Study of the Prediction of Vibrations in Soft Soil Foundations Based on Field Tests.

To explore the prediction of vibrations in soft soil foundations, in light of the construction of laboratories with microvibration requirements on soft soil foundations which are subject to the limitations of urban land planning, field testing was conducted, and the soil surface vibration responses were recorded at different distances from a road under various highway traffic loads. By analyzing the data which summarize the characteristics of soft soil foundations, it is clarified that the vibration response of soft soil foundations mainly occurs at low frequencies, and the vibration response under road traffic loads is prone to resonance at the natural frequency of soft soil foundations. Subsequently, a new vibration prediction method based on the vibration transmission ratio is proposed, and its effectiveness and accuracy based on transmissibility are verified. This research study provides a reference for laboratories constructed on soft soil and for surrounding traffic planning.

Implementation of near-infrared spectroscopy and convolutional neural networks for predicting particle size distribution in fluidized bed granulation.

Monitoring the particle size distribution (PSD) is crucial for controlling product quality during fluidized bed granulation. This paper proposed a rapid analytical method that quantifies the D10, D50, and D90 values using a Convolutional Block Attention Module-Convolutional Neural Network (CBAM-CNN) framework tailored for deep learning with near-infrared (NIR) spectroscopy. This innovative framework, which fuses CBAM with CNN, excels at extracting intricate features while prioritizing crucial ones, thereby facilitating the creation of a robust multi-output regression model. To expand the training dataset, we incorporated the C-Mixup algorithm, ensuring that the deep learning model was trained comprehensively. Additionally, the Bayesian optimization algorithm was introduced to optimize the hyperparameters, improving the prediction performance of the deep learning model. Compared with the commonly used Partial Least Squares (PLS), Support Vector Machine (SVM), and Artificial Neural Network (ANN) models, the CBAM-CNN model yielded higher prediction accuracy. Furthermore, the CBAM-CNN model avoided spectral preprocessing, preserved the spectral information to the maximum extent, and returned multiple predicted values at one time without degrading the prediction accuracy. Therefore, the CBAM-CNN model showed better prediction performance and modeling convenience for analyzing PSD values in fluidized bed granulation.

Oridonin employs interleukin 1 receptor type 2 to treat noise-induced hearing loss by blocking inner ear inflammation.

NOD-like receptor protein 3 (NLRP3) inflammasomes trigger the inflammatory cascades and participate in various inflammatory diseases, including noise-induced hearing loss (NIHL) caused by oxidative stress. Recently, the anti-inflammatory traditional medicine oridonin (Ori) has been reported to provide hearing protection in mice after noise exposure by blocking the NLRP3-never in mitosis gene A-related kinase 7 (NEK7)-inflammasome complex assembly. Using RNA sequencing analysis, we further elucidated that interleukin 1 receptor type 2 (IL1R2) may be another crucial factor regulated by Ori to protect NIHL. We observed that IL1R2 expression was localized in spiral ganglion neurons, inner and outer hair cells, in Ori-treated mouse cochleae. Additionally, we confirmed that ectopic overexpression of IL1R2 in the inner ears of healthy mice using an adeno-associated virus delivery system significantly reduced noise-induced ribbon synapse lesions and hearing loss by blocking the "cytokine storm" in the inner ear. This study provides a novel theoretical foundation for guiding the clinical treatment of NIHL.

Structural characterization and functional analysis of juvenile hormone acid methyltransferase JHAMT3 from the silkworm, Bombyx mori.

