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Peptide mapping is an important tool used to confirm that the correct sequence has been expressed for a protein and to evaluate protein post-translational modifications (PTMs) that may arise during the production, processing, or storage of protein drugs. Our new orally administered drug (Ab-1), a single-domain antibody, is highly stable and resistant to proteolysis. Analysis via the commonly used tryptic mapping method did not generate sufficient sequence coverage. Alternative methods were needed to study the Ab-1 drug substance (75 mg/mL) and drug product (3 mg/mL). To meet these analytical needs, we developed two new peptide mapping methods using lysyl endopeptidase (Lys-C) digestion. These newly developed protein digestion protocols do not require desalting/buffer-exchange steps, thereby reducing sample preparation time and improving method robustness. Additionally, the protein digestion is performed under neutral pH with methionine acting as a scavenger to minimize artifacts, such as deamidation and oxidation, which are induced during sample preparation. Further, the method for low-concentration samples performs comparably to the method for high-concentration samples. Both methods provide 100% sequence coverage for Ab-1, and, therefore, enable comprehensive characterization for its product quality attribute (PQA) assessment. Both methods can be used to study other antibody formats. [ABSTRACT FROM AUTHOR]

An ideal artificial bone implant should have similar mechanical properties and biocompatibility to natural bone, as well as an internal structure that facilitates stomatal penetration. In this work, 3D printing was used to fabricate and investigate artificial bone composites based on HA-ZrO2-PVA. The composites were proportionally configured using zirconia (ZrO2), hydroxyapatite (HA) and polyvinyl alcohol (PVA), where the ZrO2 played a toughening role and PVA solution served as a binder. In order to obtain the optimal 3D printing process parameters for the composites, a theoretical model of the extrusion process of the composites was first established, followed by the optimization of various parameters including the spray head internal diameter, extrusion pressure, extrusion speed, and extrusion line width. The results showed that, at the optimum parameters of a spray head diameter of 0.2 mm, extrusion pressure values ranging from 1–3 bar, a line spacing of 0.8–1.5 mm, and a spray head displacement range of 8–10 mm/s, a better structure of biological bone scaffolds could be obtained. The mechanical tests performed on the scaffolds showed that the elastic modulus of the artificial bone scaffolds reached about 174 MPa, which fulfilled the biomechanical requirements of human bone. According to scanning electron microscope observation of the scaffold sample, the porosity of the scaffold sample was close to 65%, which can well promote the growth of chondrocytes and angiogenesis. In addition, c5.18 chondrocytes were used to verify the biocompatibility of the composite materials, and the cell proliferation was increased by 100% when compared with that of the control group. The results showed that the composite has good biocompatibility. [ABSTRACT FROM AUTHOR]

Heterogeneity of therapeutic Monoclonal antibody (mAb) drugs are due to protein variants generated during the manufacturing process. These protein variants can be critical quality attributes (CQAs) depending on their potential impact on drug safety and/or efficacy. To identify CQAs and ensure the drug product qualities, a thorough characterization is required but challenging due to the complex structure of biotherapeutics. Past characterization studies for basic and acidic variants revealed that full characterizations were limited to the basic charge variants, while the quantitative measurements of acidic variants left gaps. Consequently, the characterization and quantitation of acidic variants are more challenging. A case study of a therapeutic mAb1 accounted for two-thirds of the enriched acidic variants in the initial characterization study. This led to additional investigations, closing the quantification gaps of mAb1 acidic variants. This work demonstrates that a well-designed study with the right choices of analytical methods can play a key role in characterization studies. Thus, the updated strategies for more complete antibody charge variant characterization are recommended. [ABSTRACT FROM AUTHOR]

