Science China Life Sciences最新文献

CD8⁺ T cells are the primary killer cells that fight infections and malignantly transformed cells in vivo. In response to various stimuli, activated CD8⁺ T cells differentiate into effector and memory CD8⁺ T cells, which eliminate target cells and provide long-term protective immunity, respectively. Aberrant CD8⁺ T cell function induced by aging can lead to immune-related disorders. Both endogenous and exogenous stress affect the aging process of CD8⁺ T cells. CD8⁺ T cell aging results in cell senescence, characterized by disrupted cell proliferation, and impairs many other CD8⁺ T cell-related immune responses. It is now well-established that the aging of immune cells, including CD8⁺ T cells, exacerbates the body's inflammation and promotes cell senescence in distant tissues, thereby accelerating the onset and progression of age-related diseases. Therefore, clarifying the genetic characteristics, molecular mechanisms, and specific markers of aged CD8⁺ T cells is crucial for delivering precise and effective therapeutic interventions for age-related diseases, particularly those induced by CD8⁺ T cell aging.

Emerging evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in ferroptosis regulation, yet the detailed mechanisms remain largely elusive. In this study, we identify LINC00942, a ferroptosis-associated lncRNA, which localizes to mitochondria and coordinates ferroptosis and tumorigenesis by modulating mitochondrial function. Bioinformatic analysis establishes that LINC00942 is specifically overexpressed in hepatocellular carcinoma (HCC), and its high expression is closely associated with poor patient prognosis. Both in vitro and in vivo experiments demonstrate that LINC00942 promotes HCC cell proliferation, migration, and invasion. Furthermore, suppression of LINC00942 disrupts mitochondrial function, impairs energy metabolism, and increases mitochondrial lipid peroxidation and reactive oxygen species (ROS) levels, rendering HCC cells more susceptible to ferroptosis. Mechanistically, LINC00942 interacts with G-rich sequence factor 1 (GRSF1) and subsequently translocates to the mitochondria. Within mitochondria, LINC00942 facilitates the binding of GRSF1 to complex I mRNA, thereby enhancing the translation efficiency of complex I subunits. The resulting upregulation of complex I protein levels strengthens its enzymatic activity and promotes mitochondrial oxidative phosphorylation, while concurrently suppressing ferroptosis. In addition, DNA demethylation and CREB1 contribute to the transcriptional activation of LINC00942 in HCC. Notably, administration of GalNAc-conjugated siRNA targeting LINC00942 effectively suppresses tumor growth in orthotopic xenograft models. Collectively, these findings underscore the oncogenic function of LINC00942 through the modulation of mitochondrial bioenergetics and ferroptosis, highlighting it as a promising therapeutic target for HCC.

Ovarian aging poses significant challenges to female fertility and overall health. While whole-grain black rice diet (BRD) has emerged as a promising anti-aging intervention, its translational potential for ovarian health remains underexplored. This study systematically evaluated BRD's effects on ovarian functional decline through single-cell profiling and phenotypic validation. We demonstrated that BRD intervention effectively delays ovarian aging by preserving the ovarian reserve and maintaining hormonal balance, with granulosa cells (GCs) exhibiting the most pronounced responsiveness. Notably, BRD counteracts age-associated reductions in the GCs population and restores ovarian functional capacity. These findings highlight BRD's ability to rejuvenate the ovarian cellular landscape and stabilize aging-related tran-scriptional profiles. Our study provides actionable insights for developing BRD-based nutritional strategies to combat female reproductive aging, paving the way for clinically translatable dietary interventions and functional food innovations targeting the extension of women's healthspan.

