Science China Life Sciences最新文献

Aquaculture represents the fastest-growing global food production sector, as it has become an essential component of the global food supply. China has the world's largest aquaculture industry in terms of production volume. However, the sustainable development of fish culture is hindered by several concerns, including germplasm degradation and disease outbreaks. The practice of genomic breeding, which relies heavily on genome information and genotypephenotype relationships, has significant potential for increasing the efficiency of aquaculture production. In 2014, the completion of the genome sequencing and annotation of the Chinese tongue sole signified the beginning of the fish genomics era in China. Since then, domestic researchers have made dramatic progress in functional genomic studies. To date, the genomes of more than 60 species of fish in China have been assembled and annotated. Based on these reference genomes, evolutionary, comparative, and functional genomic studies have revolutionized our understanding of a wide range of biologically and economically important traits of fishes, including growth and development, sex determination, disease resistance, metamorphosis, and pigmentation. Furthermore, genomic tools and breeding techniques such as SNP arrays, genomic selection, and genome editing have greatly accelerated genetic improvement through the incorporation of functional genomic information into breeding activities. This review aims to summarize the current status, advances, and perspectives of the genome resources, genomic study of important traits, and genomic breeding techniques of fish in China. The review will provide aquaculture researchers, fish breeders, and farmers with updated information concerning fish genomic research and breeding technology. The summary will help to promote the genetic improvement of production traits and thus will support the sustainable development of fish aquaculture.

The advent of CRISPR-Cas has revolutionized precise gene editing. While pioneering CRISPR nucleases like Cas9 and Cas12 generate targeted DNA double-strand breaks (DSB) for knockout or homology-directed repair, next generation CRISPR technologies enable gene editing without DNA DSB. Base editors directly convert bases, prime editors make diverse alterations, and dead Cas-regulator fusions allow nuanced control of gene expression, avoiding potentially risks like translocations. Meanwhile, the discovery of diminutive Cas12 orthologs and Obligate Mobile Element-Guided Activity (OMEGA) nucleases has overcome cargo limitations of adeno-associated viral vectors, expanding prospects for in vivo therapeutic delivery. Here, we review the ever-evolving landscape of cutting-edge gene editing tools, focusing on miniature Cas12 orthologs and OMEGA effectors amenable to single AAV packaging. We also summarize CRISPR therapies delivered using AAV vectors, discuss challenges such as efficiency and specificity, and look to the future of this transformative field of in vivo gene editing enabled by AAV vectors delivery.

Extrachromosomal DNA (ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity, oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments, but its diagnostic methods remain unmet. Extracellular matrix protein 1 (ECM1) has previously been reported to be a key factor in the induction and progression of liver fibrosis. However, little is known about the use of ECM1 as a biomarker to evaluate fibrosis. In a CCl₄-induced mouse model of liver fibrosis, the present study demonstrated that ECM1 decreased with gradually increasing fibrosis. Using biopsy as a reference, the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis, but there were no significant changes between fibrosis stage 2 and stage 0-1. To improve the performance of ECM1, age, platelet count, and ECM1 concentration were combined to calculate an EPA (ECM1-platelet-age) score (ranging from 0 to 10). The areas under the receiver operating characteristic curve of the EPA scores for the detection of F⩾2, F⩾3, and F4 were 0.6801, 0.7377, and 0.8083, respectively, which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio, APRI score, or FIB-4 score. In HBV patients following antiviral treatment, the dynamics of the EPA score depended on the status of liver fibrosis development. The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00% and 71.43%, respectively, while that of the LSM, another useful method for monitoring hepatic fibrosis changes during treatment, was only 52.00% and 7.14%, respectively. Compared with healthy controls, there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection, MAFLD, ALD, PBC, and DILI. These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury, and further examinations or medical care are needed. In conclusion, the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis. Additionally, ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.

Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment, yet their origins and underlying mechanisms remain uncertain. Here, we conduct a detailed investigation of sex differences in human pre-gastrulation embryos. The lower methylation and incomplete inactivation of the X chromosome in females, as well as the sex-specific cell-cell communication patterns, contribute to sex-differential transcription. Male trophectoderm is more inclined toward syncytiotrophoblast differentiation and exhibits a stronger hormone secretion capacity, while female trophectoderm tends to retain cytotrophoblast program with stronger mitochondrial function as well as higher vasculogenesis and immunotolerance signals. Male primitive endoderm initiates the anterior visceral endoderm transcriptional program earlier than females. The cell cycle activities of the epiblast and primitive endoderm are higher in males compared to females, while the situation is opposite in the trophectoderm. In conclusion, our study provides in-depth insights into the sex differences in human pre-gastrulation embryos and contributes to unraveling the origins of the sex differences in human fetal development.