Objective We compared failure patterns and survival after elective nodal irradiation (ENI) or involved-field irradiation (IFI) in patients with thoracic esophageal squamous cell carcinoma (ESCC), clinical stage T2-4N0M0, to determine whether IFI is feasible for such patients. Methods Between 2005 and 2015, 126 patients with clinical stage T2-4N0M0 thoracic ESCC who received definitive concurrent chemoradiotherapy in Shandong Cancer Hospital and Institute and who had complete data, were analyzed retrospectively. Of those patients, 49 received IFI, and 77 received ENI. In the IFI group, the radiation field included the primary tumour, with a 3-cm to 4-cm margin in the craniocaudal direction, and the elective irradiation was delivered to the adjacent regional lymphatics according to the location of the primary tumour. Patterns of failure were classified using the first site of failure, which included primary tumour failure, regional lymph node failure, and distant metastasis. Results Median progression-free survival was 20 months [95% confidence interval (CI): 7.87 months to 39.2 months] in the IFI group and 30 months (95% CI: 17.4 months to 44.6 months) in the ENI group (p = 0.580). Median overall survival (OS) was 36 months (95% CI: 21.9 months to 50.1 months) in the IFI group and 38 months (95% CI: 26.1 months to 49.9 months) in the ENI group (p = 0.761). The estimated 1-year, 3-year, and 5-year os rates were, respectively, 87.8%, 49.4%, and 32.3% for the IFI patients and 92.2%, 52.0%, and 28.9% for the ENI patients. Disease persistence and primary lesion recurrence after complete remission (CR) were the most frequent causes of treatment failure in the patients overall (83 of 124, 66.9%). Of the 66 patients achieving a clinical CR, 25 experienced recurrence of the primary lesion, 12 experienced distant relapse, 10 experienced regional nodal failure, and 2 experienced an isolated recurrence. No significant differences in the pattern of failure or in the incidences of grade 3 or greater treatmentrelated myelosuppression or esophagitis were found between the IFI and ENI groups. Conclusions In patients with thoracic ESCC clinical stage T2-4N0M0 receiving definitive chemoradiotherapy, failure patterns and os were similar with either eni or IFI. Large prospective randomized studies are needed to further investigate and verify those results in this subgroup of patients. [ABSTRACT FROM AUTHOR]

Background The quality of data comparing care at the end of life (eol) in cancer patients across Canada is poor. This project used identical cohorts and definitions to evaluate quality indicators for eol care in British Columbia, Alberta, Ontario, and Nova Scotia. Methods This retrospective cohort study of cancer decedents during fiscal years 2004-2009 used administrative health care data to examine health service quality indicators commonly used and previously identified as important to quality eol care: emergency department use, hospitalizations, intensive care unit admissions, chemotherapy, physician house calls, and home care visits near the eol, as well as death in hospital. Crude and standardized rates were calculated. In each province, two separate multivariable logistic regression models examined factors associated with receiving aggressive or supportive care. Results Overall, among the identified 200,285 cancer patients who died of their disease, 54% died in a hospital, with British Columbia having the lowest standardized rate of such deaths (50.2%). Emergency department use at eol ranged from 30.7% in Nova Scotia to 47.9% in Ontario. Of all patients, 8.7% received aggressive care (similar across all provinces), and 46.3% received supportive care (range: 41.2% in Nova Scotia to 61.8% in British Columbia). Lower neighbourhood income was consistently associated with a decreased likelihood of supportive care receipt. Interpretation We successfully used administrative health care data from four Canadian provinces to create identical cohorts with commonly defined indicators. This work is an important step toward maturing the field of eol care in Canada. Future work in this arena would be facilitated by national-level data-sharing arrangements. [ABSTRACT FROM AUTHOR]

Background Delineating the nodal clinical target volume (CTVn) remains a challenging task in patients with cervical or upper thoracic esophageal carcinoma (EC). In particular, the extent of the lymph area that should be included in the irradiation field remains controversial. In the present study, the extent of the ctvn was determined based on the incidence of lymph node involvement mapped by computed tomography (CT) imaging. Methods Our study included 468 patients who were diagnosed with cervical and upper thoracic ec and who received staging information between June 2005 and April 2011. The anatomic distribution of metastatic regional lymph nodes was mapped using ct images and grouped using the levels established by the Radiation Therapy Oncology Group. The probability of the various groups being involved was examined. If a lymph node group had a probability of 10% or more of being involved, it was considered at high risk for metastasis, and elective treatment as part of the CTVn was recommended. Results Lymph node involvement was mapped by CT in 256 patients (54.7%). Not all lymph node groups should be included in the CTVn. For cervical lesions, the involved lymph nodes were located mainly between the hyoid bone and the arcus aortae; the recommended CTVn should consist of the neck lymph nodes at levels iii and iv (supraclavicular group) and thoracic groups 2 and 3P. In upper thoracic EC patients, most of the involved lymph nodes were distributed between the cricoid cartilage and the subcarinal area; the CTVn should cover the supraclavicular group and thoracic nodal groups 2, 3P, 4, 5, and 7. Conclusions Our ct-based study indicates a specific distribution and incidence of metastatic lymph node groups in patients with cervical and upper thoracic EC. The results suggest that regional lymph node groups should be electively included in the CTVn for precise radiation administration. [ABSTRACT FROM AUTHOR]

