Search Results (81,189)

Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides a comprehensive overview of the latest advancements in LNP research, focusing on preclinical safety assessments encompassing toxicity, reactogenicity, and immunogenicity. Summary and Outlook: Additionally, it outlines potential strategies for addressing these challenges and offers insights into future research directions for enhancing the application of LNPs in mRNA therapeutics. Full article

The cultivation of horticultural plants in controlled greenhouse environments is a pivotal practice in modern agriculture, offering the potential to enhance crop productivity and mitigate climate change effects. This study investigates the biomechanical properties and lignin content of various Capsicum annuum mutant lines—‘fragile-plant’ (frx), ‘tortuous internodi’ (tti), and ‘puffy-structured stem’ (pfi)—in comparison to a commercially established variety, ‘Garai Fehér’. We employed the acetyl bromide method to quantify lignin content and conducted three-point bending tests to assess rigidity in three distinct regions of the stem. Gene expression analysis of key lignin biosynthetic pathway genes (PAL, C4H, 4CL, CCoAOMT, CAD) was performed using qRT-PCR. The results revealed significant differences in lignin content and breaking force among the genotypes and stem regions. The tti mutants exhibited similar lignin content to the control but lower breaking strength, likely due to elongated internodes. The frx mutants showed uniformly reduced lignin content, correlating with their fragile stems. The pfi mutants displayed abnormally high lignin content in the top region yet demonstrated the lowest stem rigidity in every region. Overexpression of CAD and CCoAOMT was detected in the mutants in specific regions of the stem, suggesting alterations in lignin biosynthesis; however, we could not confirm the correlation between them. Our findings indicate that while lignin content generally correlates with stem rigidity, this trait is complex and influenced by more factors. Full article

Background: The giant keyhole limpet Megathura crenulata is a gastropod mollusk (Fissurella superfamily) that is endemic to the eastern Pacific coast from southern California, USA, to Baja California Sur, Mexico. M. crenulata is socioeconomically important as it produces a potent immune-stimulating protein, called Keyhole Limpet Hemocyanin, which is extracted in vivo and utilized for vaccine development. However, ecological studies are scarce and genetic knowledge of the species needs to be improved. Our objectives were to assemble and annotate the mitogenome of M. crenulata, and to assess its phylogenetic relationships with other marine gastropods and to evaluate its population genetic diversity and structure. Methods: Samples were collected for mitogenome assembly (n = 3) spanning its geographic range, Puerto Canoas (PCA) and Punta Eugenia (PEU), Mexico, and California (CAL), USA. Total DNA was extracted from gills sequenced using Illumina paired-end 150-bp-read sequencing. Reads were cleaned, trimmed, assembled de novo, and annotated. In addition, 125 samples from eight locations were analyzed for genetic diversity and structure analysis at the 16s rRNA and COX1 genes. Results: The M. crenulata mitogenomes had lengths of 16,788 bp (PCA) and 16,787 bp (PEU) and were composed of 13 protein-coding regions, 22 tRNAs, two rRNAs, and the D-Loop region. In terms of phylogeographic diversity and structure, we found a panmictic population that has experienced recent demographic expansion with low nucleotide diversity (0.002), high haplotypic diversity (0.915), and low φ_ST (0.047). Conclusions: Genetic insights into the giant keyhole limpet provides tools for its management and conservation by delimiting fishing regions with low genetic diversity and/or genetically discrete units. Full article

Dengue and other arboviruses remain a global threat, and enhanced efforts to control the mosquitoes that transmit them are urgently needed. A survey of potential manmade Aedes aegypti (L.) and Aedes albopictus (Skuse) oviposition containers was performed in four communities near the end of the typical dry season in 2018 in Trinidad, West Indies. The purpose was to conduct individual premise surveys and use GIS mapping to visualize premises within communities that had Aedes-positive containers, as this information could be used for the prioritization of mosquito control efforts in potential high risk areas as the wet season progressed. Accessible premises were surveyed following standard inspection protocols used by the Insect Vector Control Division (IVCD), Ministry of Health (MOH). The results indicated that two of the four locations would be at high risk for arbovirus transmission going into the wet season. The GIS mapping of premises with Aedes-positive containers facilitated the identification of potential hot spots for arbovirus transmission risk within communities that should be prioritized for enhanced monitoring and vector control efforts, emphasizing the need to increase community participation in standard surveys by IVCD. Full article

