Search Results (87)

The Japanese encephalitis virus is an arbovirus that causes severe damage to the central nervous system. At present, there are still 67,900 cases of Japanese encephalitis worldwide every year, which poses a global public health concern and causes great economic losses to animal husbandry. In this study, we analyzed the epidemiology, transmission, and evolution of JEV based on the NCBI database. E and NS1 were emphatically analyzed for amino acid variation and predicted protein structure. Gene recombination and the evolutionary rate of JEV were analyzed using RDP 4 and BEAST. The maximum clade credibility tree of E was reconstructed to estimate the time of the most recent common ancestor. Chinese genotype Ⅰ (GI) strain recombination events occurred in the C, M/PrM, E, NS2A, NS4B, and NS5 proteins, and genotype III (GIII) strains occurred in the E, NS1, NS3, NS4A, and NS5 proteins. The average evolutionary rates of JEV were comparable (3.3830 × 10⁻⁴, 2.0481 × 10⁻⁴, 3.5650 × 10⁻⁴, 2.2423 × 10⁻⁴, 3.0844 × 10⁻⁴, and 1.9757 × 10⁻⁴ substitutions/site/year for the JEV-I whole genome, JEV-III whole genome, JEV-I E gene, JEV-III E gene, JEV-I NS1 gene, and JEV-III NS1 gene, respectively). The MCC tree revealed the evolutionary order was GⅢ, GⅠ, GⅤ, GⅡ, and GⅣ. This study was expected to provide theoretical support for vaccine development and comprehensive prevention and treatment of JEV. Full article

Dengue virus (DENV) threatens public health, especially in regions with tropical and subtropical climates. In 2024, the World Health Organisation reported 3.4 million confirmed dengue cases, with 16,000 severe cases and 3000 dengue-associated fatalities. The first licensed dengue vaccine, CYD-TDV (Dengvaxia^®,Sanofi-Pasteur, Paris, France), is recommended by the WHO only for individuals aged 9–45 years with a prior history of dengue infection. However, being vaccinated with Dengvaxia^® increases the risk of developing severe dengue infections in seronegative individuals. Recently, a second licensed dengue vaccine, Qdenga^®,Takeda, Singen, Germany), was approved and recommended by the WHO to be administered only in highly dengue-endemic countries, as it was not shown to elicit a robust immune response against DENV-3 and DENV-4 serotypes in dengue seronegative individuals. Due to an imbalance in immune response against all four DENV serotypes, there is a higher risk of developing the antibody-dependent enhancement (ADE) effect, which could lead to severe dengue. This review has identified mutations throughout the DENV genome that were demonstrated to attenuate the virulence of DENV in either in vitro or in vivo studies. Several amino acid residues within the DENV prM and E proteins were identified to play important roles in ADE and modifying these ADE-linked residues is important in the rational design of novel live-attenuated dengue vaccine candidates. This review provides current insights to guide the development of a novel live-attenuated tetravalent dengue vaccine candidate that is effective against all DENV serotypes and safe from ADE. The efficacy and safety of the live-attenuated vaccine candidate should be further validated in in vivo studies. Full article

Background: Cassava mosaic disease (CMD), caused by the Sri Lankan cassava mosaic virus (SLCMV), significantly increases cassava yield losses in Thailand, with losses ranging from 30% to 80%, and is exacerbated by limited access to healthy planting materials. Methods: This study explored salicylic acid (SA) as a potential treatment for enhancing disease resistance in CMD infected cassava plants. SA was applied at 100 and 200 mg/mL, and its effects were evaluated using quantitative real-time polymerase chain reaction (qPCR) and reverse transcription qPCR (RT-qPCR) to measure viral loads and the expression levels of resistance genes. Results: Although SA treatment did not considerably affect disease severity, foliar CMD symptoms visibly decreased, particularly with 200 mg/mL SA, which also reduced SLCMV particle counts at 1- and 2-weeks post-treatment. SA upregulated the expression of pathogenesis-related proteins (PRs), including HSP90.9, WRKY59, SRS1, and PR9e. Additionally, SA enhanced the regulation of secondary metabolite pathways involving L-serine within the glycine, serine, and threonine metabolism, as well as the phenylpropanoid biosynthesis pathways. Conclusions: These findings collectively indicate that SA enhances resistance through the systemic acquired resistance (SAR) pathway and can serve as a potential strategy for the management of CMD, particularly in regions where healthy cassava planting materials are scarce. The study highlights the efficacy of SA in reducing viral particles, inducing the immune response, and providing a promising approach for controlling CMD. Full article