Foxtail millet (Setaria italica), which originated in China, has a strong tolerance to low nutrition stresses. However, the mechanism of foxtail millet tolerance to low-nitrogen stress is still unknown. In this study, the transcriptome of foxtail millet under low-nitrogen stress was systematically analyzed. Expression of 1891 genes was altered, including 1318 up-regulated genes and 573 down-regulated genes. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that 3% of these genes were involved in membrane transport and 5% were involved in redox processes. There were 74 total transcription factor (TF) genes in the DEGs (differentially expressed genes), and MYB-like transcription factors accounted for one-third (25) of the TF genes. We systematically analyzed the characteristics, expression patterns, chromosome locations, and protein structures of 25 MYB-like genes. The analysis of gene function showed that Arabidopsis and rice overexpressing SiMYB3 had better root development than WT under low-nitrogen stress. Moreover, EMSA results showed that SiMYB3 protein could specifically bind MYB elements in the promoter region of TAR2, an auxin synthesis related gene and MYB3-TAR2 regulate pair conserved in rice and foxtail millet. These results suggested that SiMYB3 can regulate root development by regulating plant root auxin synthesis under low-nitrogen conditions. [ABSTRACT FROM AUTHOR]

Designing and standardizing drug formulations are crucial for ensuring the safety and efficacy of medications. Nanomedicine utilizes nano drug delivery systems and advanced nanodevices to address numerous critical medical challenges. Currently, oral and intranasal aerosol drug delivery (OIADD) is the primary method for treating respiratory diseases worldwide. With advancements in disease understanding and the development of aerosolized nano drug delivery systems, the application of OIADD has exceeded its traditional boundaries, demonstrating significant potential in the treatment of non-respiratory conditions as well. This study provides a comprehensive overview of the applications of oral and intranasal aerosol formulations in disease treatment. It examines the key challenges limiting the development of nanomedicines in drug delivery systems, formulation processes, and aerosol devices and explores the latest advancements in these areas. This review aims to offer valuable insights to researchers involved in the development of aerosol delivery platforms.

As a small-molecule gelator used as a stabilizer in gel emulsions, it has numerous advantages, such as low dosage, independence from phase ratios, and ease of control. In this study, a cholesterol derivative (CSA) was designed and synthesized to be used as a stabilizer for gel emulsions. Gelation experiments demonstrated that this small molecule could gelate various organic solvents, including linear alkanes, toluene, isoamyl alcohol, and acetone. Based on these gelation experiments, a series of gel emulsions were prepared with water as the dispersed phase and an organic solvent immiscible with water as the continuous phase. Finally, the gelation behavior of the gelator/water/toluene and gelator/water/cyclohexane systems was investigated, exploring the effects of different systems and varying water content within the same system on the structure and stability of the gel emulsions. Studies have shown that the gel emulsion prepared from the gelator/water/toluene system exhibits superior stability, likely due to the molecular self-assembly behavior of this cholesterol derivative exhibited in the water/toluene biphasic system. The research results provide a basis for using gel emulsions as templates to prepare porous materials and adjust their internal structure, ultimately laying a solid foundation for applying these porous materials in fields such as adsorption and catalysis.

The attention mechanism is essential to convolutional neural network (CNN) vision backbones used for sensing and imaging systems. Conventional attention modules are designed heuristically, relying heavily on empirical tuning. To tackle the challenge of designing attention mechanisms, this paper proposes a novel probabilistic attention mechanism. The key idea is to estimate the probabilistic distribution of activation maps within CNNs and construct probabilistic attention maps based on the correlation between attention weights and the estimated probabilistic distribution. The proposed approach consists of two main components: (i) the calculation of the probabilistic attention map and (ii) its integration into existing CNN architectures. In the first stage, the activation values generated at each CNN layer are modeled by using a Laplace distribution, which assigns probability values to each activation, representing its relative importance. Next, the probabilistic attention map is applied to the feature maps via element-wise multiplication and is seamlessly integrated as a plug-and-play module into existing CNN architectures. The experimental results show that the proposed probabilistic attention mechanism effectively boosts image classification accuracy performance across various CNN backbone models, outperforming both baseline and other attention mechanisms.

