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Abstract Droplets impinging on sparse microgrooved polydimethylsiloxane (PDMS) surfaces with different solid fractions was experimentally investigated. First, wettability and stability of droplets on these surfaces was analyzed. The advancing and receding contact angles were found to have a large difference between in the longitudinal direction and in the transverse one, which could be attributed to the anisotropy of the micropatterned surfaces. The judgement of whether a droplet on a sparse microgrooved structure is collapsed or suspended is proposed, and it was found that the droplets were in the Cassie-Baxter wetting state when the actual contact line density is greater than the critical contact line density, while they were in the Wenzel wetting state otherwise. Second, for the case of droplets impacting on sparse microgrooved PDMS surfaces, it was found that droplets can bounce off the micro-patterned surface with a solid fraction of 0.158 when the impact velocity was in a certain range. The lower limit of impact velocity for bouncing droplets can be determined by balancing the kinetic energy of the droplets with the energy barrier due to contact angle hysteresis. The upper limit of impact velocity for bouncing droplets was predicted using a theoretical model taking into account the penetration of liquid into the cavities between microstripes.

This study evaluated the effects of selenium-enriched yeast (SY) supplementation at various levels on health and production parameters in laying hens, including egg production, egg quality, selenium (Se) concentrations in eggs, liver health, serum biochemical markers, antioxidant function, and immune responses. A total of 360 Hy-Line Brown hens (28 weeks old) were randomly assigned to four dietary groups with six replicates of 15 birds each, monitored over a 12-week feeding trial after a two-week acclimatization period. The dietary groups included a control (basal diet without selenium) and three SY-supplemented groups with Se levels of 0.3 mg/kg (SY03), 1.5 mg/kg (SY15), and 6.0 mg/kg (SY60). The results showed no significant effects of dietary SY on laying performance or feed efficiency (P > 0.05). However, the SY15 group showed significant improvements in egg quality, particularly in albumen height, Haugh Unit and yolk color (P < 0.05). Selenium concentrations in eggs, albumen, and yolk increased dose-dependently, with significant differences in the SY-supplemented groups (P < 0.001). Increased activities of liver enzymes including alanine transaminase, alkaline phosphatase, and aspartate transaminase, alongside elevated levels of uric acid were notable in the SY60 group (P < 0.05). In addition, histological analysis revealed significant hepatocyte degeneration and a higher liver organ index (P < 0.05), in the SY60 group. All of which suggests potential liver toxicity at higher selenium levels. Antioxidant capacity of the birds were significantly enhanced due to dietary supplementation of SY as indicated by increased serum levels of total antioxidant capacity, and activities of catalase, glutathione peroxidase, and superoxide dismutase (P < 0.05). Analysis of hepatic genes expression revealed that SY15 supplementation significantly upregulated key antioxidant-related genes (Nrf2, HO-1, CAT, and NQO1) and downregulated Keap1 expression (P < 0.05), suggesting strong activation of the antioxidant defense system. In conclusion, SY supplementation at 1.5 mg/kg improved egg quality, increased Se concentrations in eggs, and enhanced antioxidant capacity without affecting laying performance or liver health. This makes it a balanced approach to improving egg quality and poultry health. However, higher supplementation levels (6.0 mg/kg) resulted in liver damage, underscoring the importance of careful dosage consideration.

