As a potent insulinotrophic hormone, glucagon-like peptide 1 (GLP-1) is mainly secreted by intestinal L cells, which can effectively promote the release of insulin and thus reduce blood glucose. Therefore, GLP-1 and its analogs have a good prospect in the treatment of type 2 diabetes. In this study, we constructed mouse intestinal organoids that overexpress GLP-1 by optimizing the GLP-1 lentivirus infection method. We found that supernatants secreted by the GLP-1 overexpression organoids effectively enhanced glucose tolerance in wild-type and diabetic mouse. Thus, the GLP-1 overexpression organoids built in this study may provide a novel strategy for the treatment of type 2 diabetes.

Zi Cao is an important traditional medicinal plant resource in China. Shikonin and its derivatives, as the purple-red naphthoquinones among natural products of its roots, are commonly used clinically in the treatment of sores and skin inflammations. Over the past few decades, due to their highly effective multiple biological activities, pharmacological effects, good clinical efficacy and high utilization value, shikonin and its derivatives have attracted increasing attention of domestic and foreign researchers. For this reason, the wild plant germplasm resources have been suffering a grievous exploitation, leading to a serious threat to the habitat. With the development of the biosynthesis, molecular metabolism and biotechnology, as well as the continuous innovation of research methods on the biological activities and pharmacological effects of plant natural products, significant progress has been made in the research on the biosynthetic pathways and related regulatory genes of shikonin. The pharmacological action and its mechanism of shikonin have also been deeply elucidated, which greatly promoted the basic research and clinical application development of shikonin. In this review, we briefly introduce and analyze the classification of Zi Cao, structure and composition of natural shikonin and its biosynthesis pathway, functional genes related to the regulation of shikonin biosynthesis, and biological activities and pharmacological functions of shikonin. Finally, we address possible prospective for the trend on the future research and development of natural shikonin and its derivatives, hoping to provide a useful reference for the deep mining and development of medicinal natural products from important Chinese medicinal materials, and to promote the modern development of traditional Chinese medicine.

Autism spectrum disorder is a group of genetically-related developmental disorders of the nervous system. Patients mainly present with core symptoms such as social behavior defects, repetitive stereotyped behaviors, and learning and memory disorders. The mouse models are critical for the studies of the pathogenic mechanisms and potential therapeutic strategies of autism spectrum disorder. The assessments of mouse behaviors provide understandings of the effects of different genetic manipulations as well as pathogenic mechanisms of these diseases. This article describes various mouse behavioral assays corresponding to the core symptoms of ASD patients and provides a detailed description of protocols, cautions, and data analysis for those assays, thereby helping researchers to establish their own experimental designs. In addition, behavioral phenotypes of currently known ASD mouse models are summarized to provide a reference for researchers in the field.

Mouse Developmental and Metabolic Phenotype Repository (MDMPR) is an open access, real-time database which dedicates to share mouse resources and phenotype data. MDMPR is supported by the National Key Research and Development Project "Establishment of Mouse Developmental and Metabolic Phenotype Repository" within the Key Project of "Developmental Programming and Its Metabolic Regulation" from the Ministry of Science and Technology of the People's Republic of China's program. In the next 5 years, MDMPR will create 500 mutant mouse models related to development and metabolism, perform standard phenotyping analysis, and establish a phenotype database. MDMPR is a combination of resources and data repository, has several sub-systems, including the ES cell database, the project management system, the breeding management system, the sperm bank management system and the phenotyping database. These systems digitalize all data and ensure their authenticity in real-time. Besides the gradual increase of data during the project, MDMPR will also integrate other resources, such as human KO ES cell database, STRING database, database of Core Transcriptional Regulatory Circuitries and Enhancer-Indel database. MDMPR is anticipated to contribute to various areas of developmental and metabolic research to investigators through more convenient accesses to the resources and data in one-stop manner, thereby accelerating the research processes and ultimately serving the medical causes of human health.

The accuracy of genetic evaluations in different herds is affected by the degree of genetic connectedness among herds. In this study, we explored the application of high density SNP markers in the assessment of genetic connectedness by comparing the genetic connectedness based on pedigree data and genomic data. Six methods, including PEVD (prediction error variance of differences between estimated breeding values), PEVD (x), VED (variance of estimated difference between the herd effects), CD (generalized coefficient of determination), r (prediction error correlation) and CR (connectedness rating), were implemented to measure the genetic connectedness based on different relationship matrices (A, G, Gs, G0. 5 and H). Our results from both simulated data and SNP chip data indicated that, except for the PEVD (x) and VED methods, the genetic connectedness obtained by PEVD, CD, r and CR based on G. Gs and G0.5 matrices (using genome information only) were superior to those based on A matrix (using pedigree information only). Generally, for most approaches, the genetic connectedness based on H matrix (using both pedigree and genome information) was somewhere between A matrix and G matrices. CD could overestimate the degree of genetic connectedness as it was still very high when CR and r were close to 0. The method r could not accurately reflect the true genetic connectedness of the populations. It generated 0.01 of genetic connectedness for all three pig breeding farms, which were actually genetically different with each other. With increasing of heritability, the degree of genetic connectedness obtained by all methods were increased as well. However, in the case of heritability 0.1, PEVD based on A matrix performed better than based on G matrix, suggesting that traits with medium and high heritability are more suitable for the assessment of genetic connectedness compared to traits with low heritability. Our findings indicated that high-density SNP markers have advantages over pedigree analysis for the measurement of genetic connectedness, and CR is a robust and reliable method to assess genetic connectedness. Further, CR is easily calculated and less affected by heritability of trait. PEVD is good supplement to quantify the prediction errors of estimated breeding values under the specific genetic connectedness. In comparison, G matrix can reflect genetic connectedness better than its extensions Gs and G0.5 matrix.

