Science China Life Sciences最新文献

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.

The amh (anti-Müllerian hormone) gene, residing on the sex chromosomes, has been hypothesized to be a potential master sex gene in amphidiploid Carassius auratus (crucian carp/goldfish). However, its role in male determination or differentiation remains unclear. Here, we identified the heteromorphic X and Y chromosomes and confirmed the localization of amh on the sex chromosome by fluorescence in situ hybridization in amphidiploid C. auratus. The transcriptional expressions of X-linked and Y-linked amh alleles showed no significant difference during the period of sex determination and differentiation. The mutation of either the X-linked or Y-linked amh allele did not result in sex reversal, while the disruption of both amh alleles resulted in male-to-female sex reversal in a proportion of genotypic males. This finding suggests that neither the X-linked nor the Y-linked amh allele is responsible for male determination, but rather, amh alleles contribute to male differentiation in amphidiploid C. auratus. Subsequent research found that Amh could repress cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a) transcription in vitro, and the inhibition of cyp19a1a partially rescued the sex reversal phenotype caused by amh knockout. Besides, the amh null mutation in artificial amphitriploid C. auratus, which possesses an XXX/XXY sex determination system, also led to male-to-female sex reversal in some genotypic males. This study illustrates that the sex chromosome-residing amh is not a male-determining gene but regulates male differentiation in C. auratus, confirming the conserved function of amh in male differentiation in vertebrates.

The maturation of the gastrointestinal tract and its interconnected microbial consortia in various ruminant species is essential for their survival and productivity, as this symbiotic group plays a key role in metabolizing phyto-derived feeds into bioavailable nutrients. The rumen mucosa serves as a crucial conduit for complex host-microbiota interplay, while scarce knowledge is available regarding their co-oscillation patterns from birth to puberty. Here, we characterized th overall interaction of five age groups, from 1-day-old to 90-day-old goats. The findings indicated that the composition of the mucosa-attached microbiota underwent significant changes, with Mannheimia, Porphyromonas and Streptococcus taking the lead as the dominant genera at day 1, Akkermansia muciniphila and Lactobacillus amylovorus dominated at day 10, and a mature microbiota characterized by Succiniclasticum ruminis, Ruminococcus albus, Succinivibrio dextrinosolvens, and Fibrobacter succinogenes until day 90. Additionally, the rumen mucosa underwent a three-phase temporal shift during early life, from digestive system to immune development, and finally to nutrient metabolism. Furthermore, the integration of mucosal microbiome and host gene expression profiles uncovered a phase-specific interaction between the microbial community and host epithelium, with the early phase emphasizing digestive and immune development and the later phase focusing on enhanced nutrient metabolism. Collectively, microbiome-host co-oscillation in the rumen mucosa shaped the ruminal ecosystem during early life.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide, primarily due to the degeneration of retinal ganglion cells (RGCs). In this study, we reported vav guanine nucleotide exchange factor 2 (VAV2) as a POAG-associated gene. Through whole exome sequencing (WES) of 398 Han Chinese POAG patients and 2,010 controls, we discovered nine rare VAV2 variants linked to POAG (P_burden=1.40×l0^-6). Functional analyses revealed that these variants disrupted normal VAV2 protein function, leading to compromised cytoskeletal organization in human trabecular meshwork cells and impaired axonal growth in the 661W cell line. In vivo, Vav2 knockout mice exhibited key POAG features, including increased intraocular pressure (IOP), abnormal trabecular meshwork structure, reduced visual sensitivity, and RGC loss. This study also implicated VAV2 in the modulation of the Rho signaling pathway, which is essential for maintaining trabecular meshwork integrity and neuronal function. Taken together, this research identified VAV2 as a candidate gene for POAG and suggests VAV2 as a potential target for genetic screening of POAG diagnostics.