Abstract Background Actinobacillus pleuropneumoniae is a serious pathogen in pigs. The abundant application of antibiotics has resulted in the gradual emergence of drugresistant bacteria, which has seriously affected treatment of disease. To aid measures to prevent the emergence and spread of drug-resistant bacteria, herein, the kill rate and mutant selection window (MSW) of danofloxacin (DAN) against A. pleuropneumoniae were evaluated. Methods For the kill rate study, the minimum inhibitory concentration (MIC) was tested using the micro dilution broth method and time-killing curves of DAN against A. pleuropneumoniae grown in tryptic soy broth (TSB) at a series drug concentrations (from 0 to 64 MIC) were constructed. The relationships between the kill rate and drug concentrations were analyzed using a Sigmoid Emax model during different time periods. For the MSW study, the MIC99 (the lowest concentration that inhibited the growth of the bacteria by ≥ 99%) and mutant prevention concentration (MPC) of DAN against A. pleuropneumoniae were measured using the agar plate method. Then, a peristaltic pump infection model was established to simulate the dynamic changes of DAN concentrations in pig lungs. The changes in number and sensitivity of A. pleuropneumoniae were measured. The relationships between pharmacokinetic/pharmacodynamic parameters and the antibacterial effect were analyzed using the Sigmoid Emax model. Results In kill rate study, the MIC of DAN against A. pleuropneumoniae was 0.016 µg/mL. According to the kill rate, DAN exhibited concentration-dependent antibacterial activity against A. pleuropneumoniae. A bactericidal effect was observed when the DAN concentration reached 4–8 MIC. The kill rate increased constantly with the increase in DAN concentration, with a maximum value of 3.23 Log10 colony forming units (CFU)/mL/h during the 0–1 h period. When the drug concentration was in the middle part of the MSW, drugresistant bacteria might be induced. Therefore, the dosage should be avoided to produce a mean value of AUC24h/MIC99 (between 31.29 and 62.59 h. The values of AUC24h/MIC99 to achieve bacteriostatic, bactericidal, and eradication effects were 9.46, 25.14, and > 62.59 h, respectively. Conclusion These kill rate and MSW results will provide valuable guidance for the use of DAN to treat A. pleuropneumoniae infections.

ABSTRACT Canine parvovirus (CPV) can cause high morbidity and mortality rates in puppies, posing a significant threat to both pet dogs and the breeding industry. Rapid, accurate, and convenient detection methods are important for the early intervention and treatment of canine parvovirus. In this study, we propose a visual CPV detection system called nucleic acid mismatch enzyme digestion (NMED). This system combines loop-mediated isothermal amplification (LAMP), endonuclease for gene mismatch detection, and colloidal gold lateral chromatography. We demonstrated that NMED can induce the binding of the amplicon from the sample to the specific labeling probe, which in turn triggers digestion by the endonuclease. The sensitivity and visual visibility of LAMP were increased by combining endonuclease and colloidal gold lateral chromatography assisted by a simple temperature-controlled device. The sensitivity of the NMED assay was 1 copy/μL, which was consistent with quantitative PCR (qPCR). The method was validated with 20 clinical samples that potentially had CPV infection; 15 positive samples and 5 negative samples were evaluated; and the detection accuracy was consistent with that of qPCR. As a rapid, accurate, and convenient molecular diagnostic method, NMED has great potential for application in the field of pathogenic microorganism detection.IMPORTANCEThe NMED method has been established in the laboratory and used for CPV detection. The method has several advantages, including simple sampling, high sensitivity, intuitive results, and no requirement for expensive equipment. The establishment of this method has commercial potential and offers a novel approach and concept for the future development of clinical detection of pathogenic microorganisms.

Epoxy/glass fibre composites possess excellent mechanical and electrical properties and are widely utilised in electrical and electronic power equipment. However, the composites exhibit relatively poor thermal conductivity, causing the temperature of the composites to increase during the operation of power equipment, resulting in a significant reduction in the electrical breakdown strength. Although the effects of thermal aging on polymeric materials have been widely studied, its influence on electrical strength mechanisms has not been investigated at the molecular level. In this study, epoxy/glass fibre composite specimens were subjected to accelerated thermal aging treatment for 360 h at 180 °C. Functional groups, molecular chain dynamics, and electrical breakdown are characterised using infrared spectroscopy, dielectric spectroscopy, and breakdown measurement. Subsequently, electrical breakdown mechanism and life prediction of the thermally aged composites are discussed. During thermal aging, the epoxy resin molecular chains undergo continuous oxidation and chain scission, which generate numerous polar functional groups and short chains and an increase in the free volume. This triggers an enhancement in the chain segmental dynamics, thereby significantly reducing the activation energy of the epoxy resin. After 360 h, activation energy decreased from 0.78 eV to 0.67 eV. The DC breakdown voltages of the specimens decreased from 168.28 kV/mm to 134.91 kV/mm. An insulation life prediction model for thermally aged epoxy/glass fibre composites is established based on the time-temperature equivalence theory. The prediction results indicate that the service life of the operational composites is approximately 11.2 years at 353 K, which is consistent with engineering experience.

