Search Results (92)

Glycyrrhizic acid (GA) and its derivatives have been reported to have potent pharmacological effects against viral infections, including SARS-CoV and SARS-CoV-2. However, their antiviral mechanisms against coronaviruses are not fully understood. In this study, we found that diammonium glycyrrhizinate (DG) can effectively reduce infections of several human coronaviruses, including HCoV-OC43, HCoV-229E, and SARS-CoV-2, as well as newly emerged variants, with EC₅₀ values ranging from 115 to 391 μg/mL being recorded. Time-of-addition and pseudotype virus infection studies indicated that DG treatment dramatically inhibits the process of virus entry into cells. Furthermore, we demonstrated that DG broadly binds to the RBD of human coronaviruses, thereby blocking spike-mediated cellular entry, by using TR-FRET-based receptor-binding domain (RBD)-ACE2 interaction assay, capillary electrophoresis (CE), and surface plasmon resonance (SPR) assay. In support of this notion, studies of molecular docking and amino acid mutation showed that DG may directly bind to a conserved hydrophobic pocket of the RBD of coronaviruses. Importantly, intranasal administration of DG had a significant protective effect against viral infection in a HCoV-OC43 mouse model. Finally, we found that combinations of DG and other coronavirus inhibitors exhibited antiviral synergy. In summary, our studies strongly reveal that DG exerts broad-spectrum antiviral activity against human coronaviruses by interrupting spike-mediated cellular entry, demonstrating the pharmacological feasibility of using DG as a candidate for alternative treatment and prevention of coronavirus infection. Full article

Dragon fruit comprises a wide variety of species that are rich in nutritional value and have great economic potential; however, numerous studies have focused on their nutritional and commercial quality. In contrast, few studies have addressed their flavor quality, particularly with respect to the regulatory networks responsible for their flavor-related substance contents. To this end, we sequenced the transcriptomes and metabolomes of red-skin/white-fleshed and red-skin/red-fleshed dragon fruit at different timepoints during fruit development. RNA-seq and metabolome data were used to divide the seven developmental stages of the dragon fruit into four categories (young fruit, expansion, maturity, and senescence). In all, 16,827 differentially expressed genes (DEGs), including 958 transcription factors, were identified and grouped into 10 clusters, and the pathways in each cluster were annotated. Additionally, 318 differentially accumulated metabolites (DAMs) were identified, including 88 common metabolites. The main flavor-related substances and the key genes regulating them were determined via joint analysis via RNA-seq and metabolomics. Furthermore, 10 volatile active components related to green flavors and aromas were screened according to the relative odor activity value (ROAV), and 15 candidate genes related to key flavor compounds were screened via WGCNA, 3 of which encoded transcription factors. In conclusion, our results provide a theoretical basis for an in-depth understanding of the volatile flavor compounds in dragon fruit and provide new genetic resources for the subsequent study of fruit flavor compounds. Full article

In laser-directed energy deposition (LDED) additive manufacturing, stress-induced deformation and cracking often occur unexpectedly, and, once initiated, they are difficult to remedy. To address this issue, we previously proposed the Dynamic Counter Method (DCM), which monitors internal stress based on deposition layer shrinkage, enabling real-time stress monitoring without damaging the component. To validate this method, we used AlSi10Mg material, which has a low melting point and high reflectivity, and developed a high-precision segmentation network based on DeeplabV3+ to test its ability to measure shrinkage in high-exposure images. Using a real-time reconstruction model, stress calculations were performed with DCM and thermal–mechanical coupling simulations, and the results were validated through XRD residual stress testing to confirm DCM’s accuracy in calculating internal stress in aluminum alloys. The results show that the DeeplabV3+ segmentation network accurately extracted deposition-layer contours and shrinkage information. Furthermore, DCM and thermal–mechanical coupling simulations showed good consistency in residual stress distribution, with all results falling within the experimental error range. In terms of stress evolution trends, DCM was also effective in predicting stress variations. Based on these findings, two loading strategies were proposed, and, for the first time, DCM’s application in online stress monitoring of large LDED components was validated, offering potential solutions for stress monitoring in large-scale assemblies. Full article

