A spike-based mRNA vaccine that induces durable and broad protection against porcine deltacoronavirus in piglets.

Coronaviruses (CoVs) are important pathogens for humans and other vertebrates, causing severe respiratory and intestinal infections that have become a threat to public health because of the potential for interspecies transmission between animals and humans. Therefore, the development of safe, effective vaccines remains a top priority for the control of CoV infection. The unique immunological characteristics of vaccines featuring messenger RNA (mRNA) present an advantageous tool for coronavirus vaccine development. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines: one encoding full-length spike (S) protein and the other encoding the spike ectodomain (Se) from porcine deltacoronavirus (PDCoV). Fourteen days after primary immunization, both mRNA vaccines induced high levels of immunoglobulin G and neutralizing antibodies in mice, with the S vaccine showing better performance than the Se vaccine. Passive immune protection of the S mRNA vaccine in suckling piglets was confirmed by the induction of robust PDCoV-specific humoral and cellular immune responses. The S mRNA vaccine also showed better protective effects than the inactivated vaccine. Our results suggest that the novel PDCoV-S mRNA-LNP vaccine may have the potential to combat PDCoV infection. IMPORTANCE: As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection.

Comparison of Clinical Outcomes, Radiological Outcomes and Bone Remodeling Outcomes Between Proximal Coated Single-Wedge New Stem and Full Coated Dual-Wedge Classic Stem in 1-Stage Bilateral Total Hip Arthroplasty.

BACKGROUND This retrospective study investigated the clinical outcomes, radiological outcomes, and bone remodeling patterns associated with a Medial/Lateral Taper (M/L Taper) stem and Link Classic Uncemented (LCU) stem in 1-stage bilateral total hip arthroplasty (THA). MATERIAL AND METHODS The results of 52 patients who underwent 1-stage bilateral THA with a M/L Taper stem on one side and an LCU stem on the other between January 2012 and February 2015 were retrospectively compared. Patients were clinically assessed by the Harris hip score (HHS), visual analogue score (VAS) and incidence of complications. Radiological indicators were measured. Periprosthetic bone remodeling was assessed via bone mineral density (BMD) measurements. RESULTS The mean follow-up time was 5.2 years. At each follow-up, there was no difference in the HHS and VAS between the 2 groups. The neck-shaft angle, offset, vertical height of the rotational center and limb lengthening were lower in the M/L Taper group than in the LCU group (P<0.001). The Engh total score was lower in the LCU group (P=0.039). Significantly higher (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 1, 2, and 6. significantly lower (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 3 and 5. CONCLUSIONS Due to the increased postoperative neck-shaft angle, the full coated dual-wedge classic stem was prone to cause lower limb lengthening. The proximal coated single-wedge new stem patients were more likely to have an insufficient postoperative neck length. The new stem achieved load transfer and proximal fixation, leading to better proximal femoral bone preservation is more in line with human biomechanical characteristics.

PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge.

Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes severe diarrhea in neonatal piglets, which is associated with a high mortality rate. Thus, developing effective and safe vaccines remains a top priority for controlling PEDV infection. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines encoding either the full-length PEDV spike (S) protein or a multiepitope chimeric spike (Sm) protein. We found that the S mRNA-LNP vaccine was superior to the Sm mRNA-LNP vaccine at inducing antibody and cellular immune responses in mice. Evaluation of the immunogenicity and efficacy of the S mRNA vaccine in piglets confirmed that it induced robust PEDV-specific humoral and cellular immune responses in vivo. Importantly, the S mRNA-LNP vaccine not only protected actively immunized piglets against PEDV but also equipped neonatal piglets with effective passive anti-PEDV immunity in the form of colostrum-derived antibodies after the immunization of sows. Our findings suggest that the PEDV-S mRNA-LNP vaccine is a promising candidate for combating PEDV infection.IMPORTANCEPorcine epidemic diarrhea virus (PEDV) continues to harm the global swine industry. It is important to develop a highly effective vaccine to control PEDV infection. Here, we report a PEDV spike (S) mRNA vaccine that primes a potent antibody response and antigen-specific T-cell responses in immunized piglets. Active and passive immunization can protect piglets against PED following the virus challenge. This study highlights the efficiency of the PEDV-S mRNA vaccine and represents a viable approach for developing an efficient PEDV vaccine.