The market share of electric vehicles (EVs) is growing rapidly. However, given the huge demand for parking and charging of electric vehicles, supporting facilities generally have problems such as insufficient quantity, low utilization efficiency, and mismatch between supply and demand. In this study, based on the actual EV operation data, we propose a driver travel-charging demand prediction method and a fuzzy bi-objective optimization method for location and size planning of charging parking lots (CPLs) based on existing parking facilities, aiming to reduce the charging waiting time of EV users while ensuring the maximal profit of CPL operators. First, the Monte Carlo method is used to construct a driver travel-charging behavior chain and a user spatiotemporal activity transfer model. Then, a user charging decision-making method based on fuzzy logic inference is proposed, which uses the fuzzy membership degree of influencing factors to calculate the charging probability of users at each road node. The travel and charging behavior of large-scale users are then simulated to predict the spatiotemporal distribution of charging demand. Finally, taking the predicted charging demand distribution as an input and the number of CPLs and charging parking spaces as constraints, a bi-objective optimization model for simultaneous location and size planning of CPLs is constructed, and solved using the fuzzy genetic algorithm. The results from a case study indicate that the planning scheme generated from the proposed methods not only reduces the travelling and waiting time of EV users for charging in most of the time, but also controls the upper limit of the number of charging piles to save construction costs and increase the total profit. The research results can provide theoretical support and decision-making reference for the planning of electric vehicle charging facilities and the intelligent management of charging parking lots. Full article

Since the advent of germ cell transplantation (GCT), it has been widely used in shortening the fish breeding cycle, sex-controlled breeding and the protection of rare and endangered fish. In this study, the effectiveness of female sterile recipient preparation and donor stem cell isolation and purification were comprehensively evaluated for spermatogonial stem cell transplantation (SSCT) in Paralichthys olivaceus. The best way to prepare sterile recipients was found to be giving three-year-old fish four intraovarian injections of busulfan (20 mg/kg body weight) combined with exposure to a high temperature (28 °C) after the spawning season compared with the two other ways, which induced apoptosis of most of the endogenous germ cells, resulting in shrinkage of the spawning plate and enlargement of the ovarian lumen. Further analysis showed that both the gonadosomatic index and germ-cell-specific vasa expression were significantly lower than those of the natural-temperature group before treatment (p < 0.05). A high percentage (>60.00%) of spermatogonial stem cells (SSCs) were obtained after isolation and purification and were transplanted into the prepared recipients. After three weeks of SSCT, the numbers of PKH26-labeled SSCs were increased in the ovaries of the recipients. These findings provide a basis for the establishment of an ideal SSCT technique using P. olivaceus females as the recipients, ultimately contributing to the efficient conservation of male germplasm resources and effective breeding. Full article

Objectives: Achromatopsia (ACHM) is a rare autosomal, recessively inherited disease that is characterized by cone dysfunction, for which several gene therapies are currently on trial. The aim of this study was to find correlations between the morphological macular changes identified using optical coherence tomography (OCT) and some visual functional parameters. Visual acuity (VA), contrast sensitivity (CS), and macular sensitivity obtained by means of microperimetry were assessed. Methods: Adolescents with ACHM underwent macular microperimetry (S-MAIA device) in mesopic condition, macular OCT, best corrected visual acuity (BCVA), low luminance visual acuity (LLVA), near vision acuity (NVA), and CS measurement. Results: Eight patients (15 eyes) with ACHM were analyzed. The mean age was 17 ± 2.7 years, and genetic variants involved the CNGA3 gene (37.5%) and CNGB3 gene (62.5%). OCT staging significantly correlated with microperimetry sensitivity parameters, namely the sensitivity of the central foveal point (p = 0.0286) and of the first and second perifoveal rings (p = 0.0008 and p = 0.0014, respectively). No correlations were found between OCT staging and VA measurements, nor with CS value. Conclusions: Among the extensive evaluated visual function tests, only microperimetry sensitivity showed a correlation with morphological macular changes identified at OCT. Microperimetry sensitivity may thus represent a useful visual function tool in natural ACHM history studies considering the upcoming research on gene therapies for the treatment of ACHM. Full article