Chromium, being among the most toxic heavy metals, continues to demand immediate attention in the remediation of Cr-contaminated environments. In this study, a strain of LBA36 (Bacillus toyonensis) was isolated from heavy metal contaminated soil in Luanchuan County, Luoyang City, China. The reduction and adsorption rates of LBA36 in 30 mg·L−1 Cr-containing medium were 97.95% and 8.8%, respectively. The reduction mechanism was confirmed by Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy (XPS). Cr(VI) reduction by this strain predominantly occurred outside the cell, with hydroxyl, amide, carboxyl, C-N group, carbonyl, and sulfur carbonyl as the main reaction sites. XPS analysis revealed the presence of Cr2p1/2 and Cr2p3/2. Furthermore, the hydroponic experiment showed that the fresh weight and plant height of radish seedlings increased by 87.87% and 37.07%, respectively, after inoculation with LBA36 strain under 7 mg·L−1 Cr(VI) stress. The levels of chlorophyll, total protein, malondialdehyde, superoxide dismutase and catalase were also affected to different degrees. In conclusion, this study demonstrated the potential of microbial and phytoremediation in the treatment of heavy metal toxicity, and laid the foundation for the development of effective bioremediation methods for Cr(VI) pollution.

Abstract Owing to advanced power electronic and electrical applications developing towards miniaturisation and integration, the thickness‐dependent DC breakdown mechanism of epoxy/multiwall‐carbon‐nanotube nanocomposites is under investigation. The results indicate that the breakdown strength of nanocomposites containing 0.05 wt% multiwall‐carbon‐nanotubes rises by ∼18%, and the breakdown strength falls exponentially with increasing thickness. To clarify the microscopic mechanism, a simulation model of DC breakdown, including carriers transport and segmental dynamics, is developed, and the accordant simulation results with experimental results indicate that the thickness‐dependent DC breakdown of epoxy/multiwall‐carbon‐nanotube nanocomposites is determined both by segment chain dynamics and charge transport. According to the breakdown model analysis, the effects of multiwall‐carbon‐nanotube on enhanced breakdown strength are caused by the increased amount of deep traps in the interfacial region, while the influence of thickness is attributed to the enlarged segment chain displacement and electric field distortion as the voltage raising time increases.

To investigate the differences in seismic performance of buckling-restrained braces (BRBs) with significantly different lengths and to explore the influence of length on the energy dissipation efficiency of BRBs within the same structure, this study designed and fabricated two BRBs with lengths of 8.5 m and 3 m based on an actual engineering project. Low-cycle reciprocating load tests were conducted to compare the performance of the two BRBs in terms of hysteretic energy dissipation capacity, tension–compression bearing capacity imbalance coefficient, cumulative plastic deformation capacity, and low-cycle fatigue life. Additionally, the energy dissipation and damping efficiency of BRBs of different lengths within the same structure was analyzed. The results indicate that under cyclic loading based on design displacement, the 8.5 m BRB exhibits a greater equivalent viscous damping ratio, cumulative hysteretic energy dissipation, and cumulative plastic deformation, leading to more efficient energy dissipation and damping effects. The length of the brace is a significant factor affecting the imbalance coefficient of tension–compression bearing capacity, with longer braces resulting in a larger imbalance coefficient. The 3 m BRB shows less deviation from the mean values of various fatigue parameters, indicating more stable low-cycle fatigue performance. Within the same structure, shorter BRBs with larger design displacements achieve higher energy dissipation efficiency, allowing for more effective utilization of their energy dissipation capacity. This study’s conclusions provide valuable references for designers in the rational selection of BRBs of different lengths in actual engineering projects and offer preliminary insights into the energy dissipation efficiency of BRBs of varying lengths within a structure.

Erzhi Wan (EZW), a classic Traditional Chinese Medicine formula, has shown promise as a potential therapeutic option for Alzheimer's disease (AD), yet its mechanism remains elusive. Herein, we employed an integrative in-silico approach to investigate the active components and their mechanisms against AD. We screened four active components with blood-brain barrier permeabilities from TCMSP, along with 307 corresponding targets predicted by SwissTargetPrediction, PharmMapper, and TCMbank websites. Then, we retrieved 2260 AD-related targets from Genecards, OMIM, and NCBI databases. Furthermore, we constructed the protein-protein interaction (PPI) network of the intersected targets via the STRING database and performed the GO and KEGG enrichment analyses using the “clusterProfiler” R package. The results showed that the intersected targets were intimately related to the p53/PI3K/Akt signaling pathway, serotonergic synapse, and response to oxygen level. Subsequently, 25 core targets were found differentially expressed in brain regions by bioinformatics analyses of GEO datasets of clinical samples from the Alzdata database. The binding sites and stabilities between the active components and the core targets were investigated by the molecular docking approach using Autodock 4.2.6 software, followed by pocket detection and druggability assessment via the DoGSiteScorer server. The results showed that acacetin, β-sitosterol, and 3-O-acetyldammarenediol-II strongly interacted with the druggable pockets of AR, CASP8, POLB, and PREP. Eventually, the docking results were further cross-referenced with the literature research and validated by 100 ns of molecular dynamics simulations using GROMACS software. Binding free energies were calculated via MM/PBSA strategy combined with interaction entropy. The simulation results indicated stable bindings between four docking pairs including acacetin-AR, acacetin-CASP8, β-sitosterol-POLB, and 3-O-acetyldammarenediol–II–PREP. Overall, our study demonstrated a theoretical basis for how three active components of EZW confer efficacy against AD. It provides a promising reference for subsequent research regarding drug discoveries and clinical applications.