STO and GA negatively regulate UV-B-induced Arabidopsis root growth inhibition.

Studies on UV-B-induced plant photomorphogenesis mainly focus on Arabidopsis shoots (hypocotyl, leaf, petiole, and stem) but less on roots. In the present research, the low-level UV-B (0.2 W·m-2) induced a decrease in the number of root cells in the meristem zone and an inhibition of the cell length in the maturation zone of roots in Arabidopsis thaliana L.Heynh (Col-0). UV-B-induced root growth inhibition was recovered by the addition of GA3 to culture media. GA3 played an important role in UV-B-induced inhibition of root growth. The cop1-4 mutant with more meristem cell and longer mature cells exhibited longer root length under low-level UV-B. COP1 acted as a positive regulator of root growth under UV-B, through regulation of cell division and elongation. The sto mutant exhibited a shorter root length under UV-B with similar cell length but fewer meristem cells compared with wild type (Col-0). STO only regulated cell division, but cell expansion was not affected. UV-B radiation also inhibited the root growth of uvr8 mutant, and the degree of inhibition was greater than for wild type (Ler). UV-B inhibited the growth of Arabidopsis root, possibly because it changes the GA signal and inhibited cell division and cell elongation, which be related to COP1 and STO genes.

Relationships between the femoral neck-preserving ratio and radiologic and clinical outcomes in patients undergoing total-hip arthroplasty with a collum femoris-preserving stem.

The femoral neck-preserving ratio is crucial in arthroplasty with a collum femoris-preserving (CFP) stem. The aim of our study was to analyze the relationships between the neck-preserving ratio and the short-term radiologic and clinical outcomes of patients who underwent total-hip arthroplasty (THA) with a CFP stem.The data of 325 hips from January 2015 to December 2016 were retrospectively reviewed. The demographic and radiologic data before and after surgery were obtained from patients. The neck-preserving ratio was defined as the ratio of the preserved femoral neck length to the preoperative femoral neck length. Correlations between the neck-preserving ratio and the radiologic and clinical outcomes of patients were analyzed.The mean neck-preserving ratio was 66.38 ±â€Š6.91% in the current study. We divided patients into 3 groups according to the neck-preserving ratio: group A (neck-preserving ratio ≤60.00%), group B (60.00% < neck-preserving ratio < 70.00%), group C (neck-preserving ratio ≥70.00%). Radiologic features, including the neck-shaft angle ratio (0.96 ±â€Š0.05), canal fill ratio (0.64 ±â€Š0.07), anterior-posterior offset ratio (1.04 ±â€Š0.10), and lateral offset ratio (2.55 ±â€Š1.56) (ratios of the postoperative values to the preoperative values), and the prevalence of complications was significantly different among the groups (χ = 21.173, P < .001). In the correlation analysis, we found a moderate negative correlation between the neck-preserving ratio and neck-shaft angle ratio (r = -0.308, P < .001) and a slight positive correlation of the neck-preserving ratio with the anterior-posterior offset ratio (r = 0.415, P < .001) and the lateral offset ratio (r = 0.164, P = .003). In the linear regression analyses, the neck-preserving ratio was significantly linearly correlated with the neck-shaft angle ratio (B = -0.232, 95% confidence interval [CI] = -0.311 to -0.154, P < .001), anterior-posterior offset ratio (B = 0.589, 95% CI = 0.447-0.730, P < .001), and lateral offset ratio (B = 3.693, 95% CI = 1.256-6.131, P = .003). However, there was no significant linear correlation between the neck-preserving ratio and the canal fill ratio (B = 0.073, 95% CI = -0.033 to 0.180, P = .174). Logistic regression analyses also showed that a sufficient neck-preserving ratio was a protective factor for periprosthetic femoral fractures (odds ratio [OR] = 0.924, 95% CI = 0.859-0.994, P = .035), dislocations (OR = 0.892, 95% CI = 0.796-0.999, P = .048), and thigh pain (OR = 0.886, 95% CI = 0.818-0.960, P = .003).For CFP stems, an insufficient neck-preserving ratio is significantly correlated with poor radiologic and clinical outcomes. Therefore, surgeons should be cognizant to preserve a sufficient femoral neck length during surgery to improve the outcomes for patients undergoing THA with CFP stems.