Over the past two decades, numerous non-coding RNAs (ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses such as herpesviruses. As a representative oncogenic alphaherpesvirus, Marek's disease virus (MDV) causes an important immunosuppressive and rapid-onset neoplastic disease of poultry, namely Marek's disease (MD). Vaccinations can efficiently prevent the onset of MD lymphomas and other clinical disease, often heralded as the first successful example of vaccination-based control of cancer. MDV infection is also an excellent model for research into virally-induced tumorigenesis. Recently, great progress has been made in understanding the functions of ncRNAs in MD biology. Herein, we give a review of the discovery and identification of MDV-encoded viral miRNAs, focusing on the genomics, expression profiles, and emerging critical roles of MDV-1 miRNAs as oncogenic miRNAs (oncomiRs) or tumor suppressor genes involved in the induction of MD lymphomas. We also described the involvements of host cellular miRNAs, lincRNAs, and circRNAs participating in MDV life cycle, pathogenesis, and/or tumorigenesis. The prospects, strategies, and new techniques such as the CRISPR/Cas9-based gene editing applicable for further investigation into the ncRNA-mediated regulatory mechanisms in MDV pathogenesis/oncogenesis were also discussed, together with the possibilities of future studies on antiviral therapy and the development of new efficient MD vaccines.

Immunocytes, including the microglia, are crucial in the neurodegenerative process in old people. However, the understanding of regarding microglia heterogeneity and other involved immunocytes remains elusive. We analyzed 26,456 immunocytes from 12-and 26-month-old zebrafish brains at single-cell resolution. Microglia and T lymphocytes were detected in the brain at both time points. Two types of microglia were annotated, namely, ac+ microglia and xr+ microglia, which were clustered into subsets 1, 2, 3, 4, 5, and subsets 6, 7, 8, 9, respectively. Diversified microglia predominated the adult brains and cooperated with T cells to perform the functions of immune response and neuronal nutrition. We validated the specific microglia markers. The novel transgenic lines, Tg(lgals3bpb:eGFP) and Tg(apoc1:eGFP), were created, which faithfully labeled ac+ microglia and served as valuable labeling tools. However, the microglia population reduced while T cells of six subtypes intriguingly increased to serve as the primary immune cells in aged brains. Unlike in 12-month-old brains, T cells, together with microglia, exhibited a coordinated signature of inflammation in the 26-month-old brains. Our findings revealed the immunocytes atlas in aged zebrafish brains. It implied the involvement of microglia and T cells in the progression of neurodegeneration in aging.

Genome sequencing has revealed that actinomycetes possess the potential to produce many more secondary metabolites than previously thought. The existing challenge is to devise efficient methods to activate these silent biosynthetic gene clusters (BGCs). In Streptomyces ansochromogenes, disruption of wblA, a pleiotropic regulatory gene, activated the expression of cryptic tylosin analogues and abolished nikkomycin production simultaneously. Overexpressing pathway-specific regulatory genes tylR1 and tylR2 can also trigger the biosynthesis of silent tylosin analogues, in which TylR1 exerted its function via enhancing tylR2 expression. Bacterial one-hybrid system experiments unveiled that WblA directly inhibits the transcription of tylR1 and tylR2 to result in the silence of tylosin analogues BGC. Furthermore, WblA can activate the nikkomycin production through up-regulating the transcription of pleiotropic regulatory gene adpA. More interestingly, AdpA can activate sanG (an activator gene in nikkomycin BGC) but repress wblA. Our studies provide a valuable insight into the complex functions of pleiotropic regulators.

Programmed DNA double-strand break (DSB) formation is a crucial step in meiotic recombination, yet techniques for high-efficiency and precise mapping of the 3' ends of DSBs are still in their infancy. Here, we report a novel technique, named DNA End tailing and sequencing (DEtail-seq), which can directly and ultra-efficiently characterize the 3' ends of meiotic DSBs with near single-nucleotide resolution in a variety of species, including yeast, mouse, and human. We find that the 3' ends of meiotic DSBs are stable without significant resection in budding yeast. Meiotic DSBs are strongly enriched in de novo H3K4me3 peaks in the mouse genome at leptotene stage. We also profile meiotic DSBs in human and find DSB hotspots are enriched near the common fragile sites during human meiosis, especially at CCCTC-binding factor (CTCF)-associated enhancers. Therefore, DEtail-seq provides a powerful method to detect DSB ends in various species, and our results provide new insights into the distribution and regulation of meiotic DSB hotspots.