Smart fibers with tunable luminescence properties, as a new form of visual output, present the potential to revolutionize personal living habits in the future and are receiving more and more attention. However, a huge challenge of smart fibers as wearable materials is their stretching capability for seamless integration with the human body. Herein, stretchable thermochromic fluorescent fibers are prepared based on self-crystallinity phase change, using elastic polyurethane (PU) as the fiber matrix, to meet the dynamic requirements of the human body. The switching fluorescence-emitting characteristic of the fibers is derived from the reversible conversion of the dispersion/aggregation state of the fluorophore coumarin 6 (C6) and the quencher methylene blue (MB) in the phase-change material hexadecanoic acid (HcA) during heating/cooling processes. Considering the important role of phase-change materials, thermochromic fluorescent dye is encapsuled in the solid state via the piercing-solidifying method to avoid the dissolution of HcA by the organic solvent of the PU spinning solution and maintain excellent thermochromic behavior in the fibers. The fibers obtained by wet spinning exhibit good fluorescent emission contrast and reversibility, as well as high elasticity of 800% elongation. This work presents a strategy for constructing stretchable smart luminescence fibers for human-machine interaction and communications.

C-S lyase is a crucial enzyme responsible for the formation of sulfur-containing flavor compounds in Lentinula edodes . We investigated the involvement of C-S lyase in the synthesis of ergothioneine (EGT) in L. edodes , a high-producing edible mushroom. Through experimental and computational approaches, we identified Lecsl 2, a C-S lyase, as a key enzyme involved in EGT synthesis in L. edodes . We characterized the enzymatic catalytic mechanism of Egt1 and Egt2, the two enzymes primarily catalyzing EGT synthesis in fungi. The results showed that Egt1 interacted with His, SAM, and Cys to form the intermediate product Her-sul, while Egt2, a PLP-dependent enzyme, cleaved the C-S bond on Her-sul to produce EGT. However, our findings suggested that Egt2 in L. edodes might not form a covalent bond with PLP, unlike the previously reported catalytic mechanism of Egt2 involving covalent catalysis. The study provided new insights into the synthesis pathway of EGT in L. edodes and highlighted the need for further investigation into the catalytic mechanism of Egt2 in this species.

By combining molecular dynamics (MD) simulations and density functional theory (DFT), the influence of dye structure on the optical modulation properties of negative-mode guest-host liquid crystal (GHLC) systems was systematically investigated. Firstly, the reliability of the simulation method was validated by comparing the performance parameters of the GHLC system obtained from simulations with those from experimental results. Subsequently, a series of guest dye molecules, along with their mixtures with negative dielectric anisotropy mesogens, were designed and analyzed. This exploration focused on how variations in dye terminal chain lengths, substitution positions, and substituent group properties affect dye molecular geometry, dye alignment within the host, transition dipole orientation, absorption spectra, and electronic excitation properties. Our findings suggest that dye molecules with a flexible terminal chain substitution of five carbon atoms, positioned at the 2 and 6 locations on the anthraquinone core, exhibit higher order parameters, favorable for enhancing dichroic performance. Moreover, introducing different α-substituents further influences the dye orientation and electronic behavior within the host. These results highlight that structural modifications of anthraquinone-based dyes allow for the design of high-dichroic-ratio materials with customized absorption properties. Overall, our results provide a beneficial understanding of the structure-property relation in GHLC systems, offering valuable guidance for designing high-performance dye molecules and advanced optoelectronic materials in future research.

Emamectin benzoate (EB) is a highly effective broad-spectrum insecticide and acaricide. However, because EB is easily degraded, the conventional formulations of EB are often overapplied. In this study, polylactic acid (PLA)-based microspheres were prepared using the modified solvent evaporation method for the controlled release of EB. The microspheres were optimized to achieve higher EB loading. The effects of process parameters on the properties of microspheres, including encapsulation efficiency (EE), particle size, and pesticide loading, were investigated. Additionally, the controlled release behavior of EB microspheres was compared with that of conventional EB emulsifiable concentrate (EC). Spherical-shaped microspheres were obtained with an EE reaching 90.63 ± 1.90%, and introducing an external aqueous phase into the system can significantly enhance the EE of microspheres by over 30%. FTIR, DSC, and XRD analyses indicate that the preparation process of PLA microspheres was mainly physical encapsulation and had no chemical effect on EB. Notably, the EB microspheres displayed more potent control efficacy compared to commercial formulation EB EC against Plutella xylostella . The corrected mortality for the EB microspheres reached 90.00 ± 5.77% after 21 days of application, whereas the corrected mortality for the EB EC was only 19.23 ± 6.66% after 14 days of application. Our study demonstrates that EB-encapsulated PLA microspheres have strong potential as environmentally friendly control release EB formulations.