The birch pollen allergen Bet v 1 is believed to be the main sensitizer among PR-10 allergens. Recent data have shown that some other PR-10 allergens also display sensitization activities, and Bet v 1-based immunotherapy is not effective for blocking allergic reactions to PR-10 proteins with low similarities to Bet v 1. Here, we investigated the sensitization potential of the major soybean allergen Gly m 4 and its cross-reactivity with Bet v 1. We demonstrated that Gly m 4 bound cholesterol and bile acids, including deoxycholic acid (DCA). Using qPCR, we showed that Gly m 4 induced the expression of genes encoding alarmins TSLP and IL-33 in intestinal-like Caco-2 cells; however, its fragments resulting from digestion by gastroduodenal enzymes or the DCA-bound Gly m 4 caused more pronounced gene upregulation. Using competitive ELISA, we demonstrated the low cross-reactivity of anti-Gly m 4 and anti-Bet v 1 IgG, raised in laboratory animals. Using mice allergy models with sensitization to birch or soybean allergens, we also showed a low cross-reactivity of Gly m 4- and Bet v 1-specific IgE, IgG1 and IgG2a. Thus, our findings support an assumption of the intrinsic sensitization capacity of Gly m 4 and the existence of Gly m 4-specific antibodies in sera of allergic patients. Full article

Background: This study aimed to investigate genetic variants associated with the estimated glomerular filtration rate (eGFR) and their interactions with lifestyle factors and bioactive compounds in large hospital-based cohorts, assessing their impact on renal dysfunction risk. Methods: Participants were categorized into two groups based on eGFR: High-GFR (control; n = 51,084) and Low-GFR (renal dysfunction; n = 7617), using an eGFR threshold of 60 mL/min/1.73 m². Genetic variants were identified through a genome-wide association analysis, and their interactions with lifestyle factors were assessed a using generalized multifactor dimensionality reduction (GMDR) analysis. Additionally, interactions between polygenic risk scores (PRS) and nutrient intake were examined. Results: Low eGFR was associated with higher urinary protein levels (4.67-fold) and correlated with a Western-style diet and with saturated fat, arginine, and isoleucine intakes but not sodium intake. The genetic model for low eGFR included variants linked to energy production and amino acid metabolism, such as rs1047891_CPS1, rs3770636_LRP2, rs5020545_SHROOM3, rs3812036_SLC34A1, and rs4715517_HCRTR2. A high PRS was associated with a 1.78-fold increased risk of low eGFR after adjusting for sociodemographic and lifestyle factors. The PRS from the 6-SNP model interacted with plant-based diets (PBDs) and coffee intake, where individuals with higher PBD and coffee consumption had a lower risk of renal dysfunction. Additionally, CPS1 rs1047891 interacted with vitamin D intake (p = 0.0436), where the risk allele was linked to lower eGFR with low vitamin D intake but not with high intake. Molecular docking showed that vitamin D3 had a lower binding energy to the CPS1 mutant type (−9.9 kcal/mol) than the wild type (−7.5 kcal/mol), supporting a potential gene–nutrient interaction influencing renal function. Conclusions: Middle-aged and elderly individuals with a high genetic risk for renal dysfunction may benefit from a plant-based diet, moderate coffee consumption, and sufficient vitamin D intake. Full article

