Potent and long-lasting humoral and cellular immunity against varicella zoster virus induced by mRNA-LNP vaccine.

Varicella zoster virus (VZV) is a highly contagious human herpes virus responsible for causing chickenpox (varicella) and shingles (herpes zoster). Despite the approval of a highly effective vaccine, Shingrix®, the global incidence of herpes zoster is increasing and the economic burden to the health care system and society are substantial due to significant loss of productivity and health complications, particularly among elderly and immunocompromised individuals. This is primarily because access to the vaccines remains mostly limited to countries within developed economies, such as USA and Canada. Therefore, similarly effective vaccines against VZV that are more accessible to the rest-of-the-world are necessary. In this study, we aimed to evaluate immunogenicity and memory response induced by three mRNA-LNP-based vaccine candidates targeting VZV's surface glycoprotein E (gE). C57BL/6 mice were immunized with each candidate vaccine, and humoral and cellular immune responses were assessed. Our results demonstrate that the mRNA-LNP-based vaccine candidates elicited robust and durable humoral responses specific to the gE antigen. Notably, mice vaccinated with the mRNA-LNP vaccines exhibited significantly higher antigen-specific T-cell cytokine production compared to the group receiving Shingrix®, the current standard of care vaccine. Additionally, mRNA-LNP vaccines induced long-lasting memory response, as evidenced by detection of persistent gE-specific Long-Lived Plasma Cells (LLPCs) and memory T cells four months after final immunization. These findings underscore the potential of our mRNA-LNP-based vaccine candidates in generating potent immune responses against VZV, offering promising prospects for their clinical development as an effective prophylactic vaccine against herpes zoster.

Metformin improves obesity-related oligoasthenospermia via regulating the expression of HSL in testis in mice.

Researches have proposed that obesity might contribute to development of oligoasthenospermia. This study was performed to confirm whether obesity contributes to oligoasthenospermia as well as the underlying mechanisms in mice fed with a high fat diet (HFD). Meanwhile, the actions of metformin, a drug of well-known weight-lowering effect, on sperm quality in obese mice were investigated. Our results showed that HFD feeding reduced sperm quality and steroid hormone levels in mice, associated with disruptions in testicular histomorphology and spermatogenesis. Moreover, obesity increased sperm apoptosis. These effects could be prevented by metformin treatment in HFD-fed mice. Mechanistically, an increasement in lipid contents associated with decreased hormone-sensitive lipase (HSL) protein expression in testes in HFD-fed mice was observed, which could be improved by metformin treatment. Then, the model of TM4 mouse Sertoli cells stimulated with palmitic acid (PA) was used to investigate the potential effect of lipid retention on testicular apoptosis and sperm quality reduction. In consistent, PA exposure elevated lipid contents as well as apoptosis in TM4 cells, which could also be improved by metformin treatment. Of note, the protein expression of HSL was reduced stimulated by PA in TM4 cells, also rescued by metformin. Then, anti-apoptosis effect of metformin would be lost with the deficiency of HSL. In summary, our study propose that obesity contributes to oligoasthenospermia by increasing sperm apoptosis induced by impaired lipid hydrolysis due to HSL down-regulation, which could be prevented with metformin treatment via regulating the expression of HSL in testis in mice.

Study on Improved Computed Tomography Scanning Parameters for Patients with Nasal Bone Fracture Based on ITK Three-dimensional Labelling.

OBJECTIVE: To investigate the influence of improved exposure parameters on the image quality of multi-slice spiral computed tomography in nasal bone fracture imaging. METHODS: Fifty patients with optimised parameters combined with coronal scanning were allocated to the modified group and 50 patients with routine scanning parameters to the routine group. The image quality and nasal bone display of the two groups were assessed and statistically analysed, and the quality of scanned images before and after parameter optimisation was compared. RESULTS: The optimised image quality was better than that of conventional scanning parameters. The parameters used were 120 kv, 180 mA, a layer thickness of 0.625 mm, a layer spacing of 0.312 mm, a pitch of 0.516:1, a frame speed of 1 s, a scanning field of 12 cm and a reconstructed layer thickness for scanning of 0.625 mm; the scanned image was clear, and the parameter optimisation was achieved. This ensures that the annotation data in ITK labelling is more accurate. CONCLUSION: The optimised parameters and scanned coronal plane show the nasal bone and its surrounding structures more comprehensively, which is of high diagnostic value for nasal bone fractures. The three-dimensional annotation data based on ITK is more standardised, laying a foundation for the subsequent research of artificial intelligence modelling.