Spinal muscular atrophy (SMA) is a common childhood neuromuscular disease inherited in an autosomal recessive pattern. The majority of SMA patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene. As a special SMA carrier, the (2+0) genotype ofSMN1 poses a great challenge for carrier screening and family genetic counseling. A previous study showed that polymorphisms of g.27134 T>G and g.27706_27707delAT had a predictive effect on (2+0) carriers in the Ashkenazi Jewish population. To further explore whether these two polymorphisms are specific to the Chinese population, the present study recruited 44 family members and 204 controls with knownSMN1copy number. These 44 family members were from nine unrelated SMA families withSMN1 homozygous deletion, and one of the proband parents was suspected to be a (2+0) carrier. Multiplex ligation-dependent probe amplification (MLPA) and short tandem repeat (STR) linkage analyses were used to determine the (2+0) genotype and polymorphism screening. Finally, by analyzing theSMN copies and haplotype from three generations of family members and two generations of multi-child families, ten individuals in nine families were confirmed as (2+0) carriers. Moreover, only one individual with three copies ofSMN1 carried the two polymorphisms of g.27134 T>G and g.27706_27707delAT. Therefore, we provided precise genetic counseling for these SMA families after confirming the (2+0) carriers. The association between the polymorphisms of g.27134T>G and g.27706_27707delAT and Chinese (2+0) carriers might be weak. Hence, it is necessary to find specific polymorphisms in the Chinese population to improve the detection rate of (2+0) carriers.

Trisomy 18 syndrome is one of the most common autosomal aneuploidy disorders. Little is known about the genetic regulation leading to the clinical phenotypes associated with the occurrence and development of trisomy 18 syndrome disorders (e.g., mental retardation, cardiac and renal abnormalities). To explore the regulatory factors that influence the phenotypes of the disease, this study used single-cell ATAC sequencing to analyze transcription factors in the accessibility chromatin regions of the single-nucleus cells of the cord blood from 18-trisomy syndrome and control subjects. A single-cell library constructed by capturing 11,611 cells identified seven major immune cell populations, and the results of cell number statistics suggested the presence of abnormalities in the immune system of 18-trisomy syndrome patients. Fourteen transcription factors (P<0.05, |FC|>1.2) were identified by analyzed accessibility chromatin regions. The relative expression levels of four of these transcription factors (TEAD1, TEAD2, TEAD4, Twist2) were confirmed using real-time quantitative fluorescence PCR. In conjunction with information from the literature, this study suggests that these four transcription factors may be associated with abnormalities in cardiac and skeletal development in patients with the 18-trisomy syndrome, thereby providing candidate molecules for mechanistic studies on the occurrence and development of the 18-trisomy syndrome phenotypes.

Potassium channels, which are the most diverse group of the ion channel family, play an important role in the repolarization of cardiomyocytes. Recent studies showed that potassium channels, such as KCNQ and HERG/eag, play an important role in regulating adult heart function through shaping the action potential and maintaining the rhythm of cardiac contraction. The potassium channel protein Shaker is the first voltage-gated potassium channel found in Drosophila to maintain the electrical excitability of neurons and muscle cells, but its role in adult cardiac function is still unclear. In this study, Drosophila was used as a model to study the role of Shaker channel in the maintenance of cardiac function under stress and aging. The incidence of heart failure was observed in shaker mutant after external electrical pacing, which simulates cardiac stress. Additionally, The cardiac-specific driver hand4.2 Gal4 was used to specifically knock down the expression of the potassium channel shaker in Drosophila. The cardiac parameter was analyzed at 1, 3, 5 weeks of age on cardiac specific knockdown of shaker using Drosophila adult cardiac physiological assay. The results showed that the mutation of shaker gene seriously affect the cardiac function under stress, demonstrated by significant increase in heart failure rate under electrical stimulation. In addition, cardiac specific knockdown of shaker increased the incidence of arrhythmias in Drosophila at the age of 5 weeks. Cardiac-specific knockdown of shaker reduces life span. Therefore, the results of this study suggest a vital role of the potassium channel shaker in maintaining normal cardiac function during aging.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs (19-25 nucleotides) that negatively regulate gene expression at the post transcriptional level by binding to complementary target sequences in the target mRNA. miRNAs play an important role in a wide range of biological processes, including organ development. Recent studies have shown that some miRNAs are highly expressed in the kidney and are closely related to kidney development and diseases, suggesting that miRNAs are important regulators in kidney physiology and pathology. This review will focus on the research progress of miRNA in kidney development, and discuss the role of miRNAs in the occurrence and development of renal dysplasia, which will provide a reference for the diagnosis and research of diseases related to kidney development.

Knowledge of the origin of eukaryotes is key to broadening our understanding of the eukaryotic genome and the relationship among internal structures within a eukaryotic cell. Since the discovery of archaea in 1977 and the proposal of three-domain tree of life by the American microbiologist Carl Woese, the intimate relationship in evolution between eukaryotes and archaea has been demonstrated by considerable experiments and analyses. From the beginning of the 21st century, with the development of phylogenetic methods and the discovery of new archaeal phyla more related to eukaryotes, increasing evidence has shown that Eukarya and Archaea should be merged into one domain, leading to a two-domain tree of life. Nowadays, the Asgard superphylum discovered via metagenomic analysis is regarded as the closest prokaryotes to eukaryotes. Nevertheless, several key questions are still under debate, such as what the ancestors of the eukaryotes were and when mitochondria emerged. Here, we review the current research progress regarding the changes of the tree of life and the detailed eukaryotic evolutionary mechanism. We show that the recent findings have greatly improved our knowledge on the origin of eukaryotes, which will pave the way for future studies.