Search Results (158)

Background: In response to the emergence of immune-evasive variants of SARS-CoV-2, this study explores a novel heterologous vaccination strategy using a microparticulate formulation approach that is delivered via oral dissolving film (ODF) formulations into the buccal cavity. Heterologous administration has the potential to generate cross-reactive antibodies, which can be especially beneficial against viruses with ever-mutating variants. Moreover, the microparticulate oral dissolving film-based vaccine approach is a non-invasive vaccine delivery platform. Methods: The vaccine design incorporated whole inactivated Delta and Omicron variants of the virus, administered at prime and booster doses, respectively, effectively encapsulated in a Poly(lactic-co-glycolic) acid (PLGA) polymer matrix, and adjuvanted with Alum to enhance immune activation. Following vaccination, serum, mucosal, and tissue samples were analyzed to evaluate humoral and cellular immune responses against the model antigen, as well as other variants such as Alpha and Beta variants, to understand the cross-reactive response. Result: In vitro evaluations confirmed the vaccine’s safety and its ability to stimulate immune responses. On administering microparticulate oral dissolving films to mice, whole inactivated delta and omicron variant-specific antibodies were observed in serum samples along with neutralizing titers in terminal week. The formulated vaccine showed significant secretory IgA antibody levels in mucosal samples. Moreover, CD4⁺ and CD8a cellular responses were observed in tissue samples of spleen and lymph nodes, along with antibodies (IgG, IgA, and IgM) detected in lung supernatant samples. Humoral and cellular cross-reactive antibodies were observed in the samples. Conclusions: This approach offers a promising platform for developing next-generation vaccines capable of inducing broad immunity. Full article

Unmanned aerial vehicle (UAV)-captured RGB imagery, with high spatial resolution and ease of acquisition, is increasingly applied to individual tree crown detection (ITCD). However, ITCD in dense subtropical forests remains challenging due to overlapping crowns, variable crown size, and similar spectral responses between neighbouring crowns. This paper investigates to what extent the ITCD accuracy can be improved by using dual-seasonal UAV-captured RGB imagery in different subtropical forest types: urban broadleaved, planted coniferous, and mixed coniferous–broadleaved forests. A modified YOLOv8 model was employed to fuse the features extracted from dual-seasonal images and perform the ITCD task. Results show that dual-seasonal imagery consistently outperformed single-seasonal datasets, with the greatest improvement in mixed forests, where the F1 score range increased from 56.3%–60.7% (single-seasonal datasets) to 69.1%–74.5% (dual-seasonal datasets) and the AP value range increased from 57.2%–61.5% to 70.1%–72.8%. Furthermore, performance fluctuations were smaller for dual-seasonal datasets than for single-seasonal datasets. Finally, our experiments demonstrate that the modified YOLOv8 model, which fuses features extracted from dual-seasonal images within a dual-branch module, outperformed both the original YOLOv8 model with channel-wise stacked dual-seasonal inputs and the Faster R-CNN model with a dual-branch module. The experimental results confirm the advantages of using dual-seasonal imagery for ITCD, as well as the critical role of model feature extraction and fusion strategies in enhancing ITCD accuracy. Full article

The discovery of extensive layered witherite (BaCO₃) deposits in the Early Cambrian strata in South China offers valuable insights into the unique paleo-marine environment of this region. Based on stratigraphy, petrography, geochemistry, fluid inclusions, and pervious published multi-isotope geochemical analysis, we aim to explore the distinct genesis mechanism of the witherite deposits in the Chengkou area of South China and unveil the specific paleo-marine environment during their formation. This study concludes that the wide ⁸⁷Sr/⁸⁶Sr ratios (0.708266 to 0.708504) of witherite and barytocalcite (BaCa(CO₃)₂) support the seawater-derived barium. Negative δ¹³C values (−15.6 to −12.5‰) indicate the involvement of organic matter during the formation of witherite. The complex vapor-phase (including CH₄, H₂S, etc.) and HS⁻-containing liquid-phase compositions in the primary liquid–vapor inclusions of the witherite and barytocalcite imply that the two minerals are formed in sulfur-rich euxinic seawater. The broad homogenization temperatures are generated by thermal re-equilibration of the inclusions, rather than the actual temperatures of the trapped fluids. The salinity range of fluid inclusions in the Bashan witherite deposit (0.2 to 16.2 wt.%) records mixing between moderate-salinity basinal-derived fluids and low-salinity seawater-sourced fluids. We propose that the formation of Chengkou witherite deposits is linked to a sulfate-limited euxinic seawater environment, highlighting the spatiotemporal heterogeneity in Early Cambrian paleo-oceanic sulfate concentrations. Full article