IntroductionActinobacillus pleuropneumoniae (APP) is a serious pathogen that affects the development of livestock breeding. Due to excessive use of antimicrobial drugs, many multidrug-resistant bacteria have emerged and spread, which have threatened the livestock industry. Therefore, we established a peristaltic pump infection model (PPIM) to evaluate the susceptibility change and pharmacokinetic/pharmacodynamic (PK/PD) integration of tulathromycin against APP during the mutant selection window (MSW) for preventing the emergence of mutant-resistant bacteria.MethodsThe 99% minimum inhibitory concentration (MIC99) and mutant prevention concentration (MPC) of tulathromycin against APP were measured using the agar-plate method. After the model of dynamic infection had been established based on tulathromycin data in lungs, different dosages were administered to make the drug concentrations located in different parts of the MSW. The population and sensitivity of APP were monitored. Tulathromycin concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Finally, a sigmoid Emax model was used to analyze the relationships between PK/PD parameters and antibacterial effects.Results and discussionThe values of MIC, MIC99, and MPC of tulathromycin against APP were 2, 1.4, and 44.8 μg/mL, respectively. The PPIM was stable. An elimination effect without regrowth was observed at 5.6 to 44.8 μg/mL (−4.48 to −7.05 Log10 CFU/mL, respectively). The MIC of APP increased 32-fold at 8 MIC99. AUC168 h/MIC99 had the best fit with the antibacterial effect (R2 = 0.9867). The AUC168 h/MIC99 required to achieve bacteriostatic, bactericidal, and clearance effects were 1.80, 87.42, and 198 h, respectively. Our results could provide guidance for the clinical application of tulathromycin to treat APP infection and avoid the generation of drug-resistant bacteria.

This contribution focuses on understanding the bedding effect of coal rocks under the Brazilian splitting test. First, multiple Brazilian splitting tests were performed on coal rocks with various bedding angles to systematically investigate the influence of stratification. Subsequently, numerical models with stratified structures were constructed, and a continuous–discontinuous numerical analysis method based on the cohesive zone model (CZM) was employed to conduct the corresponding numerical investigations. Results indicate that the load–displacement curves of coal rock specimens with different bedding angles can be classified into four stages: initial compaction stage, elastic deformation stage, crack rapid coalescence stage, and final destruction stage. With increase in the bedding angle, the failure patterns of coal rock specimens can be categorized into three groups: 1) stretching damage along bedding planes; 2) mixed tension and shear failure along the bedding planes and the coal matrix; and 3) stretching failure passing through the coal matrix. Furthermore, the tensile strength and cumulative acoustic emission (AE) energy–displacement relations are significantly influenced by the bedding angle. The numerical model can effectively predict the mechanical responses and fracture behavior of coal rock specimens, providing empirical parameters for the simulation of similar rock engineering.