Primary angle-closure glaucoma (PACG), characterized by angle closure (AC) with insidious and irreversible progression, requires precise assessment of AC mechanisms for accurate diagnosis and treatment. This study developed an artificial intelligence system, ACM-Assessor, to evaluate AC mechanisms in ultrasound biomicroscopy (UBM) images. A dataset of 8482 UBM images from 1160 patients was retrospectively collected. ACM-Assessor comprises models for pixel-to-physical spacing conversion, anterior chamber angle boundary segmentation, and scleral spur localization, along with three binary classification models to assess pupillary block (PB), thick peripheral iris (TPI), and anteriorly located ciliary body (ALCB). The integrated assessment model classifies AC mechanisms into pure PB, pure non-PB, multiple mechanisms (MM), and others. ACM-Assessor’s evaluation encompassed external testing (2266 images), human–machine competition and assisting beginners’ assessment (an independent test set of 436 images). ACM-Assessor achieved accuracies of 0.924 (PB), 0.925 (TPI), 0.947 (ALCB), and 0.839 (integrated assessment). In man–machine comparisons, the system’s accuracy was comparable to experts (p > 0.05). With model assistance, beginners’ accuracy improved by 0.117 for binary classification and 0.219 for integrated assessment. ACM-Assessor demonstrates expert-level accuracy and enhances beginners’ learning in UBM analysis. Full article

Apron is a commonly used structure in the downstream of debris-flow-retaining dams. Its function is to resist the impact and erosion of debris flow on the dam foundation. In order to enhance the impact resistance of the apron to boulders, increasing the apron thickness and filling the block stone are usually adopted. However, the apron is still often destroyed by bouldery debris flow. Therefore, we propose a kind of toughness apron. Physical test and numerical simulation are used to reveal the dynamic response of the toughness apron. The results show that both tire cushion and stone cushion can buffer the impact of boulders. The physical test showed that the cushion reduces impact force and vibration acceleration, and the numerical simulation results indicate that the cushion significantly reduces damage to the protection apron while dissipating most of the energy. It was also found that there is an energy threshold of impact damage resistance of the apron. When the impact kinetic energy is higher than this threshold, the apron will be damaged. These findings highlight its potential for debris flow protection. According to the corresponding impact characteristics of the dam, the design method of the toughness apron is proposed. Full article

This study optimized the process of extracting protein from black garlic using an alkaline dissolution and acid precipitation method through response surface methodology. The optimal extraction conditions were determined as a solid-to-liquid ratio of 1:50, an extraction time of 100 min, an extraction temperature of 30 °C, and an alkaline extraction pH of 9.0. Under these optimized conditions, the actual black garlic protein (BGP) extraction yield was 12.10% ± 0.21%, and the isoelectric point of the obtained BGP was 3.1. Subsequently, this study extracted black garlic protein under optimal conditions and subjected it to enzymatic hydrolysis using different enzymes (trypsin, pepsin, and their mixed enzymes). The functional characteristics, antioxidant activity, and hypoglycemic activity of black garlic protein before and after enzymatic hydrolysis were compared. Among the hydrolysates, the pepsin hydrolysate (BGPH-P) had the smallest particle size (188.57 ± 1.93 nm) and the highest Zeta potential (−29.93 ± 0.42 mV). Scanning electron microscopy showed that BGPH-P had the smallest and most dispersed particles. Fourier-transform infrared (FTIR) spectroscopy revealed that the dual enzymatic hydrolysis hydrolysate (BGPH-PT) exhibited the most stable structure. Compared to BGP, the hydrolysates demonstrated significantly improved solubility, water-holding capacity, and foaming ability (p < 0.05), while their emulsifying activity, emulsion stability, DPPH radical scavenging capacity, and hypoglycemic activity decreased. In summary, the BGP extracted using the optimized process demonstrated good antioxidant and hypoglycemic activities, while its enzymatic hydrolysate BGPH-P exhibited excellent solubility, water-holding capacity, and emulsifying properties, providing valuable insights for the further development of black garlic protein and its hydrolysates. Full article

