High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently. The high-order structures of both the paternal and maternal genomes in zygotes and two-cell embryos are obscure but are gradually re-established through development. The establishment of the TAD structure requires DNA replication but not zygotic genome activation. Furthermore, unmethylated CpGs are enriched in A compartment, and methylation levels are decreased to a greater extent in A compartment than in B compartment in embryos. In summary, the global reprogramming of chromatin architecture occurs during early mammalian development.

In this paper, we introduce the plurigenera, Kodaira dimensions and more generally Iitaka dimensions on compact almost complex manifolds. These are equal to the original notions when the almost complex structure is integrable. The definitions are based on the Hodge theory on almost complex manifolds. An alternative interpretation using pseudoholomorphic maps leads to fundamental geometric consequences.We show that the plurigenera and the Kodaira dimension as well as the irregularity are birational invariants in almost complex category, at least in dimension 4, where a birational morphism is defined to be a degree one pseudoholomorphic map. However, they are no longer deformation invariants, even in dimension 4 or under tameness assumption. For tamed almost complex 4-manifolds, our Kodaira dimension is bounded above by the symplectic Kodaira dimension.By studying pluricanonical maps, we are able to show the almost complex structures that achieve the top Kodaira dimension are integrable. On the other hand, the Kodaira dimension could take all the other possible integer values for non-integrable almost complex structures.When we apply our invariants to the standard almost complex structure on the six sphere S 6 , we show the Kodaira dimension is 0 and all the plurigenera are 1, which is different from the data of a hypothetical complex structure.In the appendix, we show the uniqueness of subvarieties in exceptional curve classes for irrational symplectic 4-manifolds, which was a question of the second author.

Docetaxel-based chemotherapy is a standard-of-care treatment for metastatic prostate cancer (PCa), and chemoresistance remains a major challenge in clinical practice. Recent studies have demonstrated that circular RNAs (circRNAs) play critical roles in the development and progression of PCa. However, the biological roles and potential functions of circRNAs in mediating docetaxel-resistant PCa have yet to be well elucidated. In this study, we analyzed the expression profiles of circRNAs in docetaxel-resistant and -sensitive PCa cells through RNA sequencing and found that expression of circARHGAP29 was significantly upregulated in docetaxel-resistant cell lines and clinical samples. Ectopic expression of circARHGAP29 triggered docetaxel resistance and aerobic glycolysis in PCa cells, which was reduced by silencing circARHGAP29. Moreover, eukaryotic initiation factor 4A3 (EIF4A3), which bound the back-spliced junction site and the downstream flanking sequence of circARHGAP29, induced cyclization and cytoplasmic export of circARHGAP29. circARHGAP29 increased the stability of lactate dehydrogenase A (LDHA) mRNA by strengthening its interaction with insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), leading to enhanced glycolytic metabolism. In addition, circARHGAP29 interacted with and stabilized c-Myc mRNA and protein, which further increased LDHA expression by facilitating its transcription. These findings reveal the crucial function of circARHGAP29 in PCa glycolysis by increasing and stabilizing LDHA mRNA, providing a promising therapeutic target in docetaxel-resistant PCa. SignificanceUpregulation of a novel circRNA, circARHGAP29, promotes docetaxel resistance and glycolytic metabolism, suggesting it could be a prognostic biomarker and therapeutic target in chemoresistant prostate cancer.Research.

No abstract

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expressions of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. Globally, BGs have been used as vaccine delivery systems and vaccine adjuvants. There is an increasing interest in the development of novel delivery systems that are based on BGs for biomedical applications. Due to intact reservation of bacterial cell membranes, BGs have an inherent immunogenicity, which enables targeted drug delivery and controlled release. As carrier vehicles, BGs protect drugs from interference by external factors. In recent years, there has been an increasing interest in BG-based delivery systems against tumors, inflammation, and infection, among others. Herein, we reviewed the preparation methods for BGs, interactions between BGs and the host, and further highlighted research progress in BG development.

Five triplicate groups containing 15 Jian carp (33.51 ± 1.91 g) were fed five isonitrogenous (30%) and isolipidic (8%) diets, with an increase in silkworm chrysalis oil (SCO) to replace soybean oil (SO) at 0 (SO), 25 (SCO25), 50 (SCO50), 75 (SCO75), or 100% (SCO100) levels for 59 d. Results showed that the SCO50 and SCO75 groups presented higher thermal growth coefficients than the SO and SCO100 groups and lower feed conversion ratios than the SCO100 group (P < 0.05). Moreover, the 50% SCO‐supplemented level decreased hepatopancreas lipid content and increased muscle crude protein content (P < 0.05). Meanwhile, α‐linolenic acid, n‐3 polyunsaturated fatty acid (PUFA) content, and n‐3/n‐6 PUFA ratio increased in the hepatopancreas, and intraperitoneal fat and muscle as the replacement of SO increased (P < 0.05). No significant differences of the serum biochemical indices and hepatopancreatic malondialdehyde content were found among groups (P > 0.05), but hepatopancreatic superoxide dismutase activities in the SCO25 and SCO50 groups were significantly higher than those in the other groups (P < 0.05). There was no significant difference in muscularis coat thickness, fold height, and fold width in the mid‐intestine (P>0.05). Overall, up to 50 or 75% replacement of SO by SCO in the diet of Jian carp could improve growth performance without affecting the health status of the fish.

Background Lung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation in enhancer and super-enhancer landscapes of LUAD patients remains largely unknown. To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we investigate the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explore the role of epigenetic alterations in LUAD progression. Results A high intertumoral epigenetic heterogeneity is observed across the LUAD H3K27ac profiles. We quantitatively model the intertumoral variability of H3K27ac levels at proximal gene promoters and distal enhancers and propose a new epigenetic classification of LUAD patients. Our classification defines two LUAD subgroups which are highly related to histological subtypes. Group II patients have significantly worse prognosis than group I, which is further confirmed in the public TCGA-LUAD cohort. Differential RNA-seq analysis between group I and group II groups reveals that those genes upregulated in group II group tend to promote cell proliferation and induce cell de-differentiation. We construct the gene co-expression networks and identify group-specific core regulators. Most of these core regulators are linked with group-specific regulatory elements, such as super-enhancers. We further show that CLU is regulated by 3 group I-specific core regulators and works as a novel tumor suppressor in LUAD. Conclusions Our study systematically characterizes the epigenetic alterations during LUAD progression and provides a new classification model that is helpful for predicting patient prognosis.

No abstract