Science China Life Sciences最新文献

Gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) present significant health challenges in China, often diagnosed at advanced stages with poor prognoses. However, effective biomarkers for early detection remain elusive. This study aimed to integrate methylome and transcriptome data to identify DNA methylation markers for the early detection of GCA and ESCC. In the discovery stage, we conducted Infinium MethylationEPIC array analysis on 36 paired GCA and non-tumor adjacent tissues (NAT), identifying differentially methylated CpG sites (DMCs) between GCA/ESCC and NAT through combined analyses of in-house and publicly available data. In the validation stage, targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT samples from 50 GCA and 50 ESCC patients. In the application stage, an independent set of 438 samples, including GCA, ESCC, high- and low-grade dysplasia (HGD/LGD), and normal controls, was tested for selected DMCs using pyrosequencing. Our analysis validated three GCA-specific, two ESCC-specific, and one tumor-shared DMCs, exhibiting significant hypermethylation and decreased expression of target genes in tumor samples compared with NAT. Leveraging these DMCs, we developed a GCA-specific 4-marker panel (cg27284428, cg11798358, cg07880787, and cg00585116) with an area under the receiver operating characteristic curve (AUC) of 0.917, effectively distinguishing between cardia HGD/GCA patients and cardia LGD/normal controls. Similarly, an ESCC-specific 3-marker panel (cg14633892, cg04415798, and cg00585116) achieved an AUC of 0.865 in distinguishing esophageal HGD/ESCC cases. Furthermore, integrating cg00585116, age, and alcohol consumption yielded a tumor-shared logistic model with good discrimination for two cancer/HGD (AUC, 0.767; 95% confidence interval, 0.720-0.813). The mean AUC of the model after 5-fold cross-validation was 0.764. In summary, our study identifies novel DNA methylation markers capable of accurately distinguishing GCA/ESCC and HGD from LGD and normal controls. These findings offer promising prospects for targeted DNA methylation assays in future minimally invasive cancer screening methods.

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.

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic.

Ruminant livestock provide a rich source of products, such as meat, milk, and wool, and play a critical role in global food security and nutrition. Over the past few decades, genomic studies of ruminant livestock have provided valuable insights into their domestication and the genetic basis of economically important traits, facilitating the breeding of elite varieties. In this review, we summarize the main advancements for domestic ruminants in reference genome assemblies, population genomics, and the identification of functional genes or variants for phenotypic traits. These traits include meat and carcass quality, reproduction, milk production, feed efficiency, wool and cashmere yield, horn development, tail type, coat color, environmental adaptation, and disease resistance. Functional genomic research is entering a new era with the advancements of graphical pangenomics and telomere-to-telomere (T2T) gap-free genome assembly. These advancements promise to improve our understanding of domestication and the molecular mechanisms underlying economically important traits in ruminant livestock. Finally, we provide new perspectives and future directions for genomic research on ruminant genomes. We suggest how ever-increasing multiomics datasets will facilitate future studies and molecular breeding in livestock, including the potential to uncover novel genetic mechanisms underlying phenotypic traits, to enable more accurate genomic prediction models, and to accelerate genetic improvement programs.

Chemotherapy is regarded as a widely used and effective treatment strategy for lung cancer, although most conventional chemotherapeutics cause severe toxic side-effects due to their indiscriminate attacks on both cancerous and normal cells. Although nucleic acid nanomaterials are emerging as a promising drug delivery strategy, their clinical applications are limited by rapid degradation by nucleases and difficulties in targeting cancer cells. In this study, we have developed a Rhein-loaded aptamer-based DNA nanotube (DNT-S6@Rhein) for the targeted and efficient therapy of non-small cell lung cancer. Through the palindrome segments, two specified oligonucleotides were hybridized and folded into the well-defined nanotubes (DNT-S6), with the S6 aptamer distributed outside. The obtained nanotubes exhibited excellent serum stability and targeting ability towards A549 cells due to the firm structure and decoration of the S6 aptamer. Rhein, as an antitumor drug and DNA intercalator, can be effectively inserted into the DNT-S6. The drug-loaded nanotubes rapidly disassembled in intracellular environment and then the released Rhein was found to activate cellular apoptotic process and significantly suppress proliferation, migration and invasion of A549 cells. Moreover, DNT-S6@Rhein could efficiently accumulate in tumor regions, offering compelling therapeutic efficacy and biocompatibility under both in vitro and in vivo settings. These findings of this study provide a promising strategy for mitigating the inevitable systemic side-effects of chemotherapy and expand the potential application of DNA nanostructure on targeted drug delivery.

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.