农学最新文献

[This corrects the article DOI: 10.1093/hr/uhad221.].

[This corrects the article DOI: 10.1093/hr/uhag140.].

Beginning approximately 4,000 years ago, southwest-Asian-originating domesticated crops and livestock began appearing in Gansu, a key crossroads in northwestern China, yet the population dynamics underlying these historically transformative events and the associated social practices in the region have not been fully explored. Despite the adoption of western domesticates, genome sequences of 149 individuals from the large Mogou cemetery and ten other sites in Gansu, dating between 4,700 and 3,000 years ago, revealed migrations within East Asian regions but no detectable evidence of genetic influence from western Eurasia, suggesting that early agricultural dispersals may have followed a model distinct from that documented in Europe and Central Asia. The Mogou cemetery represents a continuous community that interacted with surrounding regions but does not exhibit clear matrilocal or patrilocal patterns. We found no strong evidence that co-buried individuals represented biological relatives. Non-local ancestry appears to be linked to lower status burial practices. This study for the first time uncovers the histories of population migration, admixture and dispersal in Gansu from the late Neolithic to Bronze Age, and precisely reconstructs the social structure of the large Mogou cemetery in Gansu. It provides critical genetic evidence for understanding ancient human migration and dispersal as well as early social organization patterns in China.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but overdose causes severe acute liver injury. TMEM121 is an evolutionarily conserved transmembrane protein with high expression in liver tissue, yet its role in liver injury remains unknown. To investigate the function and molecular mechanism of the TMEM121 gene in APAP-induced injury in hepatoma carcinoma cells, we comprehensively employed three analytical approaches: bioinformatics prediction, cellular functional assays, and detection of key molecules in the pyroptosis pathway. Firstly, molecular docking analysis revealed that TMEM121 protein can directly bind to APAP. Analysis of the GSE104601 dataset and cellular experiments confirmed that APAP negatively regulates TMEM121 gene expression. Upon APAP stimulation, TMEM121 overexpression increased the sensitivity of Huh7 cells to APAP and reversed the promoting effects of TMEM121 on cell proliferation and migration observed under unstimulated conditions. Mechanistically, Western blotting and ELISA were used to assess key components of the pyroptosis pathway. The results demonstrated that, upon APAP stimulation, TMEM121 overexpression upregulated the expression of NLRP3 and caspase-1, promoted the cleavage of GSDMD to generate the active fragment GSDMD-N, and significantly increased the release of the inflammatory cytokines IL-1β and IL-18, thereby exacerbating pyroptosis. Furthermore, the lactate dehydrogenase release assay and transmission electron microscopy observation confirmed that TMEM121 overexpression aggravated APAP-induced cell membrane damage, leading to characteristic morphological features of pyroptosis, including membrane ballooning, rupture, and leakage of cellular contents. In summary, this study reveals that TMEM121 gene acts as a critical regulator of APAP-induced injury in Huh7 cells by activating the NLRP3/caspase-1/GSDMD signaling pathway and aggravating APAP-induced pyroptosis, providing novel mechanistic insights and potential therapeutic targets for APAP-induced hepatotoxicity.

Plumage color is one of the key phenotypic traits for breed identification in poultry, and deciphering its genetic basis is of great significance for the conservation and sustainable utilization of germplasm resources. In this study, we performed whole-genome resequencing (WGR) on 127 Guangdong Black pigeons and 12 Tarim pigeons, and integrated existing resequencing data from four other pigeon breeds (40 individuals in total). Principal component analysis, population structure analysis, and phylogenetic tree construction revealed that Guangdong Black pigeons have a unique genetic background and are clearly differentiated from white- and gray-feathered pigeon populations. We further conducted a genome-wide association study (GWAS), and after filtering and screening, identified a total of 1,598 single-nucleotide polymorphisms (SNPs) and 97 insertions/deletions (InDels). These loci were predominantly clustered in the endothelin receptor type B2 (EDNRB2) gene on chromosome 4 and in its flanking regions. From this region, we selected three highly significant SNPs and two InDels for Sanger sequencing validation. The results showed that all tested loci in white-feathered pigeons were wild-type, whereas in Guangdong Black pigeons they were either homozygous mutant or heterozygous, indicating that the genotypes at these variant loci are highly consistent with the black plumage phenotype. Our results provide reliable candidate markers for elucidating the molecular mechanism underlying plumage color formation in Guangdong Black pigeons and for implementing molecular marker-assisted breeding.

Spatiotemporal manipulation of gene expression is essential for dissecting gene function, elucidating developmental processes, and uncovering complex physiological mechanisms. As a model organism, Caenorhabditis elegans has played an important role in basic biology research and provides an ideal experimental system for achieving such precise control. With the development of single-copy transgenesis, CRISPR/Cas9-mediated genome editing, and conditional recombination and inducible systems, the genetic toolkits for spatiotemporal regulation of gene expression, and even at the single-cell-resolution, have been greatly expanded in C. elegans. In this review, we systematically summarize the major strategies for spatiotemporal regulation of gene expression in C. elegans, with a focus on tissue-specific RNA interference, conditional protein degradation systems, inducible transcriptional regulation systems, and recently developed approaches such as Ribo-on/Ribo-off. These methods are compared in terms of regulatory levels, technical advantages, limitations, and suitable applications. Together, these tools cover multiple layers of regulation, ranging from transcriptional and post-transcriptional control to protein-level manipulation, and provide powerful approaches for developmental biology, aging, inter-tissue signaling, and disease models, while also establishing a methodological foundation for dissecting cell-autonomous and non-cell-autonomous regulatory mechanisms in complex biological processes.