Spodoptera exigua is one of the most serious lepidopteran pests of global importance. With the intensive use of insecticides, S. exigua has evolved resistance to many insecticides, including the sodium channel blocker insecticides (SCBIs) indoxacarb and metaflumizone. In this study, we investigated the role of the V1848I mutation in the voltage-gated sodium channel (VGSC) in SCBI resistance and its inheritance patterns in S. exigua through the development and characterization of a near-isogenic resistant strain. The AQ-23 strain of S. exigua, collected in 2023 from Anqing, Anhui province of China, shows 165-fold resistance to indoxacarb compared with the susceptible WH-S strain. A frequency of 44.6% for the V1848I mutation was detected in the SeVGSC of the AQ-23 strain, while no F1845Y mutation was found. Through repeated backcrossing and marker-assisted selection, the V1848I mutation in the AQ-23 strain was introgressed into the susceptible WH-S strain, creating a near-isogenic strain named WH-1848I. This WH-1848I strain exhibits high levels of resistance to indoxacarb (146-fold) and metaflumizone (431-fold) but remains susceptible to broflanilide and spinosad compared with the WH-S strain. Inheritance analysis revealed that SCBI resistance in the WH-1848I strain is autosomal, nonrecessive, and genetically linked to the V1848I mutation. These findings establish a clear link between the V1848I mutation and SCBI resistance in S. exigua, offering valuable insights for developing molecular detection tools and resistance management strategies. Full article

Background/Objectives: Genetic factors contribute to the physiopathology of obesity and its comorbidities. This study aimed to investigate the association of the SNPs ABCA1 (rs9282541), ADIPOQ (rs2241766), FTO (rs9939609), GRB14 (rs10195252), and LEPR (rs1805134) with various clinical, anthropometric, and biochemical variables. Methods: The study included 396 Mexican mestizo individuals with obesity and 142 individuals with normal weight. Biochemical markers were evaluated from peripheral blood samples, and SNP genotyping was performed using PCR with TaqMan probes. A genetic risk score (GRS) was computed using an additive model. Results: No significant associations were found between the SNPs ABCA1, ADIPOQ, FTO, and LEPR with obesity. However, the T allele of the GRB14 SNP was significantly associated with obesity (χ² = 5.93, p = 0.01; OR = 1.52; 95% CI: 1.08–2.12). A multivariate linear regression model (adjusted R-squared: 0.1253; p < 0.001) predicting LDL-c levels among all participants (n = 538) identified significant (p < 0.05) beta coefficients for several anthropometric and biochemical variables, as well as for the GRS. Additionally, the interaction between the GRS and the waist-to-hip ratio (WHR) showed a negative beta coefficient (BC = −26.5307; p = 0.014). Participants with a WHR < 0.839 showed no effect of GRS on LDL-c concentration, while those with a WHR > 0.839 exhibited a greater effect of GRS (~9) at lower LDL-c concentrations (~50 mg/dL) and a lesser effect of GRS (~7) at higher LDL-c concentrations (~250 mg/dL). Conclusions: A significant interaction between genetics and WHR influences LDL-c in Mexicans, which may contribute to the prevention and clinical management of dyslipidemia and cardiovascular disease. Full article

Digital solutions in the field of restorative neurology offer significant assistance, enabling patients to engage in rehabilitation activities remotely. This research introduces ReMoVES, an Internet of Medical Things (IoMT) system delivering telemedicine services specifically tailored for multiple sclerosis rehabilitation, within the overarching framework of the STORMS project. The ReMoVES platform facilitates the provision of a rehabilitative exercise protocol, seamlessly integrated into the Individual Rehabilitation Project, curated by a multidimensional medical team operating remotely. This manuscript delves into the second phase of the STORMS pilot feasibility study, elucidating the technology employed, the outcomes achieved, and the practical, professional, and academic implications. The STORMS initiative, as the genesis of digital telerehabilitation solutions, aims to enhance the quality of life for multiple sclerosis patients. Full article