Carbon-nitrogen coupling is a fundamental principle in ecosystem ecology. However, how the coupling responds to global change has not yet been examined. Through a comprehensive and systematic literature review, we assessed how the dynamics of carbon processes change with increasing nitrogen input and how nitrogen processes change with increasing carbon input under global change. Our review shows that nitrogen input to the ecosystem mostly stimulates plant primary productivity but inconsistently decreases microbial activities or increases soil carbon sequestration, with nitrogen leaching and nitrogenous gas emission rapidly increasing. Nitrogen fixation increases and nitrogen leaching decreases to improve soil nitrogen availability and support plant growth and ecosystem carbon sequestration under elevated CO2 and temperature or along ecosystem succession. We conclude that soil nitrogen cycle processes continually adjust to change in response to either overload under nitrogen addition or deficiency under CO2 enrichment and ecosystem succession to couple with carbon cycling. Indeed, processes of both carbon and nitrogen cycles continually adjust under global change, leading to dynamic coupling in carbon and nitrogen cycles. The dynamic coupling framework reconciles previous debates on the "uncoupling" or "decoupling" of ecosystem carbon and nitrogen cycles under global change. Ecosystem models failing to simulate these dynamic adjustments cannot simulate carbon-nitrogen coupling nor predict ecosystem carbon sequestration well.

The maintenance of proteostasis is essential for cellular and organism healthspan. How proteostasis collapse influences reproductive span remains largely unclear. In Caenorhabditis elegans, excess accumulation of vitellogenins, the major components in yolk proteins, is crucial for the development of the embryo and occurs throughout the whole body during the aging process. Here, we show that vitellogenin accumulation leads to reproduction cessation. Excess vitellogenin is accumulated in the intestine and transported into the germline, impairing lysosomal activity in these tissues. The lysosomal function in the germline is required for reproductive span by maintaining oocyte quality. In contrast, autophagy and sperm depletion are not involved in vitellogenin accumulation-induced reproductive aging. Our findings provide insights into how proteome imbalance has an impact on reproductive aging and imply that improvement of lysosomal function is an effective approach for mid-life intervention for maintaining reproductive health in mammals.

Wild animals and plants have developed a variety of adaptive traits driven by adaptive evolution, an important strategy for species survival and persistence. Uncovering the molecular mechanisms of adaptive evolution is the key to understanding species diversification, phenotypic convergence, and inter-species interaction. As the genome sequences of more and more non-model organisms are becoming available, the focus of studies on molecular mechanisms of adaptive evolution has shifted from the candidate gene method to genetic mapping based on genome-wide scanning. In this study, we reviewed the latest research advances in wild animals and plants, focusing on adaptive traits, convergent evolution, and coevolution. Firstly, we focused on the adaptive evolution of morphological, behavioral, and physiological traits. Secondly, we reviewed the phenotypic convergences of life history traits and responding to environmental pressures, and the underlying molecular convergence mechanisms. Thirdly, we summarized the advances of coevolution, including the four main types: mutualism, parasitism, predation and competition. Overall, these latest advances greatly increase our understanding of the underlying molecular mechanisms for diverse adaptive traits and species interaction, demonstrating that the development of evolutionary biology has been greatly accelerated by multi-omics technologies. Finally, we highlighted the emerging trends and future prospects around the above three aspects of adaptive evolution.

High hydrostatic pressure, low temperature, and scarce food supply are the major factors that limit the survival of vertebrates in extreme deep-sea environments. Here, we constructed a high-quality genome of the deep-sea Muddy arrowtooth eel (MAE, Ilyophis brunneus, captured below a depth of 3,500 m) by using Illumina, PacBio, and Hi-C sequencing. We compare it against those of shallow-water eel and other outgroups to explore the genetic basis that underlies the adaptive evolution to deep-sea biomes. The MAE genome was estimated to be 1.47 Gb and assembled into 14 pseudo-chromosomes. Phylogenetic analyses indicated that MAE diverged from its closely related shallow-sea species, European eel, ∼111.9 Mya and experienced a rapid evolution. The genome evolutionary analyses primarily revealed the following: (i) under high hydrostatic pressure, the positively selected gene TUBGCP3 and the expanded family MLC1 may improve the cytoskeleton stability; ACOX1 may enhance the fluidity of cell membrane and maintain transport activity; the expansion of ABCC12 gene family may enhance the integrity of DNA; (ii) positively selected HARS likely maintain the transcription ability at low temperatures; and (iii) energy metabolism under a food-limited environment may be increased by expanded and positively selected genes in AMPK and mTOR signaling pathways.

Mammalian embryogenesis begins with a totipotent zygote. Blastocyst-like structures can be captured by aggregated cells with extended pluripotent properties in a three-dimensional (3D) culture system. However, the efficiency of generating blastoids is low, and it remains unclear whether other reported totipotent-like stem cells retain a similar capacity. In this study, we demonstrated that spliceosomal repression-induced totipotent blastomere-like cells (TBLCs) form blastocyst-like structures within around 80% of all microwells. In addition, we generated blastoids initiating from a single TBLC. TBLC-blastoids express specific markers of constituent cell lineages of a blastocyst and resemble blastocyst in cell-lineage allocation. Moreover, single-cell RNA sequencing revealed that TBLC-blastoids share a similar transcriptional profile to natural embryos, albeit composed of fewer primitive endoderm-like cells. Furthermore, TBLC-blastoids can develop beyond the implantation stage in vitro and induce decidualization in vivo. In summary, our findings provided an alternative cell type to efficiently generate blastoids for the study of early mouse embryogenesis.