Science China Life Sciences最新文献

Circular RNAs (circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However, the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA, circTP63-N, generated through the splicing of exons 2-4 of the TP63 gene in nasopharyngeal carcinoma (NPC). circTP63-N was found to be downregulated in clinical samples of NPC. Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells. Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein, leading to the recruitment of LATS/YAP1 proteins. This, in turn, induced phosphorylation and ubiquitination-dependent degradation of YAP1, resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes, including INHBA, MMP3, and CCNE2. Our findings highlight the identification of circTP63-N, a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC. These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

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.

Chicken gut microbiota plays an important role in maintaining their physiological health. However, the cultivability of chicken gut microbiota is not well understood, limiting the exploration of certain key gut bacteria in regulating intestinal health and nutritional metabolism. This study aimed to examine the cultivability of chicken cecal microbiota and to provide guidance for future chicken gut microbiota cultivation. A total of 58 different culture conditions were applied to culture broiler cecal microbiota, and the culture-dependent (CD; pooled colonies form each plate) and culture-independent (CI; broiler cecal contents) samples were collected for 16S rRNA gene sequencing and microbial analysis. The CD methods detected higher microbial richness (3,636 vs 2,331 OTUs) than CI methods, and the recovery rates of bacterial OTUs and genera reached 43.6% and 68.9%, respectively. The genera of Bacteroides (19.9%), Alistipes (11.0%) and Barnesiella (10.7%) were highly abundant detected by CI methods, however, there occupied a small proportion (<1.0%) of total cultured microbiota in CD methods. We then developed reference figures and tables showing optimal cultivation conditions for different gut bacteria taxa. Moreover, 81 different lactic acid bacteria strains covering 5 genera were isolated, and 15 strains had less than 97.0% similarity to known bacteria in the national center for biotechnology information (NCBI) online database. Overall, this study provides preliminary guidance in culturing specific gut microbiota from chickens, which will contribute to future studies to characterize the biological functions of key microbes in chicken nutritional metabolism and health.

Cell fate changes play a crucial role in the processes of natural development, disease progression, and the efficacy of therapeutic interventions. The definition of the various types of cell fate changes, including cell expansion, differentiation, transdifferentiation, dedifferentiation, reprogramming, and state transitions, represents a complex and evolving field of research known as cell lineage tracing. This review will systematically introduce the research history and progress in this field, which can be broadly divided into two parts: prospective tracing and retrospective tracing. The initial section encompasses an array of methodologies pertaining to isotope labeling, transient fluorescent tracers, non-fluorescent transient tracers, non-fluorescent genetic markers, fluorescent protein, genetic marker delivery, genetic recombination, exogenous DNA barcodes, CRISPR-Cas9 mediated DNA barcodes, and base editor-mediated DNA barcodes. The second part of the review covers genetic mosaicism, genomic DNA alteration, TCR/BCR, DNA methylation, and mitochondrial DNA mutation. In the final section, we will address the principal challenges and prospective avenues of enquiry in the field of cell lineage tracing, with a particular focus on the sequencing techniques and mathematical models pertinent to single-cell genetic lineage tracing, and the value of pursuing a more comprehensive investigation at both the spatial and temporal levels in the study of cell lineage tracing.

Cell metabolism is an indispensable biochemical process that provides the basic energy and materials necessary for normal cell function. Accumulating evidence implicates abnormal metabolism of T cells as playing a critical role in the pathogenesis of rheumatoid arthritis (RA). The deacetylase SIRT3 has been shown to directly regulate energy metabolism in nonimmune cells. However, the role of SIRT3 in T cells and whether it participates in RA process remain unclear. In this study, we demonstrated that T-cell glycolysis was inhibited after SIRT3 deficiency. Compared to wild-type mice, SIRT3 knockout mice exhibited more severe arthritis, cartilage erosion, and inflammation after immunization with antigen-induced arthritis (AIA). It is interesting to note that SIRT3 deficiency reduced the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a regulatory and rate-limiting enzyme in glycolysis. Overexpression of PFKFB3 was shown to restore the impaired ATP production caused by SIRT3 deficiency in T cells, and protects T cells from apoptosis. In summary, SIRT3 plays an important role in the regulation of T-cell metabolism in the pathogenesis of RA. SIRT3 deficiency decreases glycolysis, reduces ATP production, induces apoptosis in CD4⁺ T cells, and further promotes AIA in mice.

The numbers of new cancer cases and deaths in China were the largest in the world, causing a huge social and economic burden. We attempt to use more intuitive indicators to measure the probabilities of being diagnosed of or dying from cancer in China and compare these probabilities with those in Japan and the United States (US). We obtained the cancer data from GLOBOCAN 2022 for China, Japan, and the US and the all-cause mortality and population data from the United Nations. The lifetime risks of developing and dying from cancer were estimated with adjusted actual life expectancy, multiple primaries, and death-competing risks from causes other than cancers. Approximately 27.61% of Chinese people developed cancer and 1 in 5 persons were likely to die from cancer. The highest-risk cancer among men and women was lung cancer in China, but in the US and Japan, prostate cancer among men and breast cancer among women posed the highest risk. Lung cancer presented the highest likelihood of death, but women in Japan had the highest likelihood of dying from colorectal cancer. China had a lower lifetime risk of developing cancer compared with Japan and the US, but a higher probability of dying from cancer than the US. Although the probability of developing cancer was not as high as that in Japan and the US, China was still faced with enormous pressure due to its huge population and contradictory cancer patterns. Estimating lifetime risks can provide essential information to formulate appropriate cancer prevention and control plans.

As an alternative model for studying the dynamic process of early mammalian embryonic development, much progress has been made in using mouse embryonic stem cells (mESCs) to generate embryo-like structures, especially by modifying the starting cells. A previous study has demonstrated that totipotent blastomere-like cells (TBLCs) can be obtained by continuous treatment of mESCs with a low-dose splicing inhibitor, Pladienolide B (PlaB). However, these totipotent mESCs have limited proliferative capacity. Here, we report that short-term high-dose PlaB treatment can also induce mESCs to acquire totipotency. This treatment equips this novel type of stem cells with the ability to self-organize into blastoids and recapitulate key preimplantation developmental processes. Therefore, the stem cells are termed transient totipotent blastomere-like stem cells (tTBLCs). Transcriptome analysis showed that tTBLC blastoids bore similarities to mouse E3.5 blastocysts, E4.5 blastocysts, and TBLC blastoids. Additionally, we found that tTBLC blastoids could develop beyond the implantation stage, forming egg-cylinder-like structures both in vitro and in vivo. In summary, our research provides an alternative rapid and convenient method to generate the starting cells capable of developing into blastoids, which have immense application in various fields, not only in the basic study of early mouse embryogenesis but also in high-throughput drug screening.