Search

Background: Pulmonary infections resulting from respiratory syncytial virus (RSV) continue to pose a significant threat to the well-being of infants and the elderly, but there is no safe, effective and specific treatment except symptomatic treatment. Forsythia Suspensa Leaf (FSL) is cold in nature and bitter in taste, and has the efficacy of clearing away heat and toxic materials. Previous research by our research group showed that the active components in FSL have the pharmacological effect of anti-RSV. Based on that, this study aims further to clarify the anti-RSV active components and mechanism of FSL. Methods: Firstly, we established the BALB/c mouse model of RSV infection, assessed the in vivo anti-RSV efficacy, and determined the optimal dosage of FSL and its active components. Evaluation parameters included body weight changes, organ indices, lung tissue pathological sections, lung tissue viral load, and inflammatory factors. Additionally, we used RT-PCR, Western Blot and other molecular biology techniques to determine the expression changes of key factors such as Nrf2 and NLRP3 in PI3K/Akt-NLRP3 pathway, and revealed the anti-RSV mechanism of FSL and its active components. Results: Pharmacodynamic experiments in animals showed that the FSL Low (0.4 g/kg·d), RosA Low (100 mg/kg·d) and Phillyrin Medium (100 mg/kg·d) groups could effectively improve the pathological conditions of mice with RSV pneumonia, such as weight loss, the level of pulmonary inflammatory factors and the increase of viral load. In addition, oral administration of Phillyrin at a dose of 100 mg/kg d to RSV-infected mice can effectively control the trend that the expression of Nrf2 protein decreases and the expression of NLRP3 protein increases in RSV pneumonia mice. Conclusion: Phillyrin, the active component in FSL, can not only directly inhibit the replication of RSV, but also effectively control the inflammatory reaction caused by RSV infection and improve lung injury, which is expected to become a potential drug against RSV pneumonia.

BackgroundAsthma is a chronic respiratory condition affecting populations worldwide, with prevalence ranging from 1–18% across different nations. Gender differences in asthma prevalence have attracted much attention.PurposeThe aim of this study was to investigate biomarkers of gender differences in asthma prevalence based on machine learning.MethodThe data came from the gene expression omnibus database (GSE69683, GSE76262, and GSE41863), which involved in a number of 575 individuals, including 240 males and 335 females. Theses samples were divided into male group and female group, respectively. Grid search and cross-validation were employed to adjust model parameters for support vector machine, random forest, decision tree and logistic regression model. Accuracy, precision, recall, and F1 score were used to evaluate the performance of the models during the training process. After model optimization, four machine learning models were utilized to predict biomarkers of sex differences in asthma. In order to validate the accuracy of our results, we performed Wilcoxon tests on the genes expression.ResultIn datasets GSE76262 and GSE69683, support vector machine, random forest, logistic regression, and decision tree all achieve 100% accuracy, precision, recall, and F1 score. Our findings reveal that XIST serves as a common biomarker among the three samples, comprising a total of 575 individuals, with higher expression levels in females compared to males (p

Artificial optoelectronic synaptic transistors have attracted extensive research interest as an essential component for neuromorphic computing systems and brain emulation applications. However, performance challenges still remain for synaptic devices, including low energy consumption, high integration density, and flexible modulation. Employing trapping and detrapping relaxation, a novel optically stimulated synaptic transistor enabled by the AlGaN/GaN hetero-structure metal-oxide semiconductor high-electron-mobility transistor has been successfully demonstrated in this study. Synaptic functions, including excitatory postsynaptic current (EPSC), paired-pulse facilitation index, and transition from short-term memory to long-term memory, are well mimicked and explicitly investigated. In a single EPSC event, the AlGaN/GaN synaptic transistor shows the characteristics of low energy consumption and a high signal-to-noise ratio. The EPSC of the synaptic transistor can be synergistically modulated by both optical stimulation and gate/drain bias. Moreover, utilizing a convolution neural network, hand-written digit images were used to verify the data preprocessing capability for neuromorphic computing applications.