Offline reinforcement learning uses pre-collected expert data or other empirical data to learn action strategies offline without interacting with the environment. Offline reinforcement learning is preferable to online reinforcement learning because it has lower interaction costs and trial-and-error risks. However, offline reinforcement learning often faces the issues of severe extrapolation errors and low sample utilization because the Q-value estimation errors cannot be corrected in time by interacting with the environment. To this end, this paper suggests an effective sampling strategy for offline reinforcement learning based on TD-error, using TD-error as the priority measure for priority sampling, and enhancing the sampling efficacy of offline reinforcement learning and addressing the issue of out-of-distribution error by using a combination of priority sampling and uniform sampling. Meanwhile, based on the use of the dual Q-value estimation network, this paper examines the performance of the algorithms corresponding to their time-difference error measures when determining the target network using three approaches, including the minimum, the maximum, and the convex combined of dual Q-value network, according to the various calculation techniques of the target network. Furthermore, to eliminate the training bias arising from preference sampling using priority sampling, this paper uses a significant sampling mechanism. By comparing with existing offline reinforcement learning research results combining sampling strategies on the D4RL baseline, the algorithm proposed shows better performance in terms of the final performance, data efficiency, and training stability. To confirm the contribution of each research point in the algorithm, two experiments were performed in the ablation experiment section of this study. Experiment 1 shows that the algorithm using the sampling method with a combination of uniform sampling and priority sampling outperforms the algorithm using uniform sampling alone and the algorithm using priority sampling alone in terms of sample utilization and strategy stability, while experiment 2 compares the effect on the performance of the algorithm based on the double Q-value estimation network produced by the double network of a maximum, minimum, and maximum-minimum convex combination of values based on the dual Q-value estimation network with a total of three different time-difference calculation methods on the performance of the algorithm. Experimental evidence shows that the algorithm in the research that uses the least amount of dual networks performs better overall and in terms of data utilization than the other two algorithms, but its strategy variance is higher. The approach described in this paper can be used in conjunction with any offline reinforcement learning method based on Q-value estimation. This approach has the advantages of stable performance, straightforward implementation, and high scalability, and it supports the use of reinforcement learning techniques in real-world settings.

A high degree of hydrolysis can reduce the allergenicity of milk, while lactic acid bacteria (LAB) fermentation can further enhance the antioxidant ability of enzymatic milk. LAB with a strong antioxidant ability was screened, and the effects of LAB on the bitterness, taste and flavor of enzymatic skim milk (ESM) with a high degree of hydrolysis were investigated in this paper, in addition to the response surface methodology optimized the conditions of the LAB fermentation of ESM. The results indicate that the skim milk hydrolyzed by Protamex has a higher degree of hydrolysis and lower bitterness. The scavenging rate of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical, the inhibition rate of hydroxyl radical (·OH) and the superoxide dismutase (SOD) activity of Lactiplantibacillus plantarum 16 and Lactococcus lactis subsp. lactis m16 are significantly higher than those of other strains (p < 0.05), while the improvement effect of L. plantarum 16 on the bitterness and flavor of ESM is better than that of L. lactis subsp. lactis m16. The fermented ESM has a strong antioxidant ability and low bitterness when the inoculum quantity of L. plantarum 16 is 5%, fermentation at 37 °C for 18 h and the pH of the ESM is 6.5, for which the DPPH free radical scavenging rate is 61.32%, the ·OH inhibition rate is 83.35%, the SOD activity rate is 14.58 and the sensory evaluation is 4.25. The contents of amino acids related to bitterness and antioxidants were reduced and increased, respectively. The ESM fermented by L. plantarum 16 has a good flavor, antioxidant ability and low bitterness.

Inner Mongolia has the largest sheep population among China’s provinces, resulting in the production of a substantial amount of sheep manure. If left untreated, this manure can contribute to environmental pollution. However, sheep manure serves a dual purpose: it can be both a pollutant and a valuable source of organic fertilizer. Consequently, there is an urgent need to address the environmental issues arising from manure accumulation and its unused status. In this paper, a viable solution is proposed: the conversion of manure into fertilizer through a composting unit incorporating high-temperature aerobic fermentation technology. This unit, tailored for small farms and individual farmers, integrates critical functions such as ventilation, heating, and turning. Additionally, it boasts excellent thermal insulation, enhancing composting efficiency and enabling precise control over fermentation conditions. This design mitigates heat loss and accelerates maturation, addressing common challenges in traditional composting. The design process encompassed both equipment construction and control systems, with a primary focus on compost fermentation and aeration heating. The components were carefully designed or selected based on theoretical analysis and subsequently validated using simulation software, including EDEM and Fluent. The control system seamlessly integrates a touch screen interface, PLC programming, and control circuits to manage air pumps and electric heaters in response to changes in temperature and oxygen concentration. Furthermore, it controls the motors during the recovery phase. A comprehensive performance evaluation was conducted, revealing notable improvements. Under artificially heated conditions, the maximum temperature of the compost increased by approximately 20 °C, the composting cycle was reduced by roughly 4 days, and the seed germination index (GI) rose by about 9% when compared to natural fermentation. Thus, this device significantly accelerates composting and improves fertilizer quality by increasing the decomposition rate.