This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional infectious disease treatment center in China. Plasma levels of IL-35 at baseline were detected using ELISA. Plasma IL-35 levels in the HBV-ACLF group were the highest among all four groups. Furthermore, survivors exhibited significantly higher IL-35 levels than non-survivors ( p < 0.001). IL-35 levels correlated with MELD (r = -0.678, p < 0.001), COSSH-ACLF IIs (r = -0.581, p < 0.001), alpha-fetoprotein (AFP) (r = 0.433, p < 0.001), creatinine (Cr) (r =-0.396, p = 0.001), and lactate (r =-0.38, p =0.001). The combination of plasma IL-35 and MELD score had the highest mortality prediction efficiency, with an area under the curve (AUC) of 0.895 (95% CI: 0.812-0.978, p < 0.001), a sensitivity of 80.6%, and a specificity of 93.9%. Additionally, the Kaplan-Meier analysis revealed that lower levels of IL-35 (≤191.5pg/mL) were associated with poorer survival rates in HBV-ACLF patients ( p < 0.001). Our results demonstrated that IL-35 could be an effective predictive marker for the prognosis of HBV-ACLF and improve the predictive performance when combined with the MELD score.

Previous studies have revealed that muscle atrophy emerges as a significant challenge faced by astronauts during prolonged missions in space. A loss in muscle mass results in a weakening of skeletal muscle strength and function, which will not only contribute to a decline in overall physical performance but also elevate the risk of various age-related diseases. Skeletal muscle atrophy in the microgravity environment is thought to be associated with changes in energy metabolism, protein metabolism, calcium ion homeostasis, myostatin levels, and apoptosis. Modulating some pathways could be a promising approach to mitigating muscle atrophy in the microgravity environment. This review serves as a comprehensive summary of research on the impact of microgravity on skeletal muscle, with the aim of providing insights into its pathogenesis and the development of effective treatments., Competing Interests: The authors declare no conflicts of interest.

Background: Pseudomonas aeruginosa ( P. aeruginosa ) is a type of pathogen that takes advantage of opportunities to infect and form biofilm during infection. Inhibiting biofilm formation is a promising approach for the treatment of biofilm-related infections. Methods: Here, Y0-C10-HSL (N-cyclopentyl-n-decanamide) was designed, synthesized, and tested for its effect on biofilm formation, motility, and the Caenorhabditis elegans ( C. elegans ) survival assay. In addition, the molecular mechanism of Y0-C10-HSL on P. aeruginosa biofilm formation was explored using transcriptome analysis. Results: At a concentration of 200 μmol/L Y0-C10-HSL, biofilm and exopolysaccharides were decreased by 38.5% and 29.3%, respectively; Y0-C10-HSL effectively dispersed the pre-formed biofilm and inhibited the motility ability of P. aeruginosa ; and the C. elegans survival assay showed that Y0-C10-HSL was safe and provided protection to C. elegans against P. aeruginosa infection (the survival rates of C. elegans were higher than 74% and increased by 39%, 35.1%, and 47.5%, respectively, when treated with 200 μmol/L Y0-C10-HSL at 24, 48, and 80 h). Transcriptome analysis showed that 585 differentially expressed genes (DEGs) were found after treatment with 200 μmol/L Y0-C10-HSL, including 254 up-regulated DEGs and 331 down-regulated DEGs. The genes involved in the quorum sensing system and biofilm formation were down-regulated. Conclusions: Y0-C10-HSL inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa through down-regulated genes related to quorum sensing pathways and biofilm formation. These findings provide a theoretical foundation for the treatment and prevention of antibiotic resistance in clinical and environmental microorganisms such as P. aeruginosa .