Abstract Background Respiratory Syncytial Virus (RSV) stands out as a primary contributor to lower respiratory tract infections and hospitalizations, particularly in infants. Lonicerae japonicae flos (LJF), a traditional Chinese medicine renowned for its efficacy against various viral infections, including RSV, has been widely employed. Despite its common use, the precise therapeutic mechanism of LJF against RSV remains elusive. This study aimed to investigate the underlying mechanism of LJF against RSV through network pharmacology and metabolomics. Methods In this study, based on network pharmacology, potential targets related to LJF and RSV were obtained from PubChem and Swiss Target Prediction. The core targets and pathways were established and verified by enrichment analysis and molecular docking. The anti-RSV efficacy of LJF was determined by in vitro experiments. Additionally, metabolomics analysis was integrated, allowing for the identification of differential metabolites and their correlation with targets following LJF treatment in the context of RSV infection. Results A total of 23 active ingredients and 780 targets were obtained, of which 102 targets were associated with LJF anti-RSV. The construction of the corresponding Protein–Protein Interaction (PPI) network unveiled potential core targets, including STAT3, TNF, and AKT1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that LJF's anti-RSV effects primarily involve key pathways such as the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and FoxO signaling pathway. Molecular docking showed that ZINC03978781, 4,5'-Retro-.beta.,.beta.-Carotene -3,3'-dione, 4',5'-didehydro and 7-epi-Vogeloside had better binding ability. The cellular assay showed that the therapeutic index of LJF against RSV was 4.79. Furthermore, 18 metabolites were screened as potential biomarkers of LJF against RSV, and these metabolites were mainly involved in the pathways of purine metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and other related pathways. Conclusions The intergration of network pharmacology and metabolomics can clarify the active targets and related pathways of LJF against RSV, which could provide a valuable reference for further research and clinical application of LJF.

Many metabolic diseases have been demonstrated to be associated with changes in the microbiome. However, no studies have yet been conducted to examine the characteristics of the mucosal microbiota of patients with hypercholesterolemia. We aimed to examine mucosa-associated microbiota in subjects with hypercholesterolemia. We conducted a case-control study, in which ileal mucosal samples were collected from 13 hypercholesterolemia patients and 13 controls for 16S rRNA gene sequencing. There were differences in the composition of ileal mucosal microbiota based on beta diversity between the hypercholesterolemia and control groups (P

The mechanical-double enzyme method was used in the current study to isolate and culture primary chondrocytes from the chicken growth plates. The feasibility and practicability of the approach were determined by using trypan blue staining, toluidine blue staining, PCR, and flow cytometry. The immunofluorescence assay was also used to effectively identify chondrocytes, demonstrating the expression of chondrocyte-specific secreted products (Col-II and Aggrecan). The exterior morphology of chondrocytes was studied at several stages, revealing significant changes in cell shape with each generation. Notably, compared to earlier approaches, the mechanical-double enzyme strategy revealed enhanced cell adhesion and much reduced apoptosis rates. The findings indicate that this novel method has great potential for efficient primary chondrocytes culture, providing important insight into chondrocyte ba research and future applications in cartilage tissue engineering.The following technical points are included in this method: • Isolation and culturing primary chondrocytes by a mechanical-double enzyme approach. • The evaluation of cell adhesion and apoptosis of mechanical double enzyme approach as compared to previous approaches. • The confirmation of chondrocyte-specific secreted products' expression via toluidine blue staining, PCR, and immunofluorescence assays.

Black Phosphorus (BP) is a new semiconductor material with excellent biocompatibility, degradability, and optical and electrophysical properties. A growing number of studies show that BP has high potential applications in the biomedical field. This article aims to systematically review the research progress of BP composite medical materials in the field of tissue engineering, mining BP in bone regeneration, skin repair, nerve repair, inflammation, treatment methods, and the application mechanism. Furthermore, the paper discusses the shortcomings and future recommendations related to the development of BP. These shortcomings include stability, photothermal conversion capacity, preparation process, and other related issues. However, despite these challenges, the utilization of BP-based medical materials holds immense promise in revolutionizing the field of tissue repair.