As space exploration advances into the era of deep space exploration, humanity faces unprecedented challenges in maintaining astronaut health, not only during prolonged space travel but also in adapting to low-gravity environments, such as those on the Moon or Mars. Extended exposure to the space environment accelerates the physiological aging process, triggering changes that impact multiple systems. These effects highlight the urgent need for effective countermeasures. Exercise has been shown to mitigate the detrimental impacts of microgravity on cardiovascular and musculoskeletal systems, including reduced cardiac reserve, arterial stiffening, venous thrombosis, metabolic dysfunction, and frailty. In addition, exercise offers potential benefits in reducing aging-related declines in mental health and immune function during extended space missions. This review synthesizes evidence on physical exercise as a critical countermeasure, analyzing its role across the mission lifecycle: pre-flight conditioning, in-flight mitigation, and post-flight rehabilitation, as well as the underlying mechanisms involved. We also evaluate strategies for optimizing exercise regimens and key metrics for assessing astronaut health outcomes. Developing scientifically rigorous, individualized exercise protocols supported by emerging technologies such as artificial intelligence promises to enhance astronaut cardiovascular health, optimize mission performance, and minimize the risks associated with long-duration space travel and gravity variations.

Neurons in distinct spinal cord segments serve specific functions, raising questions about whether human spinal cord-derived neural stem cells (hscNSCs) retain segment-specific properties crucial for spinal cord injury (SCI) repair. We established a culture system amplifying hscNSCs from cervical, thoracic, and lumbar segments, revealing segment-specific transcriptional profiles and differentiation potentials. Notably, thoracic hscNSCs exhibited elevated hepatocyte growth factor (HGF) expression inherited from the pre-ganglionic column, enhancing their differentiation into motor neurons. Transplantation of thoracic hscNSCs into thoracic SCI rat models demonstrated superior graft survival, neural regeneration, and functional recovery compared with cervical or lumbar counterparts. Thoracic hscNSCs reduced inflammation, minimized glial scar formation, and significantly improved locomotor function post-SCI. Our findings underscore the importance of segment-specific properties of hscNSCs in optimizing SCI repair outcomes, paving the way for tailored therapeutic strategies in spinal cord regeneration.

The life cycle of flowering plants starts when a zygote is formed following a double fertilization event. To achieve fertilization, sperm cells are delivered to the female gametes within the embryo sac by the tip-growing pollen tube. The fast-growing pollen tube is characterized and regulated by abundant transport vesicles responsible for both exocytosis and endocytosis in the tip region. Visualization of these tip-vesicles has been challenging owing to their small size, high dynamics, and complexity. In this study, we illustrated the three-dimensional (3D) ultrastructure of tip-vesicles in growing pollen tubes of lily, tobacco, and Arabidopsis. Five major types of tip-vesicles, including secretory vesicles (SVs), electron-dense vesicles (DVs), clathrin-coated vesicles (CCVs), mini vesicles (MVs), and extracellular vesicles (EVs), can be distinguished using room-temperature electron tomography (RT-ET) based on their ultrastructural features. We also demonstrated the extensive distribution of tubular endoplasmic reticulum (ER) structures at the apex of growing pollen tubes and vesicles budding from the tip-localized ER. Cryo-ET further revealed the tip-localized tubular ER with budding coat protein complex II (COPII) vesicles. Our study thus offered a structural basis for a deeper comprehension of vesicular trafficking in the tip growth of the pollen tube, aiding future research on vesicle-mediated membrane trafficking in polarized cell growth.

Adenomyosis remains a challenging gynecological disorder to investigate due to the absence of in vitro models that accurately replicate endometrial tissue dynamics across the menstrual cycle. To address this gap, we established an endometrial assembloid model that faithfully mimics cycle-dependent endometrial responses and captures key cellular and molecular hallmarks of adenomyosis, including ectopic lesion- specific epithelial and stromal heterogeneity. Single-cell transcriptomics revealed that ectopic epithelial cells shift toward a luminal- dominant, glandular-deficient transcriptional profile during the secretory-like phase. This transition correlated with ectopic stromal reorganization-specifically, loss of BMP4⁺ stromal cells and an accumulation of CRYAB⁺IL15⁺ stromal cells-which impaired BMP-mediated stromal-epithelial signaling while enhancing WNT activation. Additionally, ectopic epithelial and stromal cells demonstrated increased immunity and angiogenesis activities. Our assembloid platform not only provides a physiologically relevant model for investigating adenomyosis pathogenesis but also implicates aberrant WNT signaling as a potential therapeutic target, offering new opportunities for mechanism-driven treatment strategies.