Traffic flow forecasting is integral to transportation to avoid traffic accidents and congestion. Due to the heterogeneous and nonlinear nature of the data, traffic flow prediction is facing challenges. Existing models only utilize plain historical data for prediction. Inadequate use of temporal information has become a key problem in current forecasting. To address the problem, we must effectively analyze the influence of time periods while integrating the distinct characteristics of traffic flow across various time granularities. This paper proposed a multi-granularity temporal embedding Transformer network, namely MGTEFormer. An embedding input adeptly merges complex temporal embeddings, a temporal encoder to consolidate rich temporal information, and a spatial encoder to discern inherent spatial characteristics between different sensors. The combined embeddings are fed into the attention mechanism's encoder, culminating in prediction results obtained through a linear regression layer. Temporal embedding can help by fussing the period and various temporal granularities into plain historical traffic flow that can be learned adequately, reducing the loss of time information. Experimental analyses and ablation studies conducted on real traffic datasets consistently attest to the superior performance of the MGTEFormer. Our approach reduces the mean absolute error of the original models by less than 1.7%. Extensive experiments demonstrate the superiority of the proposed MGTEFormer over existing benchmarks.

In this study, CO 2 reacted with a curing agent through nucleophilic addition to form ammonium salts, enabling the stable capture and internal release of CO 2 , which achieved gas-phase nucleation and foaming. Additionally, the introduction of wave-absorbing agents improved the absorption mechanism and promoted uniform foaming. This nucleation-free foaming process relies on the induced growth of gas nuclei and the synergistic effect of the wave-absorbing agents, effectively preventing the uneven foaming issues caused by traditional nucleating agents. Ultimately, a lightweight epoxy foam absorbing material (LFAM) was developed. BET tests showed that 2.0 wt% carbon-based wave-absorbing agents (LFAMs-A2) expanded the material's volume to 4.6 times its original size, forming a uniform porous structure. VNA tests revealed that LFAMs-A2 achieved a minimum reflection loss of -13.25 dB and an absorption bandwidth of 3.7 GHz in the 12-18 GHz range. The material with 2.0 wt% ferrite-based wave-absorbing agents (LFAMs-C2) achieved a minimum reflection loss of -26.83 dB at 16.6 GHz and an absorption bandwidth of 5.3 GHz, nearly covering the Ku band. DSC tests indicated that the material maintained good thermal stability at 150 °C. This study provides a new approach for lightweight coatings and structural optimization, with broad application potential in 5G communications, microwave anechoic chambers, and aerospace fields.

In recent years, the rapid growth of video data posed challenges for storage and transmission. Video compression techniques provided a viable solution to this problem. In this study, we proposed a bidirectional coding video compression model named DeepBiVC, which was based on two-stage learning. Firstly, we conducted preprocessing on the video data by segmenting the video flow into groups of continuous image frames, with each group comprising five frames. Then, in the first stage, we developed an image compression module based on an invertible neural network (INN) model to compress the first and last frames of each group. In the second stage, we designed a video compression module that compressed the intermediate frames using bidirectional optical flow estimation. Experimental results indicated that DeepBiVC outperformed other state-of-the-art video compression methods regarding PSNR and MS-SSIM metrics. Specifically, on the VUG dataset at bpp = 0.3, DeepBiVC achieved a PSNR of 37.16 and an MS-SSIM of 0.98.

Flavonoids derived from plants in the citrus family can have an alleviating effect on allergic asthma. The aim of this study was to provide insights into the mechanisms by which these compounds exert their effects on allergic asthma by combining theoretical and practical approaches. Aurantii Fructus Immaturus flavonoids (AFIFs) were obtained by solvent extraction and were determined by high performance liquid chromatography (HPLC). In vivo and in vitro experiments combined with network pharmacology, Mendelian randomization (MR) analysis and the AutoDock method were applied to study the mechanism of their effects. The main AFIFs were found to be hesperidin (13.21 mg/g), neohesperidin (287.26 mg/g), naringin (322.56 mg/g), and narirutin (19.35 mg/g). Based on the network pharmacology and MR analysis results, five targets Caspase 3 (CASP3), CyclinD1 (CCND1), Intercellular adhesion molecule (ICAM), erb-b2 receptor tyrosine kinase 2 (ERBB2), and rubisco accumulation factor 1 (RAF1) were selected, and the interactions between the AFIFs and the targets were studied using AutoDock Vina. The results indicated that glycosidic bonds play an important role in the interactions between AFIFs and both ERBB2 and RAF1.