BackgroundDue to environmental pollution, changes in lifestyle, and advancements in diagnostic technology, the prevalence of asthma has been increasing over the years. Although China has made early efforts in asthma epidemiology and prevention, there is still a lack of unified and comprehensive epidemiological research within the country. The objective of the study is to determine the nationwide prevalence distribution of asthma using the Baidu Index and China's Health Statistical Yearbook.MethodsBased on China's Health Statistical Yearbook, we analyzed the gender and age distribution of asthma in China from 2011 to 2020, as well as the length of hospitalization and associated costs. By utilizing the Baidu Index and setting the covering all 31 provinces and autonomous regions in China, we obtained the Baidu Index for the keyword 'asthma'. Heatmaps and growth ratios described the prevalence and growth of asthma in mainland China.ResultsThe average expenditure for discharged asthma (standard deviation) patients was ¥5,870 (808). The average length of stay (standard deviation) was 7.9 (0.38) days. During the period of 2011 to 2020, hospitalization expenses for asthma increased while the length of hospital stay decreased. The proportion of discharged patients who were children under the age of 5 were 25.3% (2011), 19.4% (2012), 16% (2013), 17.9% (2014), 13.9% (2015), 11.3% (2016), 10.2% (2017), 9.4% (2018), 8.1% (2019), and 7.2% (2020), respectively. The prevalence of asthma among boys was higher than girls before the age of 14. In contrast, the proportion of women with asthma was larger than men after the age of 14. During the period from 2011 to 2020, the median [The first quartile (Q1)-the third quartile (Q3)] daily asthma Baidu index in Guangdong, Beijing, Jiangsu, Sichuan, and Zhejiang were 419 (279–476), 328 (258–376), 315 (227–365), 272 (166–313), and 312 (233–362) respectively. Coastal regions showed higher levels of attention toward asthma, indicating a higher incidence rate. Since 2014, there has been a rapid increase in the level of attention toward asthma, with the provinces of Qinghai, Sichuan, and Guangdong experiencing the fastest growth.ConclusionThere are regional variations in the prevalence of asthma among different provinces in China, and the overall prevalence of asthma is increasing.

The aim of this study is to identify an alternative approach for simulating the in vitro fermentation and quantifying the production of rumen methane and rumen acetic acid during the rumen fermentation process with different total mixed rations. In this experiment, dietary nutrient compositions (neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), and dry matter (DM)) were selected as input parameters to establish three prediction models for rumen fermentation parameters (methane and acetic acid): an artificial neural network model, a genetic algorithm-bp model, and a support vector machine model. The research findings show that the three models had similar simulation results that aligned with the measured data trends (R2 ≥ 0.83). Additionally, the root mean square errors (RMSEs) were ≤1.85 mL/g in the rumen methane model and ≤2.248 mmol/L in the rumen acetic acid model. Finally, this study also demonstrates the models’ capacity for generalization through an independent verification experiment, as they effectively predicted outcomes even when significant trial factors were manipulated. These results suggest that machine learning-based in vitro rumen models can serve as a valuable tool for quantifying rumen fermentation parameters, guiding the optimization of dietary structures for dairy cows, rapidly screening methane-reducing feed options, and enhancing feeding efficiency.

Abstract The switched‐capacitor DC‐DC converters have been widely applied to convert energy from low voltage to DC bus for the power generation systems with fuel cells, photovoltaic array, and so on. However, the large capacitance is generally selected to eliminate the high current spike of switched‐capacitors in the hard‐switching switched‐capacitor (SC) DC‐DC converters, which will lead to the large volume and weight of capacitors and of converters. To solve this problem, a non‐resonant soft‐switching (NRSS) technique with linear current on switching cycle time‐scale for switched‐capacitor DC‐DC converters is first proposed in this paper, which achieves zero‐current‐switching (ZCS) turn‐on of switches and ZCS turn‐off of diodes with linear current on switching cycle time‐scale. In detail, the NRSS technique is proposed based on the idea that the current of an auxiliary inductor on switching cycle time‐scale is considered as the linear parts for the resonant current of the auxiliary inductor on resonant cycle time‐scale. The proposed NRSS technique is utilized into SC DC‐DC converter and the current spikes of switches can be reduced to two third by using the same capacitance compared with the hard‐switching SC DC‐DC converters and be reduced to a third compared with the resonant soft‐switching SC DC‐DC converters. Further, nine new soft‐switching SC DC‐DC converters, with single switch and double switches, are built based on the proposed non‐resonant soft‐switching technique. Finally, the non‐resonant soft‐switching technique is verified theoretically and experimentally by three of the nine proposed SC DC‐DC converters. This paper provides a new way to realize soft‐switching during the non‐resonant interval on switching cycle time‐scale and a new method to significantly reduce the required capacitance in SC DC‐DC converters.