Duchenne muscular dystrophy (DMD) is the most common lethal neuromuscular genetic disorder in children. It is caused by mutations in the DMD gene that abolish the expression of dystrophin, a protein essential for maintaining sarcolemmal integrity during muscle contraction. Its loss renders muscle fibers susceptible to contraction-induced injury, leading to progressive muscle degeneration and, ultimately, fatal cardiac and respiratory failure. In this review, we summarize the diagnostic framework, molecular pathogenesis, and current therapeutic strategies of DMD, with particular emphasis on the recent advances in gene therapy-namely the mechanisms, clinical evidence, and technical challenges of exon skipping, gene replacement, and genome editing. Drawing on the latest findings, we further outline the major challenges and future directions of the field, aiming to provide a comprehensive reference for both basic research and clinical translation.

Medical genetics serves as a bridge between basic medical science and clinical courses. With its complex curriculum and abstract concepts, traditional lecture-based teaching often leads to difficulties in comprehension, diminishes students' interest in learning, and results in poor teaching outcomes. Incorporating typical case studies into instruction can make genetic theories more tangible, enhance students' intuitive understanding, facilitate their grasp of abstract concepts, and boost their interest in learning. Hereditary spastic paraplegia (HSP) is a group of hereditary neurological disorders characterized by progressive spastic paraplegia of both lower limbs. As a monogenic disorder, HSP exhibits high genetic heterogeneity. To date, more than 80 distinct disease-causing genes have been identified, encompassing various inheritance patterns such as autosomal dominant, autosomal recessive, and X-linked recessive inheritance. HSP has been included in China's first batch of rare disease listings, creating a need for genetic counseling. Prenatal diagnosis and differential diagnosis typically require integration with genetic testing. Case-based teaching focused on HSP can comprehensively cover the core concepts of medical genetics and help students develop a complete clinical genetic reasoning process from clinical phenotype to family analysis, genetic diagnosis, and risk assessment. Based on this educational philosophy, members in our teaching team explored teaching materials focusing on the genetic characteristics of HSP, including disease genes, genetic effect of mutation, pathogenesis, inheritance patterns, genetic diagnosis, and clinical treatment to construct a comprehensive, integrated case-based teaching framework and incorporated it throughout the teaching practice of medical genetics. Teachers implemented this instructional design in their medical genetics courses, transforming abstract theoretical instruction into accessible case-based teaching, which stimulated students' interest in learning and enhanced their ability to understand theories related to genetic diseases. This teaching reform facilitated the effective integration of genetic knowledge with clinical applications, fostered the development of clinical reasoning and research literacy among medical students, and provided an innovative method for medical genetics teaching.

Chromosome-scale three-dimensional interaction patterns within the nucleus represent a critical layer of higher-order genome organization. However, systematic comparative analyses of chromosome-scale interchromosomal interaction patterns across diverse cell types remain limited. In this study, we analyzed high-quality Hi-C datasets from 12 human cell types in the 4D Nucleome database, including pluripotent cells, hematopoietic lineage cells, tissue-specific cells, and cancer cells. To reduce scale bias in interchromosomal interaction analysis, we applied and validated a computational strategy based on chromosome length normalization. We further performed aggregation analysis at the cytogenetic G-banding level to quantitatively characterize chromosome spatial organization at the macroscopic scale. Our results showed that chromosome-scale organization in human cells follows a pattern of "conserved backbone with local modifications". A core spatial backbone composed of small chromosomes, including Chr16, Chr17, Chr19, and Chr20, was highly conserved across all examined cell types, whereas large chromosomes such as Chr2, Chr3, and Chr4 consistently ranked lower in interaction frequency. These findings support the large-scale stability of the chromosome territory model. Lineage analysis further showed that during hematopoietic differentiation, the modularity index of chromosome interaction networks increased significantly with functional specialization from 0.0417 to 0.0554, with P<0.0001 by Mann-Whitney U test, whereas tissue-specific cells maintained a stable structural state. In cancer cells, although the core backbone was preserved, abnormal interchromosomal interaction hotspots associated with structural variation were observed, such as Chr12-Chr21 in K562 and Chr8-Chr16 in HCT116. Overall, we systematically delineated chromosome-scale interaction patterns across distinct cellular lineages, providing new insights into the spatial organization principles of chromosomes in the nucleus and a reference framework for future studies linking three-dimensional genome architecture with structural genomic variation.

Topologically associating domains (TADs) are fundamental three-dimensional structural units of mammalian genomes and play critical roles in regulating genome organization and gene expression. However, the extreme sparsity of single-cell high-throughput chromosome conformation capture (single-cell Hi-C) data substantially degrades the features of TAD-like domains, posing significant challenges for their accurate identification. In this study, we proposed RecTAD, a single-cell TAD-like domain identification method based on Hi-C contact matrix reconstruction. Specifically, RecTAD reconstructed single-cell Hi-C contact matrices by integrating graph embedding with spectral propagation, thereby enhancing the underlying community information. Subsequently, TAD-like domains were identified from the reconstructed contact matrices using multi-scale Haar features. Extensive experimental results on downsampled bulk Hi-C data, simulated single-cell Hi-C data, and experimental single-cell Hi-C datasets demonstrate that RecTAD achieves superior identification accuracy and exhibits strong biological relevance. These results indicate that RecTAD provides an effective technical approach for analyzing three-dimensional genome architecture and investigating its regulatory mechanism at the single-cell level. The source code of RecTAD is publicly available at: https://github.com/doubletigerzju/ RecTAD.