Conventional floating bridge systems used during emergency repairs, such as during wartime or after natural disasters, typically rely on passive rubber bearings or semi-active control systems. These methods often limit traffic speed, stability, and safety under dynamic conditions, including varying vehicle loads and fluctuating water levels. To address these challenges, this study proposes a novel Hydraulic Self-Adaptive Bearing System (HABS). The system integrates real-time position closed-loop control and a flexible support compensation method to enhance stability and adaptability to environmental changes. A modified three-variable controller is introduced to optimise load response, while a multi-state observer control strategy effectively reduces vibrations and improves traffic smoothness. A 1:15 scale prototype was constructed, and a co-simulation model combining MATLAB/Simulink and MSC Adams was developed to simulate various operational conditions. Results from both experiments and simulations demonstrate the HABS's ability to adapt to varying loads and environmental disturbances, achieving a 72% reduction in displacement and a 54% reduction in acceleration. These improvements enhance traffic speed, stability, and safety, making the system a promising solution for emergency and floating bridges, providing superior performance under challenging and dynamic conditions.

The epidermal growth factor receptor (EGFR) is frequently overexpressed in a variety of human epithelial tumors, and its aberrant activation plays a pivotal role in promoting tumor growth, invasion, and metastasis. The clinically approved passive EGFR-related therapies have numerous limitations. Seven EGFR-ECD epitope peptides (EG1-7) were selected through bioinformatics epitope prediction tools including NetMHCpan-4.1, NetMHCIIpan-3.2, and IEDB Consensus (v2.18 and v2.22) and fused to the translocation domain of diphtheria toxin (DTT). The A549 tumor model was successfully established in a murine mouse model. The vaccine was formulated by combining the adjuvants Alum and CpG and subsequently assessed for its immunogenicity and anti-tumor efficacy. DTT-EG (3;5;6;7) vaccines elicited specific humoral and cellular immune responses and effectively suppressed tumor growth in both prophylactic and therapeutic mouse tumor models. The selected epitopes EG3 (HGAVRFSNNPALCNV145-159), EG5 (KDSLSINATNIKHFK346-360), EG6 (VKEITGFLLIQAWPE398-412), and EG7 (LCYANTINWKKLFGT469-483) were incorporated into vaccines for active immunization, representing a promising strategy for the treatment of tumors with overexpressed epidermal growth factor receptor (EGFR). The vaccine design and fusion method employed in this study demonstrate a viable approach toward the development of cancer vaccines.

Wellbore instability caused by hydration during the development of shale gas reservoirs poses significant challenges to drilling engineering. In this study, a novel and environmentally friendly shale inhibitor, TIL-NH 2 , was synthesized via free radical polymerization using 1-vinylimidazole and N-(2-bromoethyl)-1,3-propanediamine dihydrobromide as the main raw materials. The molecular structure of TIL-NH 2 was characterized by infrared spectroscopy and nuclear magnetic resonance. Incorporating imidazole cations and amino bifunctional groups, TIL-NH 2 exhibits excellent inhibitory performance and environmental friendliness. Its performance was systematically evaluated through linear swelling tests, shale cuttings rolling recovery tests, permeability recovery experiments, and dynamic adsorption analyses. The results indicate the following: (1) At a concentration of 1.2 wt%, TIL-NH 2 reduced the linear swelling height of shale by 65.69%, significantly outperforming traditional inhibitors like KCl and NW-1. (2) Under conditions of 140 °C, the cuttings rolling recovery rate of TIL-NH 2 reached 88.12%, demonstrating excellent high-temperature resistance. (3) Permeability recovery experiments showed that at a concentration of 2.0 wt%, TIL-NH 2 achieved a permeability recovery rate of 90.58%, effectively mitigating formation damage. (4) Dynamic adsorption experiments indicated that at a concentration of 2.5 wt%, the adsorption capacity tended toward saturation, reaching 26.00 mg/g, demonstrating stable adsorption capability. Additionally, environmental friendliness evaluations revealed that TIL-NH 2 has a degradation rate exceeding 90% within 28 days, and its acute toxicity is significantly lower than that of traditional inhibitors like KCl (the LC 50 of TIL-NH 2 is 1080.3 mg/L, whereas KCl is only 385.4 mg/L). This research provides a high-efficiency and environmentally friendly new inhibitor for green drilling fluid systems in horizontal shale gas wells, offering important references for technological advancements in unconventional energy development.

