DNA Methylation and Subgenome Dominance Reveal the Role of Lipid Metabolism in Jinhu Grouper Heterosis.

Heterosis of growth traits in economic fish has benefited the production of aquaculture for many years, yet its genetic and molecular basis has remained obscure. Nowadays, a new germplasm of hybrid Jinhu grouper (Epinephelus fuscoguttatus ♀ × E. tukula ♂), abbreviated as EFT, exhibiting paternal-biased growth heterosis, has provided an excellent model for investigating the potential regulatory mechanisms of heterosis. We integrated transcriptome and methylome to unravel the changes of gene expression, epigenetic modification, and subgenome dominance in EFT compared with maternal E. fuscoguttatus. Integration analyses showed that the heterotic hybrids showed lower genomic DNA methylation levels than the purebred parent, and the up-regulated genes were mostly DNA hypomethylation. Furthermore, allele-specific expression (ASE) detected paternal subgenome dominance-regulated paternal-biased heterosis, and paternal bias differentially expressed genes (DEGs) were wholly up-regulated in the muscle. Multi-omics results highlighted the role of lipid metabolism, particularly "Fatty acid synthesis", "EPA biosynthesis", and "Signaling lipids", in EFT heterosis formation. Coherently, our studies have proved that the eicosapentaenoic acid (EPA) of EFT was greater than that of maternal E. fuscoguttatus (8.46% vs. 7.46%). Finally, we constructed a potential regulatory network for control of the heterosis formation in EFT. Among them, fasn, pparg, dgat1, igf1, pomca, fgf8a, and fgfr4 were identified as key genes. Our results provide new and valuable clues for understanding paternal-biased growth heterosis in EFT, taking a significant step towards the molecular basis of heterosis.

Comparative Transcriptome Analysis of the Hypothalamic-Pituitary-Gonadal Axis of Jinhu Grouper (Epinephelus fuscoguttatus ♀ × Epinephelus tukula ♂) and Tiger Grouper (Epinephelus fuscoguttatus).

Jinhu groupers, the hybrid offspring of tiger groupers (Epinephelus fuscoguttatus) and potato groupers (Epinephelus tukula), have excellent heterosis in fast growth and strong stress resistance. However, compared with the maternal tiger grouper, Jinhu groupers show delayed gonadal development. To explore the interspecific difference in gonadal development, we compared the transcriptomes of brain, pituitary, and gonadal tissues between Jinhu groupers and tiger groupers at 24-months old. In total, 3034 differentially expressed genes (DEGs) were obtained. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that the osteoclast differentiation, oocyte meiosis, and ovarian steroidogenesis may be involved in the difference in gonadal development. Trend analysis showed that the DEGs were mainly related to signal transduction and cell growth and death. Additionally, differences in expression levels of nr4a1, pgr, dmrta2, tbx19, and cyp19a1 may be related to gonadal retardation in Jinhu groupers. A weighted gene co-expression network analysis revealed three modules (i.e., saddlebrown, paleturquoise, and greenyellow) that were significantly related to gonadal development in the brain, pituitary, and gonadal tissues, respectively, of Jinhu groupers and tiger groupers. Network diagrams of the target modules were constructed and the respective hub genes were determined (i.e., cdh6, col18a1, and hat1). This study provides additional insight into the molecular mechanism underlying ovarian stunting in grouper hybrids.

Effects of Long-Term Cryopreservation on the Transcriptomes of Giant Grouper Sperm.

The giant grouper fish (Epinephelus lanceolatus), one of the largest and rarest groupers, is a fast-growing economic fish. Grouper sperm is often used for cross-breeding with other fish and therefore sperm cryopreservation is important. However, freezing damage cannot be avoided. Herein, we performed a transcriptome analysis to compare fresh and frozen sperm of the giant grouper with frozen storage times of 0, 23, 49, and 61 months. In total, 1911 differentially expressed genes (DEGs), including 91 in El-0-vs-El-23 (40 upregulated and 51 downregulated), 251 in El-0-vs-El-49 (152 upregulated and 69 downregulated), and 1569 in El-0-vs-El-61 (984 upregulated and 585 downregulated), were obtained in the giant grouper sperm. DEGs were significantly increased at 61 months of cryopreservation (p < 0.05). GO and KEGG enrichment analyses of the DEGs revealed significant enrichment in the pilus assembly, metabolic process, MAPK signaling pathway, apoptosis, and P53 signaling pathway. Time-series expression profiling of the DEGs showed that consistently upregulated modules were also significantly enriched in signaling pathways associated with apoptosis. Four genes, scarb1, odf3, exoc8, and atp5f1d, were associated with mitochondria and flagella in a weighted correlation network analysis. These genes may play an important role in the response to sperm freezing. The experimental results show that long-term cryopreservation results in freezing damage to the giant grouper sperm. This study provides rich data for studies of the mechanism underlying frozen fish sperm damage as well as a technical reference and evaluation index for the long-term cryopreservation of fish sperm.

Natural killer cells at the forefront of cancer immunotherapy with immune potency, genetic engineering, and nanotechnology.

Natural killer (NK) cells are vital components of the human immune system, acting as innate lymphocytes and playing a crucial role in immune surveillance. Their unique ability to independently eliminate target cells without antigen contact or antibodies has sparked interest in immunological research. This review examines recent NK cell developments and applications, encompassing immune functions, interactions with target cells, genetic engineering techniques, pharmaceutical interventions, and implications in cancers. Insights into NK cell regulation emerge, with a focus on promising genetic engineering like CAR-engineered NK cells, enhancing specificity against tumors. Immune checkpoint inhibitors also enhance NK cells' potential in cancer therapy. Nanotechnology's emergence as a tool for targeted drug delivery to improve NK cell therapies is explored. In conclusion, NK cells are pivotal in immunity, holding exciting potential in cancer immunotherapy. Ongoing research promises novel therapeutic strategies, advancing immunotherapy and medical interventions.

