Single‐cell dynamics of chromatin activity during cell lineage differentiation in Caenorhabditis elegans embryos

Elucidating the chromatin dynamics that orchestrate embryogenesis is a fundamental question in developmental biology. Here, we exploit position effects on expression as an indicator of chromatin activity and infer the chromatin activity landscape in every lineaged cell during Caenorhabditis elegans early embryogenesis. Systems‐level analyses reveal that chromatin activity distinguishes cellular states and correlates with fate patterning in the early embryos. As cell lineage unfolds, chromatin activity diversifies in a lineage‐dependent manner, with switch‐like changes accompanying anterior–posterior fate asymmetry and characteristic landscapes being established in different cell lineages. Upon tissue differentiation, cellular chromatin from distinct lineages converges according to tissue types but retains stable memories of lineage history, contributing to intra‐tissue cell heterogeneity. However, the chromatin landscapes of cells organized in a left–right symmetric pattern are predetermined to be analogous in early progenitors so as to pre‐set equivalent states. Finally, genome‐wide analysis identifies many regions exhibiting concordant chromatin activity changes that mediate the co‐regulation of functionally related genes during differentiation. Collectively, our study reveals the developmental and genomic dynamics of chromatin activity at the single‐cell level.     

Secondary Structural Transformation of Bovine Lactoferricin Affects Its Antibacterial Activity

Probiotics and Antimicrobial Proteins - Lactoferricin (Lfcin) is a potent antibacterial peptide derived from lactoferrin by pepsin hydrolysis. It was hypothesized that structural transformation of...     

A new Illumina MiSeq high-throughput sequencing-based method for evaluating the composition of the Bacteroides community in the intestine using the rpsD gene sequence

Bacteroides is a bacterial genus that is known to closely interact with the host. The potential role of this genus is associated with its ecological status and distribution in the intestine. However, the current 16S V3–V4 region sequencing method can only detect the abundance of this genus, revealing a need for a novel sequencing method that can elucidate the composition of Bacteroides in the human gut microbiota. In this study, a core gene, rpsD, was selected as a template for the design of a Bacteroides-specific primer set. We used this primer set to develop a novel assay based on the Illumina MiSeq sequencing platform that enabled an accurate assessment of the Bacteroides compositions in complex samples. Known amounts of genomic DNA from 10 Bacteroides species were mixed with a complex sample and used to evaluate the performance and detection limit of our assay. The results were highly consistent with those of direct sequencing with a low Bacteroides DNA detection threshold (0.01 ng), supporting the reliability of our assay. In addition, the assay could detect all the known Bacteroides species within the faecal sample. In summary, we provide a sensitive and specific approach to determining the Bacteroides species in complex samples.     

Using vaginal discharge score (VDS) grading system to evaluate the effect of clinical endometritis on reproductive performance of dairy cows in China

Clinical endometritis (CE) is a major cause in affecting the reproductive performance of dairy cows. The objectives of this study were to ascertain the prevalence of CE and to evaluate the effect of CE on reproductive performance in dairy cows using vaginal discharge score (VDS) grading system. 803 dairy cows were examined by vaginoscope with 4-point VDS at 26 ± 3 days in milk (DIM) and classified into six groups: non-endometritis with VDS 0 (control; CON), endometritis with VDS 1 (MEM), non-treated endometritis with VDS 2 (NTME), treated endometritis with VDS 2 (TME), non-treated endometritis with VDS 3 (NTPE), and treated endometritis with VDS 3 (TPE). Cows in TME and TPE groups were treated with 200 mL of 50% dextrose solution by intrauterine infusion. The prevalence of CE was 33% at 26 ± 3 DIM. Binary logistic regression analysis revealed cows in MEM, NTME and NTPE groups had a less likelihood of first artificial insemination (AI) pregnancy than those in CON group (P < 0.05). Kaplan-Meier survival curves for days open were statistically different (P = 0.004). In Cox regression model, cows in NTME and NTPE groups had a reduced pregnancy rate than those in CON group (P < 0.05). The hazard of pregnancy in NTME group was lower than that in TME group (P = 0.044). Similarly, it was lower for the hazard of pregnancy in NTPE group than in TPE group (P = 0.048). Cows in MEM, NTME, and NTPE groups required more services per pregnancy than those in CON group (P < 0.05). In conclusion, CE examined by the VDS grading system impaired reproductive performance, and mild endometritis with VDS 1 should be treated in the early postpartum period to ameliorate fertility in dairy herds.     