Juvenile hormone acid methyltransferase (JHAMT) is a rate-limiting enzyme of juvenile hormone (JH) biosynthesis in insects. It transfers the methyl group of S-adenosyl methionine to either the carboxyl group of JH acids or farnesoic acid to produce JH. Six JHAMT paralogues have been identified in the silkworm (Bombyx mori); among them, JHAMT1 and JHAMT2 display a methyltransferase activity. Here, the three-dimensional crystal structure of inactive JHAMT3 and the binary complex of JHAMT3 with its cofactor S-adenosyl-l-homocysteine were determined through X-ray crystallization. Comparative structural analysis revealed that JHAMT3 adopted a similar structural pattern to that of functional JHAMT2, which comprised one core Rossmann fold domain and one substrate-binding domain. Similar to JHAMT2, JHAMT3 underwent a conformational change at the Rossmann fold domain because of cofactor binding, which promoted ligand accommodation. However, it exhibited a relatively rigid substrate-binding pocket compared with that of JHAMT2. JHAMT3 was also highly expressed in the silk gland of fourth- and fifth-instar B. mori larvae. The results of expression profiling combined with activity analysis suggested that JHAMT3 might function as a binding protein of JH acids for the regulation of JH acid titers. These findings provide a structural basis for enhancing the understanding of the physiological function of JHAMT3 and a rational framework for the development of potent and specific inhibitors of JHAMT family members.

Prediction of Traffic Vibration Environment of Ancient Wooden Structures Based on the Response Transfer Ratio Function.

Traffic-induced vibration is increasingly affecting people's lives, which necessitates scrutiny of the environmental vibrations caused by traffic. This paper proposed a vibration prediction method suitable for the ancient wooden structures subjected to traffic-induced vibrations based on the multi-point response transfer ratio function. The accuracy of the proposed approach was also checked by comparing the predicted results with the measured results in the context of both the time domain and frequency domain. Subsequently, the environmental vibrations due to heavy-duty trucks passing at various speeds were measured, and the measurements were utilized as the input vibration excitation to assess the structural vibration of the Feiyun Pavilion. The structural safety was evaluated according to the "Technical specifications for protecting historic buildings against man-made vibration". In order to meet the structural safety requirements of the Feiyun Pavilion, it is strongly recommended to limit the type and speed of vehicles in the nearby area.

Structural basis for juvenile hormone biosynthesis by the juvenile hormone acid methyltransferase.

Juvenile hormone (JH) acid methyltransferase (JHAMT) is a rate-limiting enzyme that converts JH acids or inactive precursors of JHs to active JHs at the final step of JH biosynthesis in insects and thus presents an excellent target for the development of insect growth regulators or insecticides. However, the three-dimensional properties and catalytic mechanism of this enzyme are not known. Herein, we report the crystal structure of the JHAMT apoenzyme, the three-dimensional holoprotein in binary complex with its cofactor S-adenosyl-l-homocysteine, and the ternary complex with S-adenosyl-l-homocysteine and its substrate methyl farnesoate. These structures reveal the ultrafine definition of the binding patterns for JHAMT with its substrate/cofactor. Comparative structural analyses led to novel findings concerning the structural specificity of the progressive conformational changes required for binding interactions that are induced in the presence of cofactor and substrate. Importantly, structural and biochemical analyses enabled identification of one strictly conserved catalytic Gln/His pair within JHAMTs required for catalysis and further provide a molecular basis for substrate recognition and the catalytic mechanism of JHAMTs. These findings lay the foundation for the mechanistic understanding of JH biosynthesis by JHAMTs and provide a rational framework for the discovery and development of specific JHAMT inhibitors as insect growth regulators or insecticides.

The Pseudomonas aeruginosa Secreted Protein PA3611 Promotes Bronchial Epithelial Cell Epithelial-Mesenchymal Transition via Integrin αvß6-Mediated TGF-ß1-Induced p38/NF-κB Pathway Activation.

