Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age‐related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed. Additionally, a significant increase in the number of ovarian follicles in aging individuals was noted. Scanning electron microscopy data indicated that NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells, suggesting potential targets and mechanisms. Transcriptomic analysis and validation experiments collectively suggested that the beneficial effects of NMN on aging ovaries are mediated through enhanced mitochondrial function, improved energy metabolism, and reduced inflammation levels. Our results suggest that NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology.

The profiles of muscle and joint pain throughout the menopausal transition and the factors associated with these symptoms have not been determined. A total of 609 participants from a longitudinal cohort study conducted in an urban Chinese community were enrolled in this study. We assessed the prevalence of musculoskeletal symptoms at different menopausal stages and explored the factors associated with these symptoms. The prevalence and severity of muscle and joint pain increase as menopausal stages progress, and late menopausal transition may be a crucial timepoint that triggers the onset of musculoskeletal pain. The results of the multivariate analysis revealed that poor health status (OR = 2.245, 95% CI = 1.714-2.94, P < 0.001), body mass index (BMI) (OR = 1.046, 95% CI = 1.01-1.084, P = 0.011), the presence of anxiety (OR = 1.601, 95% CI = 1.211-2.117, P < 0.001), and depression (OR = 1.368, 95% CI = 1.143-1.639, P < 0.001) were independently associated with muscle and joint pain. In addition, the severity of musculoskeletal pain was related to poor health status (OR = 2.738, 95% CI = 1.91-3.924, P < 0.001) and depression (OR = 1.371, 95% CI = 1.095-1.718, P = 0.006). Musculoskeletal symptoms are frequent somatic symptoms experienced by Chinese middle-aged women. Women with poor health status, high BMI, anxiety, and depression were at heightened risk of experiencing musculoskeletal pain. The severity of pain increased over time.

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies.

Cancer is one of the major global health burdens, and more effective treatments are needed. At present, there are surgery, targeted therapy, and immunotherapy for the treatment of tumors, but due to the limitations of diagnostic technology and drug resistance, surgery and targeted therapy have little effect. Active immunization in the field of immunotherapy can mobilize host immunity, trigger tumor-specific T-cell responses, and produce targeted cytotoxicity. Its efficacy largely depends on the targeted delivery efficiency of cancer vaccines. Although immunotherapy is more durable than other approaches, immunosuppression in the tumor microenvironment and immune evasion by malignant cells limit the therapeutic efficacy of cancer vaccines. To overcome these challenges, this review summarizes key strategies for improving vaccine vector targeting, as well as recent advances and trends in delivery systems.

Therapeutic cancer vaccines are a new growth point of biomedicine with broad industrial prospects in the post-COVID-19 era. Many large international pharmaceutical companies and emerging biotechnology companies are deploying different tumor therapeutic cancer vaccine projects, focusing on promoting their clinical transformation, and the vaccine industry has strong momentum for development. Such vaccines are also the core engine and pilot site for the development of new vaccine targets, new vectors, new adjuvants, and new technologies, which play a key role in promoting the innovation and development of vaccines. Various therapeutic cancer vaccines, such as viral vector vaccines, bacterial vector vaccines, cell vector vaccines, peptide vaccines, and nucleic acid vaccines, have all been applied in clinical research. With the continuous development of technology, therapeutic cancer vaccines are evolving towards the trends of precise antigens, efficient carriers, diversified adjuvants, and combined applications. For instance, the rapidly advancing mRNA-4157 vaccine is a typical representative that combines personalized antigens with efficient delivery vectors (lipid nanoparticles, LNPs), and it also shows synergistic advantages in melanoma patients treated in combination with immune checkpoint inhibitors. In this article, we will systematically discuss the current research and development status and clinical research progress of various therapeutic cancer vaccines.

BACKGROUND: Transverse tubules (TTs) are tubular invaginations of myocyte membrane forming junctions with sarcoplasmic reticulum and are essential for excitation-contraction coupling. Although it is known that TTs begin to develop 2 weeks after birth in rodent cardiomyocytes, the spatial profile and molecular mechanisms of TT morphogenesis are not clear. Understanding the molecular mechanism of TT morphogenesis may provide potential solutions for TT loss in pathogenic conditions such as hypertrophy and heart failure. METHODS: To understand early stage morphogenesis of cardiac TTs, we utilized a scanning electron microscope equipped with a focused ion beam to reconstruct a 3-dimensional spatial profile of developing TT network in cardiomyocytes from 2-week-old rats. We created tamoxifen-inducible cardiac-specific knockout rats to explore the role of exons 11 and 13 of the BIN1 (bridging integrator 1) gene. RESULTS: We found that TTs began to develop as intracellular membrane hubs around Z-discs, from which pseudopod-like tubules budded in a relatively random way toward different directions without necessarily connecting to the cell surface. A tubule network forms when membrane branches from adjacent hubs are interconnected. Cardiac-specific knockout of BIN1 exon 13 (13KO) suppressed TT microfolds. In contrast, cardiac-specific knockout of BIN1 exon 11 (11KO), which encodes the PIBM (phosphoinositide-binding motif), suppressed the formation of budding tubules, resulting in a sparse tubule network with swollen membrane hubs. Due to the underdeveloped TT network, TT-sarcoplasmic reticulum couplon density/size and excitation-contraction coupling gain in 11KO cardiomyocytes were decreased, similar to those occurring in failing heart cells. CONCLUSIONS: TTs start to develop as budding tubules branching from membrane hubs around Z-discs. This process depends at least partially on the tubulation function of pBIN1 (BIN1 isoforms with PIBM [Bin1+11 and Bin1+11+17]), which is constitutively expressed in rat and human cardiomyocytes. Defective TT morphogenesis due to altered BIN1 splicing in cardiomyocytes may have potential implications in heart diseases.