Microalgae demonstrate significant efficacy in wastewater treatment. Anaerobic digestion effluent (ADE) is regarded as an underutilized resource, abundant in carbon, nitrogen, phosphorus, and other nutrients; however, the presence of inhibitory factors restricts microalgal growth, thereby preventing its direct treatment via microalgae. The purpose of this study was to dilute ADE using various dilution media and subsequently cultivate Chlorella sp. to identify optimal culture conditions that enhance microalgal biomass and water quality. The effects of various dilution conditions were assessed by evaluating the biomass, sedimentation properties, and nutrient removal efficiencies of microalgae. The results demonstrate that microalgal biomass increases as the dilution ratio increased. The microalgae biomass in the treatments diluted with simulated wastewater was significantly higher than that with deionized water, but their effluent quality failed to meet discharge standards. The treatment diluted with deionized water for 10 times exhibited abundant microbial biomass with strong antioxidant properties. The corresponding total phosphorus concentration in the effluent (6.96 mg/L) adhered to emission limits under the Livestock and Poultry Industry Pollutant Emission Standards (8 mg/L), while ammonia nitrogen concentration (90 mg/L) was near compliance (80 mg/L). The corresponding microbial biomass, with a sludge volume index (SVI30) of 72.72 mL/g, can be recovered economically and efficiently by simple precipitation. Its high protein (52.07%) and carbohydrate (27.05%) content, coupled with low ash (10.75%), makes it a promising candidate for animal feed and fermentation. This study will aid in understanding microalgal growth in unsterilized ADE and establish a theoretical foundation for cost-effective ADE purification and microalgal biomass production.

An experimental study was undertaken to investigate the problem of the substantial variability in water content in unrotted sheep dung, which leads to a lack of universality and practicality in calibrating its discrete element simulation parameters. The stacking angle was used as the response value in these experiments. The objective of this study was to establish precise simulation parameters for the composting process. A model for water content-stacking angle was established using the cylinder-lifting technique, resulting in a correlation value of 0.997. Utilizing the Hertz–Mindlin with JKR bonding model, three EDEM particle models were developed, each with distinct particle sizes, based on the particle size distribution of sheep dung. The JKR surface energy was determined using the Plackett–Burman test, the steepest-climbing test, and the Box–Behnken test using a set of 10 parameters. A subsequent study was conducted on the JKR surface energy, rolling friction factor, and static friction factor utilizing the Plackett–Burman test and Box–Behnken test. A parameter model for stacking angle–discrete elements was developed that achieved a p-value below 0.0001 and a relative inaccuracy of 3.46% or less. The regression model for the water content–discrete element parameter was derived by combining the water content–stacking angle model with the stacking angle–discrete element parameter model. Validation of this model was conducted using both the pumping plate technique and the hopper approach, resulting in a relative error of 4.89% or less. The findings demonstrate that the specific characteristics of sheep manure may be accurately anticipated by considering its water content. This approach offers a valid and universally applicable way of predicting the specific characteristics of sheep dung in the simulation of composting equipment.

The Inner Mongolia Autonomous Region, known for its famous Mongolian horses, faces significant environmental challenges due to the large-scale rearing of these animals, which produces a substantial amount of manure. If not managed effectively, this manure can lead to severe environmental pollution. The aim of this study was to investigate whether a small-scale intelligent aeration and heating composting system is effective in treating Mongolian horse manure, with the objective of enhancing composting efficiency and resource utilization to support sustainable agricultural development in the region. The equipment was utilized to treat a compost mixture of Mongolian horse manure and corn stover, allowing for an analysis of the changes in key indicators throughout the composting process. The results demonstrated that the equipment maintained high temperatures for up to eight days during the composting process, effectively inactivating pathogens and promoting the efficient decomposition of organic matter. The system also successfully controlled humidity to 12.7% and maintained oxygen concentration within the optimal range. Post-composting analysis revealed that the final compost contained 2.3% nitrogen, 1.3% phosphorus, and 1.2% potassium, with a pH of 6.4 and conductivity of approximately 5.2 mS/cm. Additionally, the carbon-to-nitrogen ratio decreased significantly from 27.3 to 15.9, indicating substantial organic matter degradation. Seed germination tests showed germination rates of 80%, 86%, and 75% for corn, mung bean, and wheat, respectively, with a final seed germination index of 104%. This study concluded that the small aeration and heating composting equipment is highly effective in treating Mongolian horse manure, producing high-quality organic fertilizers that significantly enhance soil fertility and demonstrate considerable potential for supporting sustainable agricultural practices and improving environmental management in the Inner Mongolia Autonomous Region.