An 8-week feeding trial was conducted to evaluate the effects of dietary fermented rapeseed meal (FRM), potassium iodide, and their interactions on growth performance, approximate composition, and antioxidant capacity in tilapia, Oreochromis niloticus (initial body weight: 3.50 ± 0.15 g). Six isonitrogenous and isolipidic diets from a 2 × 3 factorial design were formulated with two levels of FRM (25.8 and 51.6%) and three levels of potassium iodide (0, 6, and 12 mg/kg), respectively. The results indicated that dietary levels of FRM and iodine had no significant influence on the SR of tilapia but exerted significant effects on weight gain (WG), specific growth rate (SGR), feed intake (FI), hepatosomatic index, and viscerosomatic index. The WG, SGR, and FI of tilapia in the 51.6% FRM groups were significantly lower than those in other groups (p < 0.05), and iodine inclusion in the 51.6% FRM diet significantly enhanced WG, SGR, and FI of tilapia (p < 0.05). Dietary iodine significantly increased the whole-body and muscle lipid content in the tilapia (p < 0.05). The content of total bilirubin (T-Bil) and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the tilapia serum were significantly reduced by the inclusion of 6–12 mg/kg iodine in 51.6% FRM level (p < 0.05), and the serum total triiodothyronine content was significantly elevated by the supplementation of 12 mg/kg iodine (p < 0.05). Significant interactions between dietary FRM and iodine were found in serum T-Bil content and triglyceride and AST activity (p < 0.05). Dietary supplementation of iodine in high FRM diets (51.6%) significantly increased the activities of total superoxide dismutase (T-SOD), catalase (CAT), and total antioxidant capacity (T-AOC) and decreased the content of malondialdehyde (MDA) in the liver of tilapia (p < 0.05). The activity of T-SOD, CAT, and T-AOC and the content of MDA in the liver of tilapia significantly interacted with the levels of dietary FRM and iodine (p < 0.05). Furthermore, the liver cell structure was further ameliorated, and the liver health status was significantly enhanced in each iodine treatment group. Full article

Milk is one of the most common sources of nutrients in humans, however, the composition and healthy value of the milk derived from different animals are very different. Here, we systemically compared the protein and lipid profiles and evaluated the anti-inflammation and antioxidant effect of buffalo and Holstein-derived milk on Caco-2 cells. Results showed that 906 proteins and 1899 lipids were identified in the buffalo milk and Holstein milk samples including 161 significantly different proteins (DEPs) and 49 significantly different lipids. The DEPs were mainly enriched in defense response-related terms, while the differential lipids were mainly included in fat digestion and absorption and cholesterol metabolism pathways. In addition, the Caco-2 cells co-cultured with buffalo and Holstein milk components showed significant benefits in being resistant to LPS-induced inflammation stress and H₂O₂-induced ROS stress. The qRT-PCR and ELISA results showed that the expression of TNF-α, IL-1β, and IL-6 was significantly lower (p < 0.05) in the cells co-cultured with milk components. Further analysis showed that, after H₂O₂ treatment, the expression of keap1 and Nrf-2 in the Caco-2 cells co-cultured with milk components was significantly lower (p < 0.05). In addition, being co-cultured with milk components significantly decreased the SOD, MDA, CAT, and GSH-Px content (p < 0.05) in the Caco-2 cells induced by H₂O₂. This study provides a novel insight into the differences in proteins and lipids between buffalo milk and Holstein milk, and a reference understanding of the anti-inflammation and antioxidant effect of the consumption of milk on the intestines. Full article

This study aimed to provide foundational research for the biological control of postharvest avocado fruits anthracnose and establish a microbial system of postharvest avocado fruits. The high-throughput sequencing of avocado fruits from the anthracnose-infected and healthy groups was performed using Illumina NovaSeq second-generation sequencing technology. The results revealed that, except for Colletotrichum sp. strain 38#, there were differences in the bacterial community structure of avocados before and after infection, as determined through alpha and beta diversity analysis. Additionally, there were significant differences in the endophytic fungal community structure, allowing clear differentiation between the infected and healthy avocados. The endophytic bacterial community was primarily composed of 4 phyla and 10 genera, with the Bacteroidota phylum and Chryseobacterium genus demonstrating sensitivity to anthracnose pathogens, as evidenced by a decrease in their relative abundance after infection. The endophytic fungal community was characterized by 3 phyla and 10 genera. After infection, the relative abundance of 2 phyla (Anthophyta and Basidiomycota) and 7 genera (Eucalyptus, Candida, Kluyveromyces, Talaromyces, Oidiodendron, Nigrospora, and Pestalotiopsis) decreased, whereas the relative abundance of the Colletotrichum genus increased dramatically. The LEfSe (Linear discriminant analysis Effect Size) analysis indicated that significant biomarkers were more prevalent in endophytic bacteria than in endophytic fungi in the avocados. In endophytic bacteria, the key biomarkers included the Firmicutes phylum (Bacilli class), Proteobacteria phylum (Gammaproteobacteria class, Pseudomonadales order, Pseudomonadaceae family, and Pseudomonas genus), Flavobacteriales order, Weeksellaceae family, and Chryseobacterium genus. In endophytic fungi, the important biomarkers were Saccharomycetes class (Saccharomycetales order), Glomerellales order (Glomerellaceae family and Colletotrichum genus), and Botryosphaeriales order (Botryosphaeriaceae family and Lasiodiplodia genus). These results may provide a theoretical basis for the development of future biological agents for avocado anthracnose. Full article

