Science China Life Sciences最新文献

Tripterygium wilfordii and T. hypoglaucum, which belong to family Celastraceae, are perennial vine shrubs with medicinal uses in treating rheumatoid arthritis, cancer, and male contraception. Among the bioactive ingredients, the macrocyclic dihydroagarofuran sesquiterpene alkaloids (DASAs), also serving as chemotaxonomic markers of Celastraceae, are well-known for cytotoxicity and insecticidal properties. Despite intensive phytochemical investigations over the last half-century, the DASAs biosynthetic pathway remains unsolved. Here, we mined multi-omics data of Tripterygium species and identified 14 sesquiterpene synthase genes. Detailed characterization revealed that a group of enzymes (TwTPS5, TwTPS16, ThTPS5) catalyzed the key step committed to the biosynthesis of DASAs in Tripterygium, as evidenced by CRISPR/Cas9 knockout of TwTPS5 in T. wilfordii. Our biochemical assay showed that these enzymes converted FPP to gamma-selinene. Homologues in other Celastraceae species (EaTPS3, CaTPS5, and CaTPS6) also produced gamma-selinene, suggesting functional conservation in this DASAs-producing lineage. Notably, knocking out TwTPS5 resulted in a reduction of DASAs and enhanced accumulation of pharmaceutically valuable compounds, generating a safer and innovative medicinal plant resource for future applications.

Coordination between different organelles and metabolic cues is crucial for resistance to pathogen invasion. As the core of maintaining cellular metabolism and homeostasis, mitochondria and lysosomes cooperate in the immune responses and elimination of intracellular pathogens. Previous research has focused on the function of one or the other in isolation, ignoring their pervasive interplay. In this review, we discuss the intricate mechanism of mitochondria-lysosome crosstalk and point out the role of AMP-activated protein kinase (AMPK)-transcription factor EB (TFEB) axis in microbial infections. The crosstalk between mitochondria and lysosomes affects cellular key processes, such as autophagy and programmed death, which play an important role in microbial infections.

Lipopolysaccharide (LPS)-induced endotoxemia is a key pathogenic factor in metabolic diseases. Probiotics reduce LPS levels and alleviate related disorders, but the underlying mechanism remains unclear. Here, we demonstrated that Christensenella tenuis alleviated endotoxemia and metabolic disorders in Diet-Induced Obese (DIO) mice by inhibiting the LPS-TLR4 signaling pathway and modulating downstream metabolism. Omics analysis revealed increased levels of gut free bile acids (BAs) after C. tenuis treatment, while in vitro experiments confirmed that C. tenuis hydrolyzed conjugated BAs into free BAs via bile salt hydrolase (BSH) activity. Further molecular dynamics simulations showed that free BAs formed non-membrane-permeable complexes with LPS, preventing the transmembrane translocation of intestinal LPS. Experimental evidence from isothermal titration calorimetry confirmed that free bile acids bound directly with LPS in an enthalpy-driven manner, which is consistent with in silico simulations and validates specific molecular interactions. Oral administration of free BAs also reduced plasma LPS levels in DIO mice. These findings uncover a novel mechanism by which BSH-positive gut microbes and probiotics benefit host metabolism and lay the groundwork for gut-targeted biotherapies for endotoxemia and metabolic diseases.

Maize (Zea mays L.) is not only an important cereal crop, but also a model plant species for genetic, cytologic, genomic, and molecular studies. Maize possesses tremendous phenotypic and genetic diversity. During the past few decades, researchers have made significant advances in multiple areas, including the genomic compositions and variations of maize and its ancestors, the genetic and genomic bases of maize domestication and evolution, the genetic architecture of various agronomic traits (yield, quality, biotic and abiotic stress responses, nutrient use efficiency, fertility and heterosis), and the development of novel molecular breeding technologies. In this review, we summarize these research achievements and provide a perspective for future maize research and breeding.

Understanding the adaptation of organisms to extreme environments is a fascinating topic in biology. Ciliated eukaryotes (ciliates) that inhabit high-salinity environments exhibit remarkable diversity. We revealed various structural and molecular adaptations through a comprehensive investigation of Schmidingerothrix, a ciliate tolerant to salinity levels of up to 25%. One key finding was the presence of a unique microtubule cytoskeleton under the pellicle of Schmidingerothrix, which significantly contributed to its high-salt adaptation. Our results highlight the essential role of coexisting halophilic bacteria in supporting the thriving of ciliates in culture. Contrary to previous studies, our findings indicated an inability to synthesize glycine betaine and ectoine in Schmidingerothrix. However, Schmidingerothrix appears to have expanded its repertoire of phagocytosis-related genes, suggesting a robust mechanism for the uptake and accumulation of compatible solutes via phagocytosis of halophilic bacteria. We expanded our investigation to other high-salt ciliates from different clades and discovered that microtubule cell-shape-supporting cytoskeletons and the phagocytic acquisition of compatible solutes were common strategies for high-salt adaptation. These findings significantly enhance our understanding of how ciliates adapt to high-salt environments and provide valuable insights into the high diversity of heterotrophic protists.

Paramecium, a group of ciliates with a long evolutionary history, plays essential roles in freshwater ecosystems and has been model for genetic, cellular, and evolutionary studies for over a century. Despite the valuable contributions of genomic resources such as ParameciumDB, genomic data are still mostly limited to species in and near the P. aurelia group. This study addresses this gap by HiFi sequencing, assembling, and annotating the macronuclear genomes of five rare Paramecium species: P. calkinsi, P. duboscqui, P. nephridiatum, P. putrinum, and P. woodruffi. These genomes enable a comprehensive exploration of genomic diversity, genome evolution, and phylogenomic relationships within the genus Paramecium. The genome sizes range from 47.78 to 113.16 Mb, reflecting unexpected variation in genomic content, and genic features differ from those of other reported Paramecium genomes, such as larger intron sizes and higher GC content. Nonetheless, the de novo assemblies indicate that macronuclear genomes of all Paramecium are highly streamlined, with ~77% being protein-coding gene regions. Based on gene-duplication depths, synonymous mutations in paralogs, and phylogenomic relationships, we discovered that the five species experienced at least three whole-genome duplication (WGD) events, independent of those previously found in the P. aurelia complex. Using all available WGD data for Paramecium, we further explore the paralog dynamics after WGD events by modeling. This study contributed to a more comprehensive and deeper understanding of genome architecture and evolution in Paramecium.