The ubiquitination and degradation of proteins are widely involved in plant biotic and abiotic stress responses. E3 ubiquitin ligases play an important role in the ubiquitination of specific proteins. In this study, we identified the function of a U-box E3 ubiquitin ligase gene OsPUB57 in rice. Expression analyses revealed that OsPUB57 was mainly expressed in the aboveground part of rice. Drought, salt, cold, JA (jasmonic acid), PAMPs (pathogen-associated molecular patterns) or Magnaportheoryzae treatment could significantly suppress the expression of OsPUB57 in rice. Compared with wild-type plants, OsPUB57-overexpressing plants showed a decrease in resistance to M. oryzae, while the mutant plants exhibited an enhancement of M. oryzae resistance. The expression level detection indicated that OsPUB57 negatively regulates rice blast resistance, probably by down-regulating the expression of the defense-related genes OsPR1a and OsAOS2. This study provides a candidate gene for the genetic improvement of rice blast resistance. Full article

Familial hemiplegic migraine (FHM) is characterized by repeated episodes of reversible localized neurological deficits, in addition to headache. The aura of HM includes visual, sensory, motor, and verbal symptoms. Hemiplegic migraine (HM) is classified into non-familial sporadic HM (SHM) and familial HM (FHM). Here, we analyzed the clinical symptoms and their relevance in four Japanese patients considered to have SCN1A mutations as a cause. Sequencing of SCN1A was performed using a whole exome sequence method in 48 blood samples from clinically suspected patients with FHM. Subsequently, algorithm analysis, allele frequency determination, and three-dimensional structure analysis of the recognized variants were performed, and the recognized variants were evaluated. We found five heterozygous missense mutations (p.A23E, p.V250L, p.T398M, p.R1575C, p.L1660I) in SCN1A, three of which had not been reported. These five mutations may also affect the structure of the protein products, as assessed using a three-dimensional structural analysis. In all cases, the clinical symptoms included visual, sensory, motor, and verbal symptoms, which are forms of aura. Similarities were detected, such as the appearance of symptoms at a young age and other symptoms, such as hemiplegia after a headache attack. We report five missense mutations in SCN1A of Japanese cases. Full article

Hypothyroidism causes ovarian dysfunction and infertility in women and animals and impairs the hypothalamic expression of kisspeptin (Kp). However, kisspeptin is also expressed in the genital system, and the lack of the Kp receptor (Kiss1r) in the uterus is linked to reduced implantation rates. This study investigated the impact of hypothyroidism on the uterine expression of Kp and Kiss1r in female rats throughout the estrous cycle and the associated changes in uterine activity modulators. Hypothyroidism was induced through daily administration of propylthiouracil (PTU) over a period of 14 days. Plasma levels of LH, E₂, and P₄, cyclicity, body and uterine weight, uterine histomorphometry, and the gene and/or protein expression of Kiss1, Kiss1r, estrogen receptor α (ERα), progesterone receptor (PR), and thyroid hormone receptor α (TRα) were assessed. Additionally, proliferative activity (CDC-47) and the gene expression of uterine receptivity mediators (SMO, WNT4, BMP2, HAND2, MUC1, and LIF) were evaluated. Hypothyroidism prolonged the diestrus and increased progesterone levels during this phase, while decreasing luteinizing hormone and estradiol on proestrus. In the uterus, hypothyroidism reduced Kp immunostaining on diestrus and KISS1R mRNA levels on proestrus. These changes were accompanied by reduced endometrial glands, reduced uterine proliferative activity, and reduced ERα gene and protein expression. Additionally, hypothyroidism led to reduced uterine gene expression of LIF, BMP2, WNT4, and HAND2. On the other hand, thyroid hypofunction increased uterine PR and TRα immunostaining, while it reduced PGR gene expression on diestrus. These findings demonstrate that hypothyroidism reduces the expression of Kiss1/Kiss1r system in the uterus, which is associated with disrupted uterine estrogen and progesterone signaling and reduced expression of uterine receptivity mediators across the rat estrous cycle. Full article