Pseudomonas aeruginosa (PA) is an important pathogen that has been proven to colonize and cause infection in the respiratory tract of patients with structural lung diseases and to lead to bronchial fibrosis. The development of pulmonary fibrosis is a complication of PA colonization of the airway, resulting from repeated infection, damage and repair of the epithelium. Bronchial epithelial cell epithelial-mesenchymal transition (EMT) plays a vital role in bronchial fibrosis. To date, research on bronchial epithelial cell EMT caused by PA-secreted virulence factors has not been reported. Here, we found that PA3611 protein stimulation induced bronchial epithelial cell EMT with mesenchymal cell marker upregulation and epithelial cell marker downregulation. Moreover, integrin αvß6 expression and TGF-ß1 secretion were markedly increased, and p38 MAPK phosphorylation and NF-κB p65 subunit phosphorylation were markedly enhanced. Further research revealed that PA3611 promoted EMT via integrin αvß6-mediated TGF-ß1-induced p38/NF-κB pathway activation. The function of PA3611 was also verified in PA-infected rats, and the results showed that ΔPA3611 reduced lung inflammation and EMT. Overall, our results revealed that PA3611 promoted EMT via integrin αvß6-mediated TGF-ß1-induced p38/NF-κB pathway activation, suggesting that PA3611 acts as a crucial virulence factor in bronchial epithelial cell EMT and is a potential target for the clinical treatment of bronchial EMT and fibrosis caused by chronic PA infection.

Structural characterization and functional analysis of juvenile hormone diol kinase from the silkworm, Bombyx mori.

Juvenile hormone diol kinase (JHDK) is an important enzyme involved in the juvenile hormone metabolism pathway, which catalyzes the phosphorylation of juvenile hormone diol to form the polar metabolite JH diol phosphate. Here, we reported the first crystal structure of insect JHDK from Bombyx mori, BmJHDK-L2, determined at a resolution of 1.22 Å. The structure of BmJHDK-L2 mainly comprises of eight α-helical segments linked with loops, forming four helix-loop-helix motifs. In these four helix-loop-helix motifs with only one calcium ion bound in the first motif. Circular dichroism spectra indicated that BmJHDK-L2 has strong thermal stability, which is independent of the divalent cation. The structure of BmJHDK-L2 further allowed us to define an ATP-binding site using computational simulation and binding assays, providing a structural basis for development of inhibitor of JHDK. Moreover, the expression profile of BmJHDK-L2 indicated a predominant role in juvenile hormone metabolism in the Malpighian tubules of silkworm. Collectively, these findings expand our knowledge regarding the structural and biochemical features of insect JHDK proteins.

Overexpression of Gloverin2 in the Bombyx mori silk gland enhances cocoon/silk antimicrobial activity.

The Bombyx mori cocoon/silk possesses many immune-related components, including protease inhibitors, seroins, and antimicrobial peptides, which likely help to protect the pupating larva from infection. However, the natural antimicrobial activity of the B. mori cocoon/silk is still too weak for biomedical applications. With the goal of enhancing this natural activity, we constructed a transgenic vector to overexpress the B. mori antimicrobial peptide Gloverin2 (BmGlv2) under control of the silk gland-specific Serion1 promoter. Transgenic silkworms were generated via embryo microinjection. A low level of BmGlv2 was expressed in the non-transgenic silk gland, but BmGlv2 was efficiently overexpressed and proteolytically activated in the transgenic line. Overexpressed BmGlv2 was secreted and incorporated into the silk during spanning without affecting cocoon/silk formation. Moreover, the transgenic cocoon/silk had significantly greater inhibitory activity against bacteria and fungi than the non-transgenic cocoon/silk. This strategy could help enhance the antimicrobial performance and biomedical application of silk.