Achieving crowd formation transformations has wide‐ranging applications in fields such as unmanned aerial vehicle formation control, crowd simulation, and large‐scale performances. However, planning trajectories for hundreds of agents is a challenging and tedious task. When modifying crowd formation change schemes, adjustments are typically required based on the style of formation change. Existing methods often involve manual adjustments at each crucial step, leading to a substantial amount of physical labor. Motivated by these challenges, this study introduces a novel generative adversarial network (GAN) for generating crowd formation transformations. The proposed GAN learns specific styles from a series of crowd formation transformation trajectories and can transform a new crowd with an arbitrary number of individuals into the same styles with minimal manual intervention. The model incorporates a space–time transformer module to aggregate spatiotemporal information for learning distinct styles of formation transformation. Furthermore, this article investigates the relationship between the distribution of training data and the length of trajectory sequences, providing insights into the preprocessing of training data.

Lymphocyte activation gene 3 (LAG-3) is a negative immune checkpoint and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. Fibrinogen-like protein 1 (FGL1) is a major LAG-3 functional ligand that is upregulated in various human cancers. LAG-3 positive T cells bind FGL1 expressed by cancer cells, which inhibits T-cell activation and cytokine secretion via indirect blocking of T cell receptor (TCR) signaling. High expression of LAG-3 and FGL1 in patients with solid tumors is associated with drug resistance and decreased survival in response to FDA-approved immune checkpoint inhibitors. Therefore, targeting the LAG-3/FGL1 pathway represents a promising therapeutic strategy to maximize the number of patients benefiting from checkpoint blockade therapy. However, there are no small molecules in existence that target LAG-3/FGL1 interaction. Herein, we report a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate the ability of small molecules to inhibit LAG-3/FGL1 interaction. We further demonstrate the implementation of the developed assay in screening chemical libraries of small molecules from the NCI Diversity Set VII, FDA-approved drugs, and a focused library of NF-κB modulators. This work will pave the way for drug discovery efforts focused on therapeutic targeting of LAG-3/FGL1 interaction using small molecules.

With the installation of rubber isolation bearings in the upper and lower ground layers, an isolated step-terrace structure was created. Considering the ultimate bearing capacity of the rubber bearing under tension as the critical condition, a comprehensive framework was established to evaluate the overturning failure mechanisms present in isolated step-terrace structures. The bound of nominal aspect ratio was identified as the principal control index within this framework, which incorporates critical parameters such as height ratio (α), width ratio (β), vertical tensile stiffness to compressive stiffness ratio (γ), seismic coefficient (k), and nominal vertical compressive stress (σ0) to provide a thorough analysis of the structural responses and potential failure scenarios. In order to further investigate this matter, a scaled model of an isolated step-terrace concrete frame structure featuring two dropped layers and a single span within an 8° seismic fortification zone was meticulously crafted at a 1:10 similarity ratio. Subsequently, a series of shaking table tests were conducted to analyze the structural response under seismic excitation. The findings indicate that: utilizing the bound of nominal aspect ratio as a metric to gauge the anti-overturning capacity of isolated step-terrace structures is a justified approach. In instances where the height ratio remains constant, the bound of nominal aspect ratio for both positive and negative overturning trended upward with an increase in the width ratio. Notably, the bound of nominal aspect ratio for positive overturning consistently registered lower values compared to that of the negative overturning, underscoring the heightened susceptibility of step-terrace structures to positive overturning. Moreover, in scenarios characterized by higher height and width ratios, the structural integrity remained unscathed by any overturning effects arising from insufficient tensile strength in rubber bearings. Furthermore, the bound of nominal aspect ratio exhibited an ascending trend as the seismic coefficient, nominal vertical compressive stress, and vertical tensile stiffness to compressive stiffness ratio decreased. The outcomes derived from the shaking table test not only confirm the impressive seismic performance of the structure, but also, by closely examining the instantaneous stress variations within the upper and lower isolation layers of the model, substantiate the existence of a positive overturning hazard in scenarios marked by higher seismic coefficients (k). This observation aligns seamlessly with the theoretical projections, thereby substantiating the efficacy of the structural overturning failure theory through direct empirical verification.