With the continuous expansion of urban rail transit networks, construction safety of connecting passages—as critical weak links in underground structural systems—has become pivotal for project success. Although artificial ground freezing technology effectively addresses adverse geological conditions (e.g., high permeability and weak self-stability), it is influenced by multi-field coupling effects (temperature, stress, and seepage fields), which may trigger chain risks such as freezing pipe fractures and frozen curtain leakage during construction. This study deconstructed the freezing method workflow (‘drilling pipe-laying → active freezing → channel excavation → structural support’) and established a hierarchical evaluation index system incorporating geological characteristics, technological parameters, and environmental impacts by considering sandy soil phase-change features and hydro-thermal coupling effects. For weight calculation, the Analytic Hierarchy Process (AHP) was innovatively applied to balance subjective-objective assignment deviations, revealing that the excavation support stage (weight: 52.94%) and thawing-grouting stage (31.48%) most significantly influenced overall risk. Subsequently, a Bayesian network-based risk assessment model was constructed, with prior probabilities updated in real-time using construction monitoring data. Results indicated an overall construction risk probability of 46.3%, with the excavation stage exhibiting the highest sensitivity index (3.97%), identifying it as the core risk control link. These findings provide a quantitative basis for dynamically identifying construction risks and optimizing mitigation measures, offering substantial practical value for enhancing safety in subway connecting passage construction within water-rich sandy strata. Full article

Background/Objectives: Vitamin D deficiency is common in the Middle East, where it affects about 90% of the population. 25-hydroxyvitamin D [25(OH)D]. plays a key role in immune function and antimicrobial defense. Its deficiency has been implicated in surgical site infections (SSIs) also, which lead to increased healthcare costs and morbidity. Around 60% SSIs are preventable by addressing factors like 25(OH)D levels among others. In Qatar, 55.8% of the population is 25(OH)D deficient, but no direct link has been established between 25(OH)D deficiency and SSI risk. This study aims to investigate the relationship between deficient 25(OH)D levels and SSI development in surgical patients at Hamad Medical Corporation (HMC), Qatar. Methods: A retrospective chart review was conducted on adult patients who underwent surgery at HMC, Qatar, between January 2021 and December 2023, with known 25(OH)D levels measured within three months before surgery. A multivariate logistic regression analysis was conducted to evaluate the relationship between 25(OH)D levels and SSIs. Results: This retrospective chart review included 24,097 patients, with 3818 (15.8%) being 25(OH)D deficient. The mean age of the patients was 45 years, and 55% of them were female. The proportion of SSIs was highest in the 25(OH)D deficient group (2.7%) compared to the insufficient (1.8%) and sufficient (1.9%) groups, with a p-value of <0.01. The mean 25(OH)D level was 23 ng/mL in the SSI group, compared to 25 ng/mL in the no SSI group, with a p-value of <0.01. Multivariate logistic regression analysis identified several independent risk factors for SSIs, including 25(OH)D deficiency, male gender, intermediate and major case levels, longer operative times, lower preoperative serum albumin, and contaminated and dirty wounds, all with p-values of <0.05. Conclusions: Preoperative lower 25(OH)D levels increase the risk of SSIs. This study emphasizes the importance of optimizing 25(OH)D levels before surgery to reduce the occurrence of SSIs. Full article