Background: As an ancient concept and practice, “food as medicine” or “medicine–food homology” is receiving more and more attention these days. It is a tradition in many regions to intake medicinal herbal food for potential health benefits to various organs and systems including the kidney. Kidney diseases usually lack targeted therapy and face irreversible loss of function, leading to dialysis dependence. As the most important organ for endogenous metabolite and exogenous nutrient excretion, the status of the kidney could be closely related to daily diet. Therefore, medicinal herbal food rich in antioxidative, anti-inflammation micronutrients are ideal supplements for kidney protection. Recent studies have also discovered its impact on the “gut–kidney” axis. Methods: Here, we review and highlight the kidney-protective effects of botanicals with medicine–food homology including the most frequently used Astragalus membranaceus and Angelica sinensis (Oliv.) Diels, concerning their micronutrients and mechanism, offering a basis and perspective for utilizing and exploring the key substances in medicinal herbal food to protect the kidney. Results: The index for medicine–food homology in China contains mostly botanicals while many of them are also consumed by people in other regions. Micronutrients including flavonoids, polysaccharides and others present powerful activities towards renal diseases. Conclusions: Botanicals with medicine–food homology are widely speeded over multiple regions and incorporating these natural compounds into dietary habits or as supplements shows promising future for renal health. Full article

The liver plays an important role in regulating lipid metabolism in animals. This study investigated the function and mechanism of lncLLM in liver lipid metabolism in hens at the peak of egg production. The effect of lncLLM on intracellular lipid content in LMH cells was evaluated by qPCR, Oil Red O staining, and detection of triglyceride (TG) and cholesterol (TC) content. The interaction between lncLLM and MYH9 was confirmed by RNA purification chromatin fractionation (CHIRP) and RNA immunoprecipitation (RIP) analysis. The results showed that lncLLM increased the intracellular content of TG and TC and promoted the expression of genes related to lipid synthesis. It was further found that lncLLM had a negative regulatory effect on the expression level of MYH9 protein in LMH cells. The intracellular TG and TC content of MYH9 knockdown cells increased, and the expression of genes related to lipid decomposition was significantly reduced. In addition, this study confirmed that the role of lncLLM is at least partly through mediating the ubiquitination of MYH9 protein to accelerate the degradation of MYH9 protein. This discovery provides a new molecular target for improving egg-laying performance in hens and treating fatty liver disease in humans. Full article

Acetylation modification has become one of the most popular topics in protein post-translational modification (PTM) research and plays an important role in bacterial virulence. A previous study indicated that the virulence-associated caseinolytic protease proteolytic subunit (ClpP) is acetylated at the K165 site in Vibrio alginolyticus strain HY9901, but its regulation regarding the virulence of V. alginolyticus is still unknown. We further confirmed that ClpP undergoes lysine acetylation (Kace) modification by immunoprecipitation and Western blot analysis and constructed the complementation strain (C-clpP) and site-directed mutagenesis strains including K165Q and K165R. The K165R strain significantly increased biofilm formation at 36 h of incubation, and K165Q significantly decreased biofilm formation at 24 h of incubation. However, the acetylation modification of ClpP did not affect the extracellular protease (ECPase) activity. In addition, we found that the virulence of K165Q was significantly reduced in zebrafish by in vivo injection. To further study the effect of lysine acetylation on the pathogenicity of V. alginolyticus, GS cells were infected with four strains, namely HY9901, C-clpP, K165Q and K165R. This indicated that the effect of the K165Q strain on cytotoxicity was significantly reduced compared with the wild-type strain, while K165R showed similar levels to the wild-type strain. In summary, the results of this study indicate that the Kace of ClpP is involved in the regulation of the virulence of V. alginolyticus. Full article

