E.
PDF