Background/Objectives: Intrathecal drug delivery is essential for treating CNS disorders, but the safety of commonly used excipients such as citric acid/sodium citrate (SC) remains unclear. This study aims to systematically evaluate the potential neuropharmacological effects of repeated intrathecal SC administration. Methods: Multimodal approaches were applied across murine and lagomorph models. Doses ranged from 1.833–14.664 μg/g in mice and 0.104–3.290 mg/rabbit. Behavioral, neurophysiological, and fiber photometry analyses were conducted to assess sensorimotor function, cortical activity, and calcium dynamics. Results: SC induced dose-dependent sensorimotor deficits, including hypolocomotion (45.7% reduced distance, p < 0.001) and impaired coordination (latency reduction 48.3–64.1%, p < 0.001). Mortality increased with dosage and repeated exposure. Neurophysiological data revealed biphasic cortical modulation: acute c-Fos suppression followed by delayed hyperactivity. Fiber photometry confirmed calcium chelation-mediated attenuation and subsequent potentiation of Ca²⁺ signals. Rabbits exhibited similar neurological symptoms, correlating with transient CSF calcium/magnesium depletion, though no structural neural damage was observed. Conclusions: These results provide the first comprehensive evidence that SC buffers can significantly disrupt neuronal calcium homeostasis and induce functional impairments upon intrathecal delivery. The findings emphasize the need for reassessing excipient safety in CNS-targeted formulations. Full article

N-lactoyl amino acids (Lac-AAs) are key players that regulate appetite and body weight. The most prominent and well-studied member is N-lactoyl phenylalanine (Lac-Phe), which can be induced by food intake, exercise and metformin treatment. However, its broader metabolic impact remains insufficiently characterized. This study investigates the effects of Lac-Phe on insulin signaling, inflammation, and mitochondrial respiration using HepG2 and differentiated C2C12 cell models, as well as isolated rat brain mitochondria and synaptosomes. Our results demonstrate that Lac-Phe significantly impairs insulin-stimulated phosphorylation of key proteins in the insulin signaling pathway, particularly in skeletal muscle cells, indicating disrupted insulin signaling. Additionally, Lac-Phe exposure increases the secretion of pro-inflammatory cytokines in C2C12 skeletal muscle cells and markedly impairs mitochondrial respiration in HepG2 liver cells and rat brain-derived synaptosomes, but not in isolated mitochondria. These findings highlight potential adverse metabolic effects of Lac-Phe, especially when administered at high concentrations, and underscore the necessity of conducting a comprehensive risk assessment and dose optimization before considering Lac-Phe or related Lac-AAs as therapeutic agents. Our work provides important insights into the molecular liabilities associated with Lac-Phe and calls for further studies to balance its therapeutic promise against possible metabolic risks. Full article

Addressing the inherent brittleness of cement to mitigate infrastructure failures stemming from cracking is imperative. To accomplish both early crack resistance and subsequent self-healing capabilities, a biomimetic microstructure composed of a sodium polyacrylate (CSPA) network interwoven with hydration products was developed. The calcium-enriched polymer network formed via in situ polymerization of sodium acrylate (ANa) can enhance the mechanical properties of cement and achieve efficient self-healing of cracks. The porous structure of sodium polyacrylate (PANa) formed in pore solution at room temperature to simulate cement hydration conditions was observed by scanning electron microscopy (SEM). Feature peaks found by Fourier transform infrared (FTIR) spectroscopy as well as confocal Raman microscopy (CRM) suggested that ANa was polymerized successfully. Notably, CSPA samples demonstrated a remarkable 104% increase in flexural strength, attributed to the efficient transmission and dissipation of external forces along the polymer network embedded within the cement matrix. Additionally, after a 28-day hydration, CSPA specimens exhibited enhanced compressive strength compared to blank cement samples. This enhancement stems from the formation of a uniform polymer network, which effectively decreased the porosity and densified the microstructure of cement. Moreover, this organic–inorganic hybrid structure contributes to efficient crack healing, as the calcium-rich polymer network binds calcium ions and promotes the generation of healing products. The healing products consist of calcium hydroxide (CH), CaCO₃ (aragonite), C-S-H (calcium–silicate–hydrate), and PANa. Full article

