Science China Life Sciences最新文献

Phytophthora pathogens secrete numerous apoplastic effectors to manipulate host immunity. Herein, we identified a polysaccharide lyase 1 protein, PsPL1, which acts as an essential virulence factor of P. sojae infection in soybean. However, the overexpression of PsPL1 in P. sojae reduced infection and triggered enhanced immune responses in soybean. PsPL1 exhibited pectin lyase activity and degraded plant pectin to generate pectin oligosaccharides (POSs) with a polymerization degree of 3-14, exhibiting different levels of acetylation and methylation modifications. PsPL1 and the degraded pectin products triggered immune responses in soybean and different Solanaceous plants. The PsPL1-triggered immune responses required RSPL1, a membrane-localized leucine-rich repeat receptor-like protein, which is essential for Phytophthora resistance. Conversely, the PsPL1-degraded product-triggered immune responses depended on the membrane-localized lysin motif receptor-like kinase CERK1. This study reveals that the pectin lyase exhibits a dual immunogenic role during P. sojae infection, which activates plant resistance through different immune receptors and provides novel insights into the function of pectin lyase in host-pathogen interactions.

Selenium (Se) is an essential trace element of the utmost importance to human health. Its deficiency induces various disorders. Se species can be absorbed by organisms and metabolized to hydrogen selenide for the biosynthesis of selenoproteins, selenonucleic acids, or selenosugars. Se in mammals mainly acts as selenoproteins to exert their biological functions. The brain ranks highest in the specific hierarchy of organs to maintain the level of Se and the expression of selenoproteins under the circumstances of Se deficiency. Dyshomeostasis of Se and dysregulation of selenoproteins result in encephalopathy such as Alzheimer's disease, Parkinson's disease, depression, amyotrophic lateral sclerosis, and multiple sclerosis. This review provides a summary and discussion of Se metabolism, selenoprotein function, and their roles in modulating brain diseases based on the most currently published literature. It focuses on how Se is utilized and transported to the brain, how selenoproteins are biosynthesized and function physiologically in the brain, and how selenoproteins are involved in neurodegenerative diseases. At the end of this review, the perspectives and problems are outlined regarding Se and selenoproteins in the regulation of encephalopathy.

Epstein-Barr virus (EBV), the first human oncovirus discovered in 1964, has become a focal point in virology, immunology, and oncology because of its unique biological characteristics and significant role in human diseases. As we commemorate the 60th anniversary of EBV's discovery, it is an opportune moment to reflect on the major advancements in our understanding of this complex virus. In this review, we highlight key milestones in EBV research, including its virion structure and life cycle, interactions with the host immune system, association with EBV-associated diseases, and targeted intervention strategies.

SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.

The growing variety of RNA classes, such as mRNAs, lncRNAs, and circRNAs, plays pivotal roles in both developmental processes and various pathophysiological conditions. Nonetheless, our comprehension of RNA functions in live organisms remains limited due to the absence of durable and effective strategies for directly influencing RNA levels. In this study, we combined the CRISPR-RfxCas13d system with sperm-like stem cell-mediated semi-cloning techniques, which enabled the suppressed expression of different RNA species. This approach was employed to interfere with the expression of three types of RNA molecules: Sfmbt2 mRNA, Fendrr lncRNA, and circMan1a2(2,3,4,5,6). The results confirmed the critical roles of these RNAs in embryonic development, as their loss led to observable phenotypes, including embryonic lethality, delayed embryonic development, and embryo resorption. In summary, our methodology offers a potent toolkit for silencing specific RNA targets in living organisms without introducing genetic alterations.

CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins. While type I CRISPR systems in Class I may offer greater specificity and versatility, they are not well-developed for genome editing. Here, we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris (Dvu) for efficient and precise genome editing in mammalian cells and animals. We optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA strategy. These edited pig cells can serve as donors for generating transgenic cloned piglets. The Dvu type I-C editor also enabled precise large fragment replacements with homology-directed repair. Additionally, we adapted the Dvu-Cascade effector for cytosine and adenine base editing, developing Dvu-CBE and Dvu-ABE systems. These systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand breaks. Off-target analysis confirmed the high specificity of the Dvu type I-C editor. Our findings demonstrate the Dvu type I-C editor's potential for diverse mammalian genome editing applications, including deletions, fragment replacement, and base editing, with high efficiency and specificity for biomedicine and agriculture.