A spatiotemporal atlas of cholestatic injury and repair in mice.

Cholestatic liver injuries, characterized by regional damage around the bile ductular region, lack curative therapies and cause considerable mortality. Here we generated a high-definition spatiotemporal atlas of gene expression during cholestatic injury and repair in mice by integrating spatial enhanced resolution omics sequencing and single-cell transcriptomics. Spatiotemporal analyses revealed a key role of cholangiocyte-driven signaling correlating with the periportal damage-repair response.

Cell atlas of CCl -induced progressive liver fibrosis reveals stage-specific responses.

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis, a major cause of morbidity and mortality worldwide. However, there are currently no effective anti-fibrotic therapies available, especially for late-stage patients, which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cell-specific responses in different fibrosis stages. To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes, we generated a single-nucleus transcriptomic atlas encompassing 49 919 nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride (CCl )-induced progressive liver fibrosis.

Immune response and homeostasis mechanism following administration of BBIBP-CorV SARS-CoV-2 inactivated vaccine.

The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16 monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8 T cells, along with increased activation of CD4 T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4 T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination.

Single-cell transcriptional diversity of neonatal umbilical cord blood immune cells reveals neonatal immune tolerance.

The characteristics of neonatal immune cells display intrinsic differences compared with adult immune cells. Therefore, a comprehensive analysis of key gene expression regulation is required to understand the response of the human fetal immune system to infections. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) to systematically profile umbilical cord blood (UCB) nucleated cells and peripheral blood mononuclear cells (PBMCs) to identify their composition and differentially expressed genes.

Systematic analyses reveal RNA editing events involved in skeletal muscle development of goat (Capra hircus).

RNA editing is a posttranscriptional molecular process involved with specific nucleic modification, which can enhance the diversity of gene products. Adenosine-to-inosine (A-to-I, I is read as guanosine by both splicing and translation machinery) is the main type of RNA editing in mammals, which manifested as AG (adenosine-to-guanosine) in sequence data. Here, we aimed to explore patterns of RNA editing using RNA sequencing data from skeletal muscle at four developmental stages (three fetal periods and one postnatal period) in goat.

Transcriptome Profiling of Placenta through Pregnancy Reveals Dysregulation of Bile Acids Transport and Detoxification Function.

Placenta performs the function of several adult organs for the fetus during intrauterine life. Because of the dramatic physiological and metabolic changes during pregnancy and the strong association between maternal metabolism and placental function, the possibility that variation in gene expression patterns during pregnancy might be linked to fetal health warrants investigation. Here, next-generation RNA sequencing was used to investigate the expression profile, including mRNAs and long non-coding RNAs (lncRNAs) of placentas on day 60 of gestation (G60), day 90 of gestation (G90), and on the farrowing day (L0) in pregnant swine.

Mammary Protein Synthesis upon Long-Term Nutritional Restriction Was Attenuated by Oxidative-Stress-Induced Inhibition of Vacuolar H-Adenosine Triphosphatase/Mechanistic Target of Rapamycin Complex 1 Signaling.

To determine how nutritional restriction compromised milk synthesis, sows were fed 100% (control) or 76% (restricted) of the recommended feed allowance from postpartum day (PD)-1 to PD-28. In comparison to the control, more body reserves loss, increased plasma triglyceride and high-density lipoprotein cholesterol levels, and decreased plasma methionine concentrations were observed in the restricted group at PD-21. The increased plasma malondialdehyde level, decreased plasma histidine and taurine concentrations, and decreased glutathione peroxidase activity were observed at PD-28 when backfat loss further increased in the restricted group.

Targeted metabolomics analysis of maternal-placental-fetal metabolism in pregnant swine reveals links in fetal bile acid homeostasis and sulfation capacity.

Cholestasis of pregnancy endangers fetal and neonatal survival, yet systematic knowledge of the cause and effect of disrupted bile acid (BA) homeostasis in pregnancy is limited. Here we show that gestation stage-associated BA dysregulation in swine correlated with fetal death resulting from compromised capacity for BA secretion and increased alternative systemic efflux. The balance of BA input and output in the developing uterus suggested little uptake and metabolism of maternal BA by the placenta-fetus unit, implying a protection role of placenta in preventing maternal BA transported into the fetus.

Mammary cell proliferation and catabolism of adipose tissues in nutrition-restricted lactating sows were associated with extracellular high glutamate levels.

Background: Persistent lactation, as the result of mammary cellular anabolism and secreting function, is dependent on substantial mobilization or catabolism of body reserves under nutritional deficiency. However, little is known about the biochemical mechanisms for nutrition-restricted lactating animals to simultaneously maintain the anabolism of mammary cells while catabolism of body reserves. In present study, lactating sows with restricted feed allowance (RFA) ( = 6), 24% feed restriction compared with the control (CON) group ( = 6), were used as the nutrition-restricted model.

mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources.

Mechanistic target of rapamycin complex1 (mTORC1) activation and protein synthesis varied with methionine sources; however, the related mechanisms are largely unknown. Porcine mammary epithelial cells (PMEC) and mammary tissue slices (MTS) were used to test whether methionine precursors differ in providing the available methionine and thus differ in mTORC1 signaling-associated protein synthesis. PMEC with methionine deprivation for 8 h and MTS from lactating sows were cultured for 24 and 2 h, respectively, with treatment media without methionine (negative control, NC) or supplemented with 0.

Rearing conditions affected responses of weaned pigs to organic acids showing a positive effect on digestibility, microflora and immunity.

Three experiments were conducted to assess the response of weaned pigs to organic acid SF3, which contains 34% calcium formate, 16% calcium lactate, 7% citric acid and 13% medium chain fatty acids. Dietary treatments had no effect on growth performance of piglets (21-day weaning) fed the commercial prestart diet for 1 week before receiving the experimental diets supplemented with SF3 at 0, 3 or 5 g/kg diet (Exp. 1), whereas diarrhea frequency averaged across a week was decreased by SF3 supplementation (5 g/kg diet) in piglets fed the experimental diets immediately after weaning (Exp.