There is evidence to suggest that microRNA-140-5p (miR-140), which acts as a suppressor, is often elevated and has a role in various malignancies. Nevertheless, neither the function nor the mechanisms in chondrocytes linked with bone disorders, e.g., tibial dyschondroplasia (TD), have been satisfactorily established. The purpose of this study was to look into the role of microRNA-140-5p (miR-140) and its interaction with HDAC4 in chondrocytes, as well as the implications for tibial dyschondroplasia (TD), with a particular focus on the relationship between low miR-140 expression and poor pathologic characteristics, as well as its physiological effects on chondrocyte growth, differentiation, and chondrodysplasia. In this investigation, we discovered that TD had a reduced expression level of the miR-140. There was a correlation between low miR-140 expression, poor pathologic characteristics, and the short overall survival of chondrocytes. Our findings show an aberrant reduction in miR-140 expression, and HDAC4 overexpression caused disengagement in resting and proliferation zones. This further resulted in uncontrolled cell proliferation, differentiation, and chondrodysplasia. Mechanistically, HDAC4 inhibited the downstream transcription factors MEF2C and Runx2 and interacted with Col-Ⅱ, Col-X, and COMP. However, miR-140 binding to the 3′-UTR of HDAC4 resulted in the growth and differentiation of chondrocytes. Moreover, the expression of HDAC4 through LMK-235 was significantly decreased, and the expression was significantly increased under ITSA-1, referring to a positive feedback circuit of miR-140 and HDAC4 for endochondral bone ossification. Furthermore, as a prospective treatment, the flavonoids of Rhizoma drynariae (TFRD) therapy increased the expression of miR-140. Compared to the TD group, TFRD treatment increased the expression of growth-promoting and chondrocyte differentiation markers, implying that TFRD can promote chondrocyte proliferation and differentiation in the tibial growth plate. Hence, directing this circuit may represent a promising target for chondrocyte-related bone disorders and all associated pathological bone conditions.

Satellite–ground integrated networks (SGIN) are in line with 6th generation wireless network technology (6G) requirements. However, security and privacy issues are challenging with heterogeneous networks. Specifically, although 5G authentication and key agreement (AKA) protects terminal anonymity, privacy preserving authentication protocols are still important in satellite networks. Meanwhile, 6G will have a large number of nodes with low energy consumption. The balance between security and performance needs to be investigated. Furthermore, 6G networks will likely belong to different operators. How to optimize the repeated authentication during roaming between different networks is also a key issue. To address these challenges, on-demand anonymous access and novel roaming authentication protocols are presented in this paper. Ordinary nodes implement unlinkable authentication by adopting a bilinear pairing-based short group signature algorithm. When low-energy nodes achieve fast authentication by utilizing the proposed lightweight batch authentication protocol, which can protect malicious nodes from DoS attacks. An efficient cross-domain roaming authentication protocol, which allows terminals to quickly connect to different operator networks, is designed to reduce the authentication delay. The security of our scheme is verified through formal and informal security analysis. Finally, the performance analysis results show that our scheme is feasible.