The junctional epithelium, which lines the inner gingival surface, seals the gingival sulcus to block the infiltration of food debris and pathogens. The junctional epithelium is derived from the reduced enamel epithelium, consisting of late developmental stage ameloblasts and accessory cells. No prior studies have investigated whether defective ameloblast differentiation or enamel matrix formation affects junctional epithelium anatomy or function. Here, we examined the junctional epithelium in mice exhibiting amelogenesis imperfecta due to loss-of-function mutations in the major enamel matrix protein amelogenin (Amelx^−/−) or the critical enamel matrix protease KLK4 (Klk4^−/−). Histological analyses demonstrated altered morphology and cell layer thickness of the junctional epithelium in Amelx^−/− and Klk4^−/− mice as compared to wt. Immunohistochemistry revealed reduced ODAM, laminin 5, and integrin α6, all of which are critical for the adhesion of the junctional epithelium to the enamel in Amelx^−/− and Klk4^−/− mice. Furthermore, we observed altered cell–cell adhesion and increased permeability of Dextran-GFP through the mutants’ junctional epithelium, indicating defective barrier function. Reduced β-catenin and Ki67 at the base of the junctional epithelium in mutants suggest impaired mitotic activity and reduced capacity to replenish continuously desquamated epithelium. These findings highlight the essential role of normal amelogenesis in maintaining junctional epithelium homeostasis. Full article

In insect–microbe symbiosis, understanding the diversity of associated bacteria is crucial. DNA-dependent sequence methods are widely used to assess microbial diversity in insects, but they cannot distinguish between live and dead microbes. In contrast, RNA-dependent sequencing can identify alive bacterial communities, making them more suitable for evaluating alive microbiota diversity. However, its practical reliability in insect–microbe symbiosis remains poorly validated. This study investigated larval gut bacteria diversity of Delia antiqua, a major pest of Liliaceae crops, by employing both DNA- and RNA-dependent 16S rRNA amplicon sequencing. The reliability of both sequencing methods was evaluated by comparing the effects of synthetic communities (SynComs, constructed according to DNA- or RNA-dependent sequencing) and bacterial communities from wild larvae on axenic larvae. Results revealed significant differences in bacterial community between DNA- and RNA-dependent sequence samples. Compared to bacterial communities from wild larvae, the SynCom constructed based on RNA-dependent sequencing exhibited inhibition effects on D. antiqua larvae survival and body weight, while DNA-dependent SynCom did not, suggesting that DNA-dependent methods were superior for assessing symbiotic microbiota in D. antiqua. This work will provide insights into microbial diversity detection in D. antiqua and offer a framework for other insect–microbe studies. Full article

Accurately estimating soil moisture (SM) without direct measurements poses significant challenges due to nonlinear interactions in meteorological variables and the lagged response of SM to precipitation. This study evaluates two approaches: the auto-regressive integrated moving average (ARIMA) model for one-day-ahead SM forecasting and a K-means clustering-based multilayer perceptron (K-MLP) for real-time SM estimation at depths of 5 cm, 20 cm, and 50 cm in Changbai Mountain region. Although the K-MLP model outperformed the MLP model, achieving a maximum R² of 0.728, its estimation accuracy remains suboptimal. By contrast, the ARIMA model effectively leveraged SM persistence, achieving high accuracy in one-day-ahead forecasting. Specifically, the ARIMA (0, 1, 6), ARIMA (1, 1, 2), and ARIMA (2, 1, 1) models yield R² values of 0.9677, 0.9853, and 0.9684 and RMSE values of 0.02 m³·m³, 0.015 m³·m³, and 0.006 m³·m³ at depths of 5 cm, 20 cm, and 50 cm, respectively. This study explores ARIMA’s robustness in short-term SM forecasting and its adaptability to dynamic meteorological conditions, offering potential applications in agricultural water management and ecological monitoring. Full article

Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. Methods: In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (w/o/w), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). Results: Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. Conclusion: The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population. Full article