8-Hydroxy-2'-deoxyguanosine as a biomarker of oxidative stress in acute exacerbation of chronic obstructive pulmonary disease

Background/aim: 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a biomarker of oxidative stress and has been implicated in many diseases. The aim of this study was to investigate the clinical value of plasma 8-OHdG level in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Materials and methods: A total of 154 subjects were enrolled in this study, including 20 healthy volunteers, 24 COPD patients in the stable phase, and 110 AECOPD patients. Peripheral blood samples, demographic information, and clinical characteristics were collected from all subjects at the time of being recruited into the study. Plasma 8-OHdG level was detected by enzyme-linked immunosorbent a ss ay. Results: 8-OHdG was increased in patients with AECOPD compared to healthy subjects and patients with stable COPD, especially in smokers. It also increased with the GOLD stage, mMRC grade, CAT score, and group level of combined COPD assessment. Additionally, further analysis revealed that 8-OHdG was negatively correlated with FEV1, FEV1% predicted, and FEV1/FVC and positively correlated with C-reactive protein, procalcitonin, and neutrophil CD64. Conclusion: 8-OHdG is associated with spirometric severity, symptomatic severity, exacerbation risk, and inflammatory biomarkers in AECOPD patients, suggesting it as a promising biomarker for reflecting disease severity and guiding the choice of optimal therapeutic decision.

Fibroinase and its physiological inhibitors involved in the regulation of silk gland development in the silkworm, Bombyx mori.

Fibroinase, a cathepsin L-like cysteine protease, was previously identified in the silk gland of the silkworm, Bombyx mori. It shows high degradation activity during the pre-pupa period, when the silk gland undergoes apoptosis and remodeling. Here, we recombinantly expressed pro-fibroinase and activated it in vitro. Fibroinase showed optimal hydrolytic activity at pH 4.0 and its optimum temperature was about 42 °C. One physiological inhibitor, B. mori cysteine protease inhibitor (BCPI) was found, which showed strong inhibitory activity against fibroinase. The inhibitory reaction was caused by the formation of a non-covalent complex; this is in contrast to a previously reported mode of fibroinase inhibition by Serpin18. Expression profiles and immunolocalization analysis demonstrated that fibroinase was involved in silk gland development by degrading silk proteins and apoptosis/remodeling of silk glands at specific points. Furthermore, the comparison of the temporal expression of fibroinase and its inhibitors, BCPI and Serpin18, indicated that these inhibitors were involved in the silk gland development by regulating the activity of fibroinase from the fifth instar until the early spinning stage. These findings improve our understanding of the mechanism of protease regulation and its inhibitors in silk gland development.

Antibacterial Mechanism of Gloverin2 from Silkworm, Bombyx mori.

Gloverin is one of the glycine-rich antimicrobial peptide exclusively found in Lepidoptera insects. It is generally activated through the innate immune system in insects. In this study, recombinant Gloverin2 from Bombyx mori (BmGlv2) was synthesized using a prokaryotic expression system. Circular dichroism spectroscopy showed that the recombinant BmGlv2 has random coil structure, which is relatively stable at the temperatures ranging from 15 to 82.5 °C. Antimicrobial activity analysis revealed that BmGlv2 significantly inhibited the growth of gram-negative bacteria, Escherichia coli JM109 and Pseudomonas putida, by disrupting cell integrity. Western blotting and immunofluorescence analyses suggested that BmGlv2 absorbed on the cell surface after incubation, which might be the first step in the antibacterial process. Our results also proved that the cell wall component lipopolysaccharides (LPS) induce a conformational change in BmGlv2 from a random coil to α-helix. Subsequently, α-helical BmGlv2 would recruit more BmGlv2 and form higher aggregation state. Collectively, these findings expand our understanding of antibacterial mechanism of BmGlv2.

Geniposide demonstrates anti-inflammatory and antiviral activity against pandemic A/Jiangsu/1/2009 (H1N1) influenza virus infection in vitro and in vivo.