Abstract Background The aim was to determine the potential association of the gut microbiota composition, especially the abundance of Actinobacteria, as well as the differentiation of functional and resistance genes with age (young adults vs elderly subjects) in China. Results The patterns of relative abundance of all bacteria isolated from fecal samples differed between young adults and elderly subjects, but the alpha diversity (Chao1 P = 0.370, Shannon P = 0.560 and Simpson P = 0.270) and beta diversity (ANOSIM R = 0.031, P = 0.226) were not significantly different. There were 3 Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways (carbon metabolism, inositol phosphate metabolism, and sesquiterpenoid and triterpenoid biosynthesis) and 7 antibiotic resistant genes (ARGs) (macrolide lincosamide-streptogramin B (MLSB), tetracycline, aminoglycoside, sulfonamide, fosmidomycin, lincomycin, and vancomycin) that showed significant differences between the 2 groups (all P 0.05). Only the Bifidobacterium_dentium species showed significant differences between the 2 groups (P = 0.013), with a higher abundance in elderly subjects but absent in young adults. Conclusions The present study revealed that there were 3 KEGG metabolic pathways and 7 ARGs as well as enhanced Bifidobacterium_dentium species abundance in elderly compared to young subjects.

ABSTRACT Bacillus amyloliquefaciens is a nonpathogenic microorganism whose highly active amylase is widely isolated from soil and plants. TL106 is an isolate of Bacillus amyloliquefaciens isolated from cold- and disease-resistant Tibetan pigs in Linzhi, Tibet. Here, we report that TL106 not only could survive in acidic environments, high bile salt concentrations, and high-temperature conditions but also was resistant to antibiotics. It significantly improved the growth performance of weaned piglets, especially in the prevention of diarrhea. The crude fiber and crude ash digestibility in weaned piglets after TL106 administration was considerably higher than that in other groups. The results of 16S rRNA sequencing conveyed that TL106 stabilized gut microbiota that was disturbed by the weaning process with an increased level of Lachnospiraceae, Peptococcaceae.rc4_4, Erysipelotrichaceae.L7A_E11, and Mollicutes.RF39. Hence, this study proved that Bacillus amyloliquefaciens TL106 might be a candidate for antibiotics in Duroc×Landrace×Yorkshire weaned piglets. IMPORTANCE Antibiotics are often used to promote animal growth and prevent diarrhea in weanling piglets. Nevertheless, intestinal pathogenic bacterial resistance and drug residues caused by antibiotic overuse are worthy of concern and demand an urgent solution. Bacillus amyloliquefaciens TL106 has been isolated from cold- and disease-resistant Tibetan pigs in Linzhi, Tibet. It significantly improved the growth performance, decreased diarrhea, increased the absorption of crude substances, and regulated the gut flora homeostasis in Duroc×Landrace×Yorkshire weaned piglets. As an antibiotic candidate, TL106 perfectly displayed its probiotic potential and pollution-free properties.

Abstract Background Limited data is available on retinal vessel morphology in the north China. The study aimed to evaluate the prevalence of retinal vascular abnormalities (RVAs) and investigate their associations with the self-reported diagnosis of cardiovascular and cerebrovascsular diseases (CCVds) in a rural adult population of northeast China. Methods A population-based, cross-sectional study was conducted, using the cluster random sampling method. One eye of each participant was photographed with a non-mydriatic fundus camera. RVAs including focal and general arteriolar narrowing (FAN and GAN), arteriovenous nicking (AVN), arteriolar sheathing (AS), and retinopathy were evaluated. Data on self-reported diagnosis of cardiovascular and cerebrovascular diseases and status of smoking and alcohol drinking were obtained from questionnaires. Results Among the 6267 participants with an age ≥ 50 years, photographs were obtained of 99.2%, with quality sufficient to perform retinal evaluations in 82.5%. The prevalence of FAN, AVN, AS, retinopathy and GAN were 9.1, 8.9, 5.0, 6.6 and 6.2%, respectively. All the retinal lesions were associated with hypertension (all P