Autonomous driving technology has advanced significantly with deep learning, but noise and attacks threaten its real-world deployment. While research has revealed vulnerabilities in individual intelligent tasks, a comprehensive evaluation of these impacts across complete end-to-end systems is still underexplored. To address this void, we thoroughly analyze the robustness of four end-to-end autonomous driving systems against various noise and build the RobustE2E Benchmark, including five traditional adversarial attacks and a newly proposed Module-Wise Attack specifically targeting end-to-end autonomous driving in white-box settings, as well as four major categories of natural corruptions (a total of 17 types, with five severity levels) in black-box settings. Additionally, we extend the robustness evaluation from the open-loop model level to the closed-loop case studies of autonomous driving system level. Our comprehensive evaluation and analysis provide valuable insights into the robustness of end-to-end autonomous driving, which may offer potential guidance for targeted improvements to models. For example, (1) even the most advanced end-to-end models suffer large planning failures under minor perturbations, with perception tasks showing the most substantial decline; (2) among adversarial attacks, our Module-Wise Attack poses the greatest threat to end-to-end autonomous driving models, while PGD-$l2$ is the weakest, and among four categories of natural corruptions, noise and weather are the most harmful, followed by blur and digital distortion being less severe; (3) the integrated, multitask approach results in significantly higher robustness and reliability compared with the simpler design, highlighting the critical role of collaborative multitask in autonomous driving; and (4) the autonomous driving systems amplify the model’s lack of robustness, etc. Our research contributes to developing more resilient autonomous driving models and their deployment in the real world. Full article

Addressing the challenge of radar detection of small targets under sea clutter, target detection methods based on a three-dimensional feature space have shown effectiveness. However, their application has revealed several problems, including high dependency on linear relationships between features for dimensionality reduction, unclear reduction objectives, and spatial divergence of target samples, which limit detection performance. To mitigate these challenges, we constructed a feature density distance metric employing copula functions to quantitatively describe the classification capability of multidimensional features to distinguish targets from sea clutter. On the basis of this, a lightweight nonlinear dimensionality reduction network utilizing a self-attention mechanism was developed, optimally re-expressing multidimensional features into a three-dimensional feature space. Additionally, a concave hull classifier using feature sample distance was proposed to mitigate the negative impact of target sample divergence in the feature space. Furthermore, multivariate autoregressive prediction was used to optimize features, reducing erroneous decisions caused by anomalous feature samples. Experimental results using the measured data from the SDRDSP public dataset demonstrated that the proposed detection method achieved a detection probability more than 4% higher than comparative methods under Sea State 5, was less affected by false alarm rates, and exhibited superior detection performance under different false alarm probabilities from 10⁻³ to 10⁻¹. Full article

Salinization of freshwater ecosystems is a pressing global issue. Changes in salinity can exert severe pressure on aquatic animals and jeopardize their survival. Procambarus clarkii is a valuable freshwater aquaculture species that exhibits some degree of salinity tolerance, making it an excellent research model for freshwater aquaculture species facing salinity stress. In the present study, crayfish were exposed to acute low salt (6 ppt) and high salt (18 ppt) conditions. The organisms were continuously monitored at 6, 24, and 72 h using RNA-Seq to investigate the mechanisms of salt stress resistance. Transcriptome analysis revealed that the crayfish responded to salinity stress with numerous differentially expressed genes, and most of different expression genes was observed in high salinity group for 24h. GO and KEGG enrichment analyses indicated that metabolic pathways were the primary response pathways in crayfish under salinity stress. This suggests that crayfish may use metabolic pathways to compensate for energy loss caused by osmotic stress. Furthermore, gene expression analysis revealed the differential expression of immune and antioxidant-related pathway genes under salinity stress, implying that salinity stress induces immune disorders in crayfish. More genes related to cell proliferation, differentiation, and apoptosis, such as the Foxo, Wnt, Hippo, and Notch signaling pathways, responded to high-salinity stress. This suggests that regulating the cellular replication cycle and accelerating apoptosis may be necessary for crayfish to cope with high-salinity stress. Additionally, we identified 36 solute carrier family (SLC) genes related to ion transport, depicting possible ion exchange mechanisms in crayfish under salinity stress. These findings aimed to establish a foundation for understanding crustacean responses to salinity stress and their osmoregulatory mechanisms. Full article