Hepatic GRK2 is dispensable for glucose homeostasis and other key metabolic parameters in mice.

OBJECTIVE: G-protein-coupled receptor (GPCR) kinases (GRKs) abrogate GPCR signaling by promoting receptor desensitization and internalization. Accumulating evidence suggests that GRK2 represents an important regulator of GPCR-mediated effects on systemic glucose metabolism, obesity, and insulin resistance. Despite the key role of the liver in maintaining euglycemia, the potential metabolic relevance of hepatic GRK2 has yet to be examined. Thus, the goal of this study was to explore the potential role of hepatic GRK2 in maintaining glucose homeostasis and other key metabolic functions. METHODS: To address this question, we generated mice that showed a ∼90% reduction in GRK2 protein expression selectively in hepatocytes (Hep-GRK2-KO mice) and subjected these mice, together with their control littermates, to systematic metabolic phenotyping studies. RESULTS: We found that Hep-GRK2-KO mice maintained on regular chow did not differ significantly from their control littermates in glycemia, glucose tolerance, insulin sensitivity, in vivo gluconeogenesis, and glucagon-induced hyperglycemia. We obtained similar findings when we analyzed Hep-GRK2-KO mice and control littermates consuming an obesogenic high-fat diet. Likewise, plasma levels of insulin, glucagon, free fatty acids, and ketone bodies remained unaffected by the lack of hepatocyte GRK2. The same was true when we examined the expression levels of key genes regulating hepatic glucose and fatty acid metabolism. CONCLUSION: In summary, our data suggest that hepatocyte GRK2 is dispensable for systemic glucose homeostasis and other key metabolic functions in both lean and obese mice. This finding suggests that drug development efforts aimed at inhibiting GRK2 to improve impaired glucose homeostasis and insulin sensitivity need to focus on other metabolically important tissues.

Advancements and applications of single-cell multi-omics techniques in cancer research: Unveiling heterogeneity and paving the way for precision therapeutics.

Single-cell multi-omics technologies have revolutionized cancer research by allowing us to examine individual cells at a molecular level. Unlike traditional bulk omics approaches, which analyze populations of cells together, single-cell multi-omics enables us to uncover the heterogeneity within tumors and understand the unique molecular characteristics of different cell populations. By doing so, we can identify rare subpopulations of cells that are influential in tumor growth, metastasis, and resistance to therapy. Moreover, single-cell multi-omics analysis provides valuable insights into the immune response triggered by various therapeutic interventions, such as immune checkpoint blockade, chemotherapy, and cell therapy. It also helps us better understand the intricate tumor microenvironment and its impact on patient prognosis and response to treatment. This comprehensive review focuses on the recent advancements in single-cell multi-omics methodologies, with an emphasis on single-cell multi-omics technologies. It highlights the important role of these techniques in uncovering the complexity of tumorigenesis and its multiple applications in cancer research, as well as their equally great contributions in other areas such as immunology. Through single-cell multi-omics, we gain a deeper understanding of cancer biology and pave the way for more precise and effective therapeutic strategies. Apart from those above, this paper also aims to introduce the advancements in live cell imaging technology, the latest developments in protein detection techniques, and explore their seamless integration with single-cell multi-omics technology.

Copper-mediated novel cell death pathway in tumor cells and implications for innovative cancer therapies.

Previous investigations have unraveled an array of cellular demise modalities, encompassing apoptosis, necrosis, pyroptosis, iron death, and several others. These diverse pathways of cell death have been harnessed as therapeutic strategies for eradicating tumor cells. Recent scientific inquiries have unveiled a novel mode of cell death, namely copper death, which is contingent upon intracellular copper levels. Diverging from conventional cell death mechanisms, copper death exhibits a heightened reliance on mitochondrial respiration, specifically the tricarboxylic acid (TCA) cycle. Tumor cells exhibit distinctive metabolic profiles and an elevated copper content compared to their normal counterparts. The emergence of copper death presents a tantalizing prospect for targeted therapies in the realm of cancer treatment. Thus, the primary objective of this review is to introduce the proteins and intricate mechanisms underlying copper death, while comprehensively summarizing the extensive body of knowledge concerning its ramifications across diverse tumor types. The insights garnered from this comprehensive synthesis will serve as an invaluable reference for driving the development of tailor-made therapeutic interventions for tumors.

Nickel Foam Supported NiO@Ru Heterostructure Towards High-Efficiency Overall Water Splitting.

Electrocatalytic water splitting for hydrogen production from renewable energy requires the innovation of electrocatalysts with high activity and low cost. In this work, densely packed NiO@Ru nanosheets were fabricated on the surface of Ni foam through a two-step method of Ni(OH)2 growth followed by Ru deposition. Through pair distribution function analysis from selected-area electron diffraction and X-ray photoelectron spectroscopy, the interface structure feature is revealed as a thin layer of perovskite NiRuO3 sandwiched between NiO and Ru. The electrode exhibits high activity and durability for HER and OER, delivering a current density of 10 mA cm-2 at a voltage of 1.55 V for overall water splitting in 1 M KOH. The excellent performance can be attributed to the intimate interface contact of NiO and Ru in addition to low charge transfer resistance and super-hydrophilic surface structure, as verified by the electrochemical impedance spectroscopy and contact-angle measurement.