Middle Jurassic radiolarians from Jinlang,Zedong, southern Xizang (Tibet), China

Moderately to well-preserved radiolarians have been extracted from nine greyish green and purplish-red bedded cherts in the mud-matrix mélange of the eastern Yarlung-Zangbo Suture Zone (YZSZ) at Jinlang Section, Zedong, southern Xizang (Tibet). Forty-two species belonging to 27 genera, including Middle Jurassic characteristic species such as Laxtorum (?) jurassicum Isozaki and Matsuda, Laxtorum (?) hichisoense Isozaki and Matsuda, Stichocapsa japonica Yao, Stichocapsa robusta Matsuoka, Parahsuum (?) magnum Takemura, Sella chrafatensis (El Kadiri), and Unuma typicus Ichikawa and Yao are recognized and three assemblages, Laxtorum (?) jurassicum Assemblage (Aalenian), Quarticella ovalis Assemblage (late Bajocian), and Stichocapsa robusta Assemblage (middle Bathonian) are established in ascending order. These assemblages can be well correlated to the Middle Jurassic Unitary Association (UA) Zones (Baumgartner et al., 1995) in west Tethys and coeval biozones in Japan and provide reliable age information for the Middle Jurassic stratigraphic correlation of the pelagic sediments along the YZSZ.     

LncRNA-HOTAIR promotes endothelial cell pyroptosis by regulating the miR-22/NLRP3 axis in hyperuricaemia

Long non-coding RNA (lncRNA) plays an important role in the renal inflammatory response caused by hyperuricaemia. However, the underlying molecular mechanisms through which lncRNA is involved in endothelial injury induced by hyperuricaemia remain unclear. In this study, we investigated the regulatory role of lncRNA-HOTAIR in high concentration of uric acid (HUA)–induced renal injury. We established hyperuricaemia mouse model and an in vitro uric acid (UA)–induced human umbilical vein endothelial cell (HUVEC) injury model. In HUA-treated HUVECs and hyperuricaemia mice, we observed increased HOTAIR and decreased miR-22 expression. The expression of pyroptosis-associated protein (NLRP3, Caspase-1, GSDMD-N, GSDMD-FL) was increased. The release of LDH, IL-1β and IL-18 in cell supernatants and the sera of model mice was also increased. The proliferation of HUVECs stimulated by HUA was significantly inhibited, and the number of TUNEL-positive cells in hyperuricaemia mouse kidney was increased. Bioinformatics analysis and luciferase reporter and RIP assays confirmed that HOTAIR promoted NLRP3 inflammasome activation by competitively binding miR-22. In gain- or loss-of-function experiments, we found that HOTAIR and NLRP3 overexpression or miR-22 knock down activated the NLRP3 inflammasome and promoted pyroptosis in HUA-treated HUVECs, while NLRP3 and HOTAIR knockdown or a miR-22 mimic exerted the opposite effects. Furthermore, in vivo experiments validated that HOTAIR knockdown alleviated renal inflammation in hyperuricaemia mice. In conclusion, we demonstrated that in hyperuricaemia, lncRNA-HOTAIR promotes endothelial cell pyroptosis by competitively binding miR-22 to regulate NLRP3 expression.     

Inhibition of cyclooxygenase-2 enhanced intestinal epithelial homeostasis via suppressing β-catenin signalling pathway in experimental liver fibrosis

The intestinal barrier dysfunction is crucial for the development of liver fibrosis but can be disturbed by intestinal chronic inflammation characterized with cyclooxygenase-2 (COX-2) expression. This study focused on the unknown mechanism by which COX-2 regulates intestinal epithelial homeostasis in liver fibrosis. The animal models of liver fibrosis induced with TAA were established in rats and in intestinal epithelial–specific COX-2 knockout mice. The impacts of COX-2 on intestinal epithelial homeostasis via suppressing β-catenin signalling pathway were verified pharmacologically and genetically in vivo. A similar assumption was tested in Ls174T cells with goblet cell phenotype in vitro. Firstly, disruption of intestinal epithelial homeostasis in cirrhotic rats was ameliorated by celecoxib, a selective COX-2 inhibitor. Then, β-catenin signalling pathway in cirrhotic rats was associated with the activation of COX-2. Furthermore, intestinal epithelial–specific COX-2 knockout could suppress β-catenin signalling pathway and restore the disruption of ileal epithelial homeostasis in cirrhotic mice. Moreover, the effect of COX-2/PGE2 was dependent on the β-catenin signalling pathway in Ls174T cells. Therefore, inhibition of COX-2 may enhance intestinal epithelial homeostasis via suppression of the β-catenin signalling pathway in liver fibrosis.     

Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan-cancer cohort

Tumour-derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell-free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan-cancer patients of Chinese and explored effects of CH on liquid biopsies in real-world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K-Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty-eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision-making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real-world.