Zika virus (ZIKV) is a medically important mosquito-borne orthoflavivirus, but no vaccines are currently available to prevent ZIKV-associated disease. In this study, we compared three recombinant chimeric viruses developed as candidate vaccine prototypes (rJEV/ZIKV^MR-766, rJEV/ZIKV^P6-740, and rJEV/ZIKV^PRVABC-59), in which the two neutralizing antibody-inducing prM and E genes from each of three genetically distinct ZIKV strains were used to replace the corresponding genes of the clinically proven live-attenuated Japanese encephalitis virus vaccine SA₁₄-14-2 (rJEV). In WHO-certified Vero cells (a cell line suitable for vaccine production), rJEV/ZIKV^P6-740 exhibited the slowest viral growth, formed the smallest plaques, and displayed a unique protein expression profile with the highest ratio of prM to cleaved M when compared to the other two chimeric viruses, rJEV/ZIKV^MR-766 and rJEV/ZIKV^PRVABC-59, as well as their vector, rJEV. In IFNAR^−/− mice, an animal model of ZIKV infection, subcutaneous inoculation of rJEV/ZIKV^P6-740 caused a low-level localized infection limited to the spleen, with no clinical signs of infection, weight loss, or mortality; in contrast, the other two chimeric viruses and their vector caused high-level systemic infections involving multiple organs, consistently leading to clear clinical signs of infection, rapid weight loss, and 100% mortality. Subsequently, subcutaneous immunization with rJEV/ZIKV^P6-740 proved highly effective, offering complete protection against a lethal intramuscular ZIKV challenge 28 days after a single-dose immunization. This protection was specific to ZIKV prM/E and likely mediated by neutralizing antibodies targeting ZIKV prM/E. Therefore, our data indicate that the chimeric virus rJEV/ZIKV^P6-740 is a highly promising vaccine prototype for developing a safe and effective vaccine for inducing neutralizing antibody-mediated protective immunity against ZIKV. Full article

The present study endeavored to tackle the challenges posed by limited diversity in oat varieties and suboptimal nitrogen fertilizer utilization in the arid landscapes of the Loess Plateau. We selected three oat varieties, including early-maturing oats (E), medium-maturing oats (M), and late-maturing oats (L). In 2022, four nitrogen applications were set up as CK (0 kg N ha⁻¹), N1 (60 kg N ha⁻¹), N2 (90 kg N ha⁻¹), and N3 (120 kg N ha⁻¹). We introduced two additional nitrogen applications, N4 (180 kg N ha⁻¹) and N5 (240 kg N ha⁻¹), in 2023. The two-year study results demonstrated a significant increase in oat yield due to nitrogen application (p < 0.05). The highest grain yield was observed for E oats at 2216.63 kg·ha⁻¹ under the N3 treatment, while M and L oats had the highest grain yields at 2505.43 kg·ha⁻¹ and 2946.30 kg·ha⁻¹ under N4, respectively. The protein content of L oats reached a peak of 14.15% under N4, and the order of protein contents in oat protein components was globulin > gliadin> glutenin > albumin. The β-glucan content of L oats reached a peak of 4.92% under N3. The nitrogen fertilizer utilization efficiency (NFUE) of the three oats was highest under N2. L oats exhibited enhanced NFUE owing to an elevated pre-flowering nitrogen translocation amount (PrNTA), with a 42.94% and 29.51% increase relative to E and M oats, respectively. The pre-flowering nitrogen translocation contribution (PrNTC) in oats surpassed the post-flowering nitrogen accumulation contribution (PoNAC). Therefore, nitrogen application positively impacted oat growth, yet excessive application had an inhibitory effect. There is a significant positive correlation among oat yield, quality, nitrogen accumulation, and utilization efficiency. In summary, oat crops exhibited optimal performance in terms of yield, quality, and nitrogen use efficiency when nitrogen application rates ranged between 90 and 180 kg·ha⁻¹. Late-maturing oats coincide with the rainy and hot season in the northern dryland regions, making them more suitable for planting in the dryland areas of the Loess Plateau. Full article