Background: In recent years, the COVID-19 pandemic has significantly impacted global health, largely driven by the emergence of various genetic mutations within the SARS-CoV-2 virus. Although the pandemic phase has passed, the full extent of the virus’s evolutionary trajectory remains uncertain, highlighting the need for continued research in vaccine development to establish a cross-reactive approach that can effectively address different variants. This proof-of-concept study aimed to assess the effectiveness of microparticulate vaccine delivery through the minimally invasive microneedle route of administration, using a heterologous prime–booster strategy against the SARS-CoV-2 virus. Method: This strategy uses the whole inactivated virus of the Delta variant for the prime dose and the whole inactivated virus of the Omicron variant for the booster dose, with alum as an adjuvant. The formulation of microparticles involves encapsulating the antigens in poly lactic-co-glycolic acid (PLGA) polymer, which provides sustained release and enhances immunogenicity while protecting the antigen. Microparticles were tested for in vitro assays, and characterization included particle size, zeta potential, and encapsulation efficacy. Furthermore, serum was collected post-administration of the vaccine in mice and was tested for antibody levels. Result: In vitro assays confirmed the non-cytotoxicity and the ability of microparticles to activate the immune response of the vaccine particles. Administering this microparticulate vaccine via microneedles has proven effective for delivering vaccines through the skin. We also observed significantly higher antigen-specific antibody levels and cross-reactivity in the strains. Conclusions: Our adjuvanted microparticulate-based heterologous prime–booster vaccine strategy showed cross-reactivity among the strains and was successfully delivered using microneedles. Full article

Achieving high-precision spatiotemporal synchronization is crucial for the implementation of virtual coupling (VC) in railway systems. This paper proposes a moving baseline real-time kinematic (MB-RTK) framework to enhance relative positioning accuracy and synchronization robustness between coupled trains. By leveraging global navigation satellite system (GNSS) carrier-phase differential processing and dynamic baseline estimation, MB-RTK effectively mitigates positioning errors caused by GNSS signal degradation, multipath interference, and synchronization latency, ensuring stable and reliable inter-train coordination. The proposed framework was evaluated through comprehensive simulations and field experiments. The results demonstrate that MB-RTK achieves centimeter-level relative positioning accuracy under normal GNSS conditions, maintains tracking errors within 10 m, and typically keeps velocity synchronization deviations within ±0.5 km/h. Furthermore, the RTK status analysis reveals that NARROW_INT provides the highest stability, while continuous RTK corrections are essential to ensure seamless synchronization in dynamic environments. To further enhance synchronization performance, a decentralized distributed synchronization algorithm was introduced, reducing communication overhead and improving real-time responsiveness. The proposed approach exhibits strong resilience to GNSS disruptions, making it well-suited for high-density and autonomous train operations. Overall, this study highlights MB-RTK as a promising solution for VC applications, offering high accuracy, low latency, and strong adaptability in complex railway scenarios. Future research will focus on AI-driven dynamic corrections, integration with complementary localization methods, and large-scale deployment strategies to further optimize the system’s robustness and scalability. Full article

‘Shannongsu’ pear is a new high-quality cultivar. To ascertain the storage characteristics of ‘Shannongsu’ pears at low temperatures (0 ± 0.5 °C), the following parameters were determined: fruit firmness, ethylene, aromatic compounds, sugar content, acidity, ascorbic acid, and the expression levels of ethylene-related genes and texture-softening genes. The firmness of ‘Shannongsu’ pears changed less than that of the control, decreasing by only 18.8% after 170 days of storage. Low temperatures suppressed the expression of key genes associated with PbACS1a and PbACO1. Moreover, the expression of key genes related to fruit softening (PbPG1, PbXET, PbPME, and Pbα-L-Af) was suppressed during storage at low temperatures and remained at low levels. Therefore, the low levels of ethylene biosynthesis and the expression of key genes involved in fruit softening might play a major role in the excellent storage characteristics of the ‘Shannongsu’ cultivar. After 170 days of storage, ‘Shannongsu’ pears did not show significant changes in key quality dimensions such as firmness, sugar, acid, sugar–acid ratio, and ascorbic acid content. Therefore, low temperatures could help maintain the freshness, flavor, and nutritional quality of the ‘Shannongsu’ pear. Our findings reveal for the first time the low-temperature storage characteristics of ‘Shannongsu’ pears, providing a new scientific theoretical basis for pear production and marketing. Full article