Pinus tabulaeformis plantations have been established around northern China to restore degraded land and provide timber or fuelwood. In recent years, widely distributed monoculture P. tabulaeformis forests have been transformed into mixed forests due to various ecological problems. However, the current research on the influence of near-natural transformation of P. tabulaeformis on soil microbial diversity and community composition remains limited. Therefore, we examined the effect of forest conversion from monoculture Pinus tabuliformis (PT) to P. tabuliformis-Armeniaca vulgaris (PTAU), P. tabuliformis - Robinia pseudoacacia (PTRP), P. tabuliformis - Vitex negundo L. var. heterophylla (PTVN) forests on soil microbial community diversity and composition. The results indicated that compared to PT, PTAU, PTVN, and PTRP could enhance the soil pH, TC, TN, AN, and AK in different degrees, the most obvious in PTAU. Near-natural transformation of P. tabuliformis could improve soil bacterial Pielou_e index, and Simpson index, as well as soil fungal Chao1 index. Proteobacteria and Ascomycota were the dominant soil microbial community at the phylum level. What’s more, both soil bacterial and fungal community among PT, PTAU, PTRP and PTVN showed clear different, and PTAU obviously altered the soil microbial community structure. Proteobacteria was the predominant group in PT, while, Gemmatimonadetes enriched in PTVN. Ascomycota was the predominant group in PTAU, while, Basidiomycota was the predominant group in PTRP. Near-natural transformation of P. tabuliformis could change soil microbial community via altering soil characteristics. In brief, our research results revealed the influence of tree composition and soil nutrient availability on soil microbial diversity and composition, and provided management guidance for introduction soil microbial community in forest protection and management.

The intercropping of nitrogen-fixing and non-nitrogen-fixing tree species changed the availability of soil nitrogen and soil microbial community structure and then affected the regulation process of soil carbon and nitrogen cycle by microorganisms in an artificial forest. However, there is no consensus on the effect of soil nitrogen on soil microorganisms. In this study, the intercropping of mulberry and twigs was completed through pot experiments. Total carbon, total nitrogen, and total phosphorus in the rhizosphere soil were determined, and the composition and structure of the soil microbial community were visualized by PCR amplification and 16S rRNA ITS sequencing. The analysis found that the intercropping of Morus alba L. and Lespedeza bicolor Turcz. had no significant effect on soil pH but significantly increased the contents of total carbon, total nitrogen, and total phosphorus in the soil. The effect on the alpha diversity of the bacterial community was not significant, but the effect on the evenness and diversity of the fungal community was significant (p < 0.05). It was also found that soil nutrients had no significant effect on bacterial community composition but had a significant effect on the diversity within the fungal community. This study added theoretical support for the effects of intercropping between non-nitrogen-fixing tree species and nitrogen-fixing tree species on soil nutrients and microbial community diversity.

Tibial dyschondroplasia (TD) is a metabolic disease of young poultry that affects bone andcartilage's growth. It mostly occurs in broilers due to thiram toxicity in the feed. In this disease, tibial cartilage is not yet ripe for ossification, but it also results in lameness, death, and moral convictions of commercial poultry due to numerous apoptotic changes on cell level. These changes serve a cardinal role in this situation. Many potential problems indicate that chlorogenic acid (CGA) performs an extensive role in controlling apoptosis's perception. However, the actual role of CGA in TD affected chondrocytes in-vitro is still unidentified. The current study investigates the imperceptible insight of CGA on chondrocyte’s apoptosis via B-cell lymphoma 2 (Bcl-2), Bcl-2 associated x-protein (Bax), and Caspase-3 with CD147 signalling. The expression of these markers was investigated by Immunofluorescence, western blot analysis, and reverse transcription-quantitative polymerase chain (RT-qPCR). Chondrocytes from the growth plate of tibia were isolated, cultured, and processed. A sub-lethal thiram (2.5 μg/mL) was used to induce cytotoxicity and then treated with an optimum dose (40 μg/ mL) of CGA. According to the results, thiram distorted chondrocyte cells with enhanced apoptotic rate. But, in case of CGA, high expression of CD147 enhanced cell viability of chondrocytes, accompanied by downregulation of Bax/Caspase-3 signalling with the upregulation of Bcl-2. The first possibility has ruled out in the present study by the observation that the cells apoptosis marker, Caspase-3 showed a significant change in CD147 overexpressing cells. Conversely, immunodepletion of CD147 with enhanced cleavage of Caspase-3, indicating the activation of apoptosis in chondrocytes cells. Therefore, these findings suggest a novel insight about CD147 in thiram induced TD about the regulation of Bcl-2/Bax/Caspase-3 apoptosis-signalling axis.