Porcine circovirus 3 (PCV3) is a small non-enveloped circovirus associated with porcine dermatitis and nephropathy syndrome (PDNS). It has occurred worldwide and poses a serious threat to the pig industry. However, there is no commercially available vaccine. PCV3 capsid protein (Cap) is an ideal antigen candidate for serodiagnosis. Here, a novel fully automated chemiluminescence enzyme immunoassay (CLEIA) was developed to detect antibodies (Abs) to Cap in porcine serum. Recombinant PCV3 Cap, self-assembled into virus-like particles (VLPs), was produced using baculovirus and coupled to magnetic particles (Cap-MPs) as carriers. Combined with an alkaline phosphatase (AP)-adamantane (AMPPD) system, Cap-Abs can be rapidly measured on a fully automated chemiluminescence analyzer. Under optimal conditions, a cut-off value of 31,508 was determined, with a diagnostic sensitivity of 96.8% and specificity of 97.3%. No cross-reactivity was observed with PCV1 and PCV2 and other common porcine pathogens, and both intra-assay and inter-assay coefficients were less than 5% and 10%, respectively. Prepared Cap-MPs can be stored at 4 °C for more than 6 months. Importantly, this CLEIA had a good agreement of 95.19% with the commercially available kit, demonstrating excellent analytical sensitivity and significantly reduced operating time and labor. A serological survey was then conducted, and showed that PCV3 continues to spread widely in South China. In conclusion, our CLEIA provides time and labor-saving, and a reliable tool for PCV3 epidemiological surveillance.

Mulberry ( Morus spp.) is an economically significant plant in the production of silk through feeding leaves to silkworm larvae. Traditional silkworm rearing is heavily labor-intensive, particularly in leaf collection, which leads to low efficiency and impedes the development of sericulture. Here, to assess the feasibility and effectiveness of a novel low-pruning mulberry cultivar, ZJ1, in the silkworm rearing industry, a comprehensive investigation integrating physiological, proteomic, and metabolomic analyses was conducted in comparison with the traditionally high-pruning cultivar, N14. The low-pruning mulberry variety ZJ1 exhibited a notable increase in annual leaf yield of 43.94%, along with a significant enrichment of serine and isoleucine contents, in contrast to those of the high-pruning variety N14. Through iTRAQ proteomics and LC-MS/MS metabolomics analyses, a total of 561 reduced and 803 increased differentially expressed proteins (DEPs), as well as 332 differential expressed metabolites (DEMs) in positive ions and 192 DEMs in negative ions, were identified in the ZJ1 group relative to the N14 group, respectively. The observed features in amino acid profiles and the enrichment of the sucrose-related metabolic pathway provided interesting insights for future endeavors in mulberry variety improvement and the optimization of silkworm diet formulations. Collectively, the low-pruning cultivar ZJ1, characterized by its rapid growth, high leaf productivity, and suitability for mechanized operations, is expected to be an efficient substitute in improving the future sericultural industry, especially in urbanized and industrialized regions.

Serious electron leakage and poor hole injection efficiency are still challenges for deep ultraviolet AlGaN-based light-emitting diodes with a traditional structure in achieving high performance. Currently, the majority of research works concentrate on optimizing the structures of the electron blocking layer (EBL) and last quantum barrier (LQB) separately, rather than considering them as an integrated structure. Therefore, in this study, an Al-content-varied AlGaN composite last quantum barrier (CLQB) layer is proposed to replace the traditional EBL and LQB layers. It is found that when the Al content in the CLQB decreases from 70% to 60% along the growth direction, the sample's luminescence efficiency is improved, which can be ascribed to the higher carrier concentration in the multiple quantum well active region caused by suppressed electron leakage and enhanced hole injection. Additionally, in the CLQB structure, the carrier loss at the EBL/LQB hetero-interface, which is inevitable in the traditional structure, can be avoided. However, if the Al content in the CLQB changes in an opposite way, i.e., increasing from 60% to 70%, the device optoelectronic performance deteriorates, since the electron leakage is enhanced and the hole injection is suppressed.

Unlike other ubiquitin-like family members, UBL5 is structurally and functionally atypical, and a novel role in various biological processes and diseases has been discovered. UBL5 can stabilize the structure of the spliceosome, can promote post-transcriptional processing, and has been implicated in both DNA damage repair and protein unfolding reactions, as well as cellular mechanisms that are frequently exploited by viruses for their own proliferation during viral infections. In addition, UBL5 can inhibit viral infection by binding to the non-structural protein 3 of rice stripe virus and mediating its degradation. Therefore, UBL5 is an important link between viral infections and immunity, and its study will be beneficial for the prevention and treatment of viral infections in the future. However, a review of the current findings on the role of UBL5 in viral infection has not been undertaken. Therefore, in this review, we summarize the recent progress in understanding the functions of UBL5 and discuss its putative role in viral infections.