Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.

With the increasing incidence of male infertility, routine detection of semen is insufficient to accurately assess male fertility. Infertile men, who have lower odds of conceiving naturally, exhibit high levels of sperm DNA fragmentation (SDF). The mechanisms driving SDF include abnormal spermatogenesis, oxidative stress damage, and abnormal sperm apoptosis. As these factors can induce SDF and subsequent radical changes leading to male infertility, detection of the extent of SDF has become an efficient routine method for semen analysis. Although it is still debated, SDF detection has become a research hotspot in the field of reproductive medicine as a more accurate indicator for assessing sperm quality and male fertility. SDF may be involved in male infertility, reproductive assisted outcomes, and growth and development of offspring. The effective detection methods of SDF are sperm chromatin structure analysis (SCSA), terminal transferase-mediated dUTP end labeling (TUNEL) assay, single-cell gel electrophoresis (SCGE) assay, and sperm chromatin dispersion (SCD) test, and all of these methods are valuable for assisted reproductive techniques. Currently, the preferred method for detecting sperm DNA integrity is SCSA. However, the regulation network of SDF is very complex because the sperm DNA differs from the somatic cell DNA with its unique structure. A multitude of molecular factors, including coding genes, non-coding genes, or methylated DNA, participate in the complex physiological regulation activities associated with SDF. Studying SDF occurrence and the underlying mechanisms may effectively improve its clinical treatments. This review aimed to outline the research status of SDF mechanism and detection technology-related issues, as well as the effect of increased SDF rate, aiming to provide a basis for clinical male infertility diagnosis and treatment.

Accumulating evidence has demonstrated that lipopolysaccharide (LPS) compromises female reproduction, especially oocyte maturation and competence. However, methods to protect oocyte quality from LPS-induced deterioration remain largely unexplored. We previously found that mogroside V (MV) can promote oocyte maturation and embryonic development. However, whether MV can alleviate the adverse effects of LPS exposure on oocyte maturation is unclear. Thus, in this study, we used porcine oocytes as a model to explore the effects of MV administration on LPS-induced oocyte meiotic defects. Our findings show that supplementation with MV protected oocytes from the LPS-mediated reduction in the meiotic maturation rate and the subsequent blastocyst formation rate. In addition, MV alleviated the abnormalities in spindle formation and chromosome alignment, decrease in α-tubulin acetylation levels, the disruption of actin polymerization, and the reductions in mitochondrial contents and lipid droplet contents caused by LPS exposure. Meanwhile, LPS reduced m⁶A levels in oocytes, but MV restored these epigenetic modifications. Furthermore, MV reduced reactive oxygen species (ROS) levels and early apoptosis in oocytes exposed to LPS. In summary, our study demonstrates that MV can protect oocytes from LPS-induced meiotic defects in part by reducing oxidative stress and maintaining m⁶A levels.

Introduction: Rumen microbiota and host metabolites play a key role in regulating ruminant production performance and physiological adaptation. However, the interplay between host physiological status and rumen microbial-metabolite dynamics across lactation stages in buffaloes remains unclear.Methods: This study employed a multi-omics approach, integrating metagenomic and serum metabolomic analyses, to investigate microbial remodeling and metabolic adaptations in buffaloes during lactation and dry periods.Results: Metagenomic analysis revealed increased abundances of Anaerovibrio, Succiniclasticum, and Methanobrevibacter_A during lactation, associated with lipid hydrolysis, propionate production, and methanogenesis, respectively. Glycoside hydrolase families GH2, GH3, GH5, and GH13 were enriched, indicating elevated carbohydrate degradation potential. In contrast, Butyrivibrio, Fibrobacter, and Eubacterium_Q were predominant during the dry period, contributing to fiber degradation and butyrate synthesis. Functional pathways related to niacin metabolism, bicarbonate reabsorption, and neuroactive ligand-receptor interaction were significantly upregulated during lactation. Metabolomic profiling identified lactation-enriched metabolites such as indole-3-methylacetate, D-maltose, and gluconic acid, correlating with immune and metabolic indicators (e.g., IgA, glucose, LDL). Conversely, dry period metabolites such as 1-methylhistidine and 5-hydroxyindoleacetic acid indicated physiological shifts toward tissue repair and stress mitigation.Discussion: The integrative analysis revealed that host physiological demands during lactation coordinate rumen microbial restructuring to enhance triglyceride degradation, fatty acid biosynthesis, and energy mobilization, thereby supporting milk production. These findings provide novel insights into the host-driven microbiome-metabolite axis underlying lactation in buffaloes.

Accumulating evidence has demonstrated that benzo(a)pyrene (BaP) exposure adversely affects female reproduction, especially oocyte meiotic maturation and subsequent embryo development. Although we previously found that mogroside V (MV), a major bioactive component of S. grosvenorii, can protect oocytes from quality deterioration caused by certain stresses, whether MV can alleviate BaP exposure-mediated oocyte meiotic defects remains unknown. In this study, female mice were exposed to BaP and treated concomitantly with MV by gavage. We found that BaP exposure reduced the oocyte maturation rate and blastocyst formation rate, which was associated with increased abnormalities in spindle formation and chromosome alignment, reduced acetylated tubulin levels, damaged actin polymerization and reduced Juno levels, indicating that BaP exposure results in oocyte nucleic and cytoplasmic damage. Interestingly, MV treatment significantly alleviated all the BaP exposure-mediated defects mentioned above, indicating that MV can protect oocytes from BaP exposure-mediated nucleic and cytoplasmic damage. Additionally, BaP exposure increased intracellular ROS levels, meanwhile induced DNA damage and early apoptosis in oocytes, but MV treatment ameliorated these defective parameters, therefore it is possible that MV restored BaP-mediated oocyte defects by reducing oxidative stress. In summary, our findings demonstrate that MV might alleviate oocyte meiotic defects and quality deterioration in BaP-exposed mice.