BACKGROUND: Influenza A viruses (IAVs) have been a great threat to human health for centuries, without effective control. Geniposide, a main iridoid glycoside compound extracted from Gardenia jasminoides Ellis fruit, possesses various biological activities including anti-inflammation and anti-virus. METHODS: Madin-Darby canine kidney (MDCK) cells were infected with pandemic A/Jiangsu/1/2009 (H1N1) influenza virus in vitro. Cytotoxicity and antiviral activity of geniposide were estimated by MTT assay. The influenza respiratory tract infection murine model was established by intranasal instillation of pandemic A/Jiangsu/1/2009 (H1N1) influenza virus. One day after infection, the mice were administered with geniposide (5, 10 or 20 mg/kg/day) or the neuraminidase inhibitor (NAI) peramivir (30 mg/kg/day). Body weight, survival time, viral titre and lung index of the mice were measured. The sandwich enzyme-linked immunosorbent assay (ELISA) was used to examine levels of inflammatory cytokines. RESULTS: The data showed that geniposide had little cytotoxicity on MDCK cells and protected them from pandemic A/Jiangsu/1/2009 (H1N1) influenza virus-induced cell injury. In the infected mice, geniposide treatment significantly restored the body weights, decreased the mortality, alleviated viral titres and virus-induced lung lesions. Geniposide substantially inhibited the virus-induced alveolar wall changes, alveolar haemorrhage and neutrophil-infiltration in lung tissues. Levels of inflammatory mediators, including tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-4, IL-6 and IL-10 were also markedly altered after treatment with geniposide. CONCLUSIONS: Our investigation suggested that geniposide effectively inhibited cell damage mediated by pandemic A/Jiangsu/1/2009 (H1N1) influenza virus and mitigated virus-induced acute inflammation.

Chrysin alleviates allergic inflammation and airway remodeling in a murine model of chronic asthma.

Asthma is a chronic airway inflammatory disorder and progresses mainly due to airway remodeling. Chrysin, a natural flavonoid, has been reported to possess multiple biologic activities, including anti-inflammation, anti-oxidation and anti-proliferation. The present study aimed to investigate whether chrysin could relieve allergic airway inflammation and remodeling in a murine model of chronic asthma and the mechanism involved. The female BALB/c mice sensitized and challenged with ovalbumin (OVA) successfully developed airway hyperresponsiveness (AHR), inflammation and remodeling. The experimental data showed that chrysin could alleviate OVA-induced AHR. Chrysin could also reduce OVA-induced increases in the number of inflammatory cells, especially eosinophils, interleukin (IL) -4, and IL-13 in bronchoalveolar lavage fluid (BALF) and total IgE in serum. The decreased interferon-γ (IFN-γ) level in BALF was also upregulated by chrysin. In addition, inflammatory cell infiltration, goblet cell hyperplasia and the expression of α-smooth muscle actin (α-SMA) around bronchioles were suppressed by chrysin. Furthermore, the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) could be decreased by chrysin, which are associated with airway smooth muscle cell (ASMC) proliferation. These results indicate the promising therapeutic effect of chrysin on chronic asthma, especially the progression of airway remodeling.

Chrysin inhibits human airway smooth muscle cells proliferation through the extracellular signal-regulated kinase 1/2 signaling pathway.

Asthma is a chronic airway inflammatory disease characterized by an increased mass of airway smooth muscle (ASM). Chrysin (5,7-dihydroxyflavone), a natural flavonoid, has been shown to exert multiple biological activities, including anti-inflammatory, anti-proliferative and anti-oxidant effects, as well as the potency to ameliorate asthma in animal models. The objective of the present study was to identify the underlying mechanism of the therapeutic effects of chrysin. The impact of chrysin on basal and platelet-derived growth factor (PDGF)-induced proliferation and apoptosis of human airway smooth muscle cells (HASMCs) was investigated. Furthermore, the activation of the extracellular signal-regulated protein kinase (ERK) signaling pathway was evaluated in HASMCs. The results revealed that chrysin significantly inhibited basal as well as PDGF-induced HASMC proliferation, most likely through the suppression of ERK1/2 phosphorylation. However, chrysin did not significantly reduce PDGF-induced apoptosis of HASMCs. The present study indicated that chrysin may be a promising medication for controlling airway remodeling and clinical manifestations of asthma.