Influenza is a highly contagious respiratory disease, resulting in an estimated 3 to 5 million cases of severe illness annually. While most influenza vaccines are administered parenterally via injection, one shortcoming is that they do not generate a strong immune response at the site of infection, which can become important in a pandemic. Intranasal vaccines can generate both local and systemic protective immune responses, can reduce costs, and enhance ease of administration. Previous studies showed that parenterally administered outer membrane vesicles (OMVs) that carry sequences of the M2e protein (OMV-M2e) protect against influenza A/PR8 challenge in mice and ferrets. In the current study, we measured the effectiveness of the intranasal route of the OMV-M2e vaccine against the influenza A/PR8 strain in mice. We observed high anti-M2e IgG and IgA titers post-challenge in mice vaccinated intranasally with OMV-M2e. In addition, we observed a Th1/Tc1 bias in the vaccinated mice, and an increased Th17/Tc17 response, both of which correlated with survival to A/PR8 challenge and significantly lower lung viral titers. We conclude that the intranasal-route administration of the OMV-M2e vaccine is a promising approach toward generating protection against influenza A as it leads to an increased proinflammatory immune response correlating with survival to viral challenge. Full article

Following metastatic spread, many hormone receptor positive (HR⁺) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR⁺ breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure on representative HR⁺ breast cancer cell lines through protein and gene expression analysis. Proteomics results demonstrated that 540 total proteins and 1473 phospho-proteins significantly changed due to FSS exposure and pathways of interest included early and late estrogen response. The impact of FSS on response to 17β-estradiol (E2) was next evaluated and gene expression analysis revealed repression of ER and E2-mediated genes (PR and SDF1) following exposure to FSS. Western blot demonstrated enhanced phosphorylation of mTOR following exposure to FSS. Taken together, these studies provide initial insight into the effects of FSS on HR signaling in metastatic breast cancer. Full article

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E₄) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E₄ on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E₄ was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E₄ significantly reduced the volume (p < 0.001) and weight (p < 0.05) of ectopic lesions. Histologically, E₄ did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) (p < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, p < 0.05) and increased lipid peroxidation (TBARS/MDA, p < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased (p < 0.05) and mRNA expression of Esr2 reduced (p < 0.05), in contrast with the increased expression of Esr1 (p < 0.01) and Pgr (p < 0.05). The present study demonstrates for the first time that E₄ limited the development and progression of endometriosis in vivo. Full article

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials. Full article

Serine/arginine-rich splicing factors (SRSFs) are a family of proteins involved in RNA metabolism, including pre-mRNA constitutive and alternative splicing. The role of SRSF proteins in regulating mitochondrial activity has already been shown for SRSF6, but SRSF4 altered expression has never been reported as a cause of bone marrow failure. An 8-year-old patient admitted to the hematology unit because of leukopenia, lymphopenia, and neutropenia showed a missense variant of unknown significance of the SRSF4 gene (p.R235W) found via whole genome sequencing analysis and inherited from the mother who suffered from mild leuko-neutropenia. Both patients showed lower SRSF4 protein expression and altered mitochondrial function and energetic metabolism in primary lymphocytes and Epstein–Barr-virus (EBV)-immortalized lymphoblasts compared to healthy donor (HD) cells, which appeared associated with low mTOR phosphorylation and an imbalance in the proteins regulating mitochondrial biogenesis (i.e., CLUH) and dynamics (i.e., DRP1 and OPA1). Transfection with the wtSRSF4 gene restored mitochondrial function. In conclusion, this study shows that the described variant of the SRSF4 gene is pathogenetic and causes reduced SRSF4 protein expression, which leads to mitochondrial dysfunction. Since mitochondrial function is crucial for hematopoietic stem cell maintenance and some genetic bone marrow failure syndromes display mitochondrial defects, the SRSF4 mutation could have substantially contributed to the clinical phenotype of our patient. Full article