摘要: Hearing is one of the most vital sensory functions in human beings and a crucial means of perceiving and acquiring information from the natural environment. The advancement of human society is closely linked to the development of language, with hearing serving as the foundation for verbal communication. As individuals age, the deterioration of the auditory system becomes a significant factor contributing to sensory impairments in the elderly. In addition to hearing loss, the aging of the auditory system is also associated with cognitive decline and psychosocial disorders, which severely impact the quality of life for older adults. Currently, there are no effective treatments or interventions available for addressing the aging of the auditory system. Therefore, identifying biomarkers of the auditory system aging is of great significance. The Aging Biomarker Consortium of China has conducted a comprehensive evaluation of aging biomarkers in the auditory system, focusing on three dimensions: morphological, functional, and humoral biomarkers. This initiative aims to establish a foundation for assessing the degree of aging in the auditory system and to promote the management of auditory health in an aging society, ultimately enhancing the auditory health of the elderly population both in China and globally.

摘要: Oxidative stress diminishes the functionality of hematopoietic stem cells (HSCs) as age advances, with heightened reactive oxygen species (ROS) levels exacerbating DNA damage, cellular senescence, and hematopoietic impairment. DDO1002, a potent inhibitor of the NRF2-KEAP1 pathway, modulates the expression of antioxidant genes. Yet, the extent to which it mitigates hematopoietic decline post-total body irradiation (TBI) or in the context of aging remains to be elucidated. Our study has elucidated the role of DDO1002 in modulating NRF2 activity, which, in turn, activates the NRF2-driven antioxidant response element (ARE) signaling cascade. This activation can diminish intracellular levels of ROS, thereby attenuating cellular senescence. In addition, DDO1002 has been demonstrated to ameliorate DNA damage and avert HSC apoptosis, underscoring its potential to mitigate hematopoietic injury precipitated by TBI. Competitive transplantation assay revealed that the administration of DDO1002 can improve the reconstitution and self-renewal capacity of HSCs in aged mice. Single-cell sequencing analysis elucidated that DDO1002 treatment attenuated intracellular inflammatory signaling pathways and mitigated ROS pathway in aged HSCs, suggesting its potential to restore the viability of these cells. Consequently, DDO1002 effectively activated the NRF2-ARE pathway, delaying cellular senescence and ameliorating impaired hematopoiesis, thereby demonstrating its potential as a therapeutic agent for age-related hematopoietic disorders.

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摘要: The heterogeneity of ovarian mesenchymal/stromal cells has just been revealed in both mice and humans. However, it remains unclear about the cellular development trace and the intercellular communication network in the whole life of the ovary. In the study, we integrated ours and published single-cell RNA sequencing data from E11.5 (embryonic day 11.5) until M12 (12-month-old) ovaries to show the dynamics of somatic cells along the developmental timeline. The intercellular crosstalk among somatic cell types was depicted with collagen signaling pathway as the most outgoing signals from stromal cells. We identified mesenchymal progenitor cells (CD24⁺) as the origin of stromal cells. Although their numbers decreased significantly in adults, the cells served as the major signal sender until ovarian senescence. Moreover, the ovarian injury could activate these stem cells and induce stroma remodeling in the aged ovary. Thus, mesenchymal progenitor cells may represent a new strategy to delay ovarian aging in the future.

摘要: Proper chromosome alignment at the spindle equator is a prerequisite for accurate chromosome segregation during cell division. However, the chromosome movement trajectories prior to alignment remain elusive. Here, we established a 4D imaging analysis framework to visualize chromosome dynamics and develop a deep-learning model for chromosome movement trajectory classification. Our data reveal that chromosomes follow at least three distinct movement trajectories (retracing, congressing, and quasi-static) to arrive at the equator. We further revealed the distinct roles of multiple kinesin superfamily proteins (KIFs) in coordinating and maintaining the chromosome movement trajectories. In summary, we have presented an efficient and unbiased approach to studying chromosome dynamics during cell division, thereby uncovering a variety of chromosome movement trajectories that precede alignment.

摘要: The skeletal muscle is an important organ for movement and metabolism in human body, and its physiological aging underlies the occurrence of muscle atrophy and sarcopenia. China has the largest aging population in the world and is facing a grand challenge with how to prevent and treat skeletal muscle aging-related diseases. To address this difficult problem, the Aging Biomarker Consortium (ABC) of China has reached an expert consensus on biomarkers of skeletal muscle aging by synthesizing literatures and insights from scientists and clinicians. This consensus attempts to provide a comprehensive assessment of biomarkers associated with skeletal muscle aging, and proposes a systematic framework to classify them into three dimensions: functional, structural, and humoral. Within each dimension, the experts recommend clinically relevant biomarkers for skeletal muscle aging. This consensus aims to lay the foundation for future research on skeletal muscle aging, facilitating precise prediction, diagnosis, and treatment of skeletal muscle aging and sarcopenia. It is anticipated to make significant contributions to healthy aging of skeletal muscle in the elderly population in China and around the world as well.

摘要: The ovary plays a crucial role in the reproductive system of female mammals by producing mature oocytes through folliculogenesis. Non-human model organisms are extensively utilized in research on human ovarian biology, thus necessitating the investigation of conservation and divergence in molecular mechanisms across species. In this study, we employed integrative single-cell analysis of transcriptome and chromatin accessibility to identify the evolutionary conservation and divergence patterns of ovaries among humans, monkeys, mice, rats, and rabbits. Our analyses revealed that theca cells exhibited the most significant changes during evolution based on scRNA-seq and scATAC-seq datasets. Furthermore, we discovered common cis-regulatory architectures in theca cells across species by conducting joint analyses of scRNA-seq and scATAC-seq datasets. These findings have potential applications in non-human biomedical and genetic research to validate molecular mechanisms found in human organisms. Additionally, our investigation into non-coding genomic regions identified intergenic highly transcribed regions (igHTRs) that may contribute to the evolution of species-specific phenotypic traits. Overall, our study provides valuable insights into understanding the molecular characteristics of adult ovaries while offering new perspectives for studying human ovarian physiology and diseases.

摘要: Recurrent implantation failure (RIF) is a leading impediment to assisted reproductive technology, yet the underlying pathogenesis of RIF remains elusive. Recent studies have sought to uncover novel biomarkers and etiological factors of RIF by profiling transcriptomes of endometrial samples. Nonetheless, the inherent heterogeneity among published studies and a scarcity of experimental validations hinder the identification of robust markers of RIF. Hence, we integrated six publicly accessible datasets with 209 samples, including microarray profiles of endometrial samples in the secretory phase. After removing batch effects, we identified 175 differentially expressed genes. Gene set enrichment analysis identified dysregulation of immunological pathways in RIF. We also observed altered immune infiltration and pro-inflammatory cytokines in RIF. Protein-protein interaction network analysis identified ten hub genes, representing two co-expression modules significantly related to RIF. Knockdown of ENTPD3, one of the hub genes, promoted the epithelial-mesenchymal transition process and resulted in elevated levels of pro-inflammatory cytokines. Collectively, our study reveals abnormal gene expressions involving the regulation of epithelial-mesenchymal transition and immune status in RIF, providing valuable insights into its pathogenesis.

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