Currently, the NRC amino acid (AA) requirements for pigs published in 2012 are used as a reference in variable swine industries. However, recent results in several articles suggest that the standardized ileal digestible (SID) AA–lysine (Lys) ratio significantly evolved over the last two decades, while some publications report inconsistent outcomes. Therefore, the present study used a meta-regression analysis to assess the relative ratio to lysine to maximize the feed efficiency of four essential amino acids (tryptophan, valine, isoleucine, and methionine) in pig diets. According to the PRISMA guidelines, articles examining the target AA requirement using a basal diet supplemented with varying levels of crystalline AA (tryptophan, valine, isoleucine, or methionine) were identified across Scopus, PubMed, and Science Direct. As a result, 23, 22, 16, and 9 articles using tryptophan, valine, isoleucine, and methionine were selected and categorized into experiments for inclusion in our meta-analysis. The results suggested that the requirements of tryptophan, valine, isoleucine, and methionine in our meta-regression analysis were superior to NRC recommendations, regardless of the regression models and the growth phases with significant RSQ values (RSQ ≈ 1). Also, the QUAD and CLP regression models emphasized higher requirements than the LP model for the great majority of amino acids and growth phases. The results of the QUAD and CLP models were selected as estimations of the amino acid requirements for pigs under challenged conditions, whereas the LP model was chosen to estimate the amino acid requirements of genetically improved pigs under a modern housing system. The results of this meta-regression analysis could be used to refresh the information on the NRC amino acids (AA) requirements for swine. Full article

Surgical treatment of liver metastases of uveal melanoma (LMUM) could be proposed for selected patients. This retrospective study examined the prognostic significance of the genetic profiles of liver metastases after LMUM resection. A total of 86 patients treated with resection for LMUM, who underwent genetic analysis of liver metastasis, were included. A multivariable Cox model identified the independent predictors of recurrence-free survival (RFS) and overall survival (OS). The disease-free interval (DFI) and a chromosome 8q surgain (>3 copies) were independent predictors and categorized patients into three risk groups with distinct postoperative prognoses. For the low-, intermediate-, and high-risk scores of recurrence, the median RFS values were 15 months (95% CI: 10–22), 6 months (95% CI: 4–11), and 4 months (95% CI: 2–7), and the median OS values were 86 months (95% CI: 55-NR), 25 months (95% CI: 17–48), and 19 months (95% CI: 12–22), respectively. The predictive accuracy of this scoring system was demonstrated by a mean area under the curve (AUC(t)) of 0.77 (95% CI: 0.65–0.90) for RFS and 0.81 (95% CI: 0.70–0.92) for OS. This novel score, based on a DFI of ≤24 months combined with a chromosome 8q surgain, identifies patients at a high risk of early recurrence and could help clinicians to propose perioperative treatment. Full article

RNA interference (RNAi) is a promising approach for gene therapy in cancers, but it requires carriers to protect and deliver therapeutic small interfering RNA (siRNA) molecules to cancerous cells. Starch-based carriers, such as quaternized starch (Q-Starch), have been shown to be biocompatible and are able to form nanocomplexes with siRNA, but significant electrostatic interactions between the carrier and siRNA prevent its release at the target site. In this study, we aim to characterize the effects of the degree of substitution (DS) and molecular weight (Mw) of Q-Starch on the gene silencing capabilities of the Q-Starch/siRNA transfection system. We show that reducing the DS reduces the electrostatic interactions between Q-Starch and siRNA, which now decomplex at more physiologically relevant conditions, but also affects additional parameters such as complex size while mostly maintaining cellular uptake capabilities. Notably, reducing the DS renders Q-Starch more susceptible to enzymatic degradation by α-amylase during the initial Q-Starch pretreatment. Enzymatic cleavage leads to a reduction in the Mw of Q-Starch, resulting in a 25% enhancement in its transfection capabilities. This study provides a better understanding of the effects of the DS and Mw on the polysaccharide-based siRNA delivery system and indicates that the polysaccharide Mw may be the key factor in determining the transfection efficacy of this system. Full article