The Inner Mongolia Autonomous Region is a crucial area in China with a significant advantage in animal husbandry, particularly in cattle and sheep farming. However, the disposal of the large quantities of manure produced during farming has severely impacted the industry’s healthy development. Proper treatment of the manure can convert it into organic fertilizer beneficial to farmland; otherwise, it will cause substantial environmental pollution. This study focuses on existing composting equipment and addresses the issues of cattle and sheep manure mixture ratios and compost maturity evaluation. Through experiments on the mixture of cattle and sheep manure, the optimal ratio for converting cattle and sheep manure into organic fertilizer was determined. Additionally, a fuzzy mathematical evaluation model was employed, along with experimental data, to establish a comprehensive evaluation system for aerobic compost maturity based on multiple indicators, revealing the variation patterns of maturity levels under different mixture ratios. The test results revealed that the composting equipment effectively controls the composting process, shortens the composting cycle, ensures the complete decomposition of organic matter, and meets national standards for livestock and poultry manure treatment. Regarding temperature and humidity, oxygen concentration, seed germination rate, pH value, electrical conductivity (EC), nitrogen, phosphorus, potassium content, and carbon-to-nitrogen ratio, the mixed compost of cattle and sheep manure in various ratios met the relevant standards for agricultural application. Various ratios of organic fertilizers containing cattle and sheep manure significantly promoted the growth of maize, wheat, and mung bean crops. Specifically, the compost decomposition cycle was shortest when sheep and cattle dung were mixed at a ratio of 2:1, while it was longest for all cattle dung. Finally, a fuzzy mathematical comprehensive evaluation model was established by selecting four indicators: water content, carbon-to-nitrogen ratio, apparent score, and germination index. The study demonstrates that the equipment and method offer significant advantages in efficiently treating cattle and sheep manure and producing organic fertilizer, thereby providing strong support for the sustainable development of animal husbandry.

ObjectiveCell division cycle 42 (CDC42) regulates CD4+T-cell differentiation and participates in vascular stiffness and atherosclerosis and is involved in the progression of Stanford type B aortic dissection (TBAD). This study aimed to explore the correlation between serum CDC42 level and CD4+T cell subsets and in-hospital mortality in TBAD patients.MethodsSerum CDC42 and peripheral blood T-helper (Th) 1, Th2, and Th17 cells were detected in 127 TBAD patients by enzyme-linked immunosorbent assay and flow cytometry, respectively. Serum CDC42 was also quantified in 30 healthy controls.ResultsSerum CDC42 was decreased in TBAD patients vs. healthy controls (median [interquartile range (IQR)]: 418.0 (228.0–761.0) pg/ml vs. 992.0 (716.3–1,445.8) pg/ml, P

The determination of the low-temperature plasma propagation of SF6/N2 in gas discharge will accelerate the application of SF6/N2 in advanced electrical equipment. This study investigates the positive streamer propagation characteristics of SF6/N2 by establishing a plasma discharge model and discusses the effects of SF6 ratio on the electron density, electric field, chemical reaction rates, ion concentrations, and streamer thickness and velocity. As the streamer propagates, the shapes of the electron density and electric field become “narrower and taller.” Moreover, the ionization and attachment reaction rates increase, and the streamer thickness and velocity decrease with increasing SF6 mixing ratio and propagation time. As the SF6 ratio increases, the electric field distortion degree and particle mobility near the high-voltage electrode decrease due to the increase in the ionization and attachment rates. Consequently, the streamer velocity remains nearly unchanged, but the streamer thickness obviously decreases in the corona discharge process. In the streamer propagation process, the decrease in the streamer thickness and velocity with increasing SF6 ratio is attributed to the reduction in the electric field distortion and particle mobility, which stems from the increase in the DC breakdown voltage with the SF6 mixing ratio. The study results clarify the influence mechanisms of the SF6 mixing ratio on the particles’ spatiotemporal evolution during streamer propagation.

This study examines the widespread practice of upstream tailings dam construction in metallurgical mines in China, conducting comprehensive testing and research on tailings from various depositional zones of the Caijiagou tailings pond. Analysis of the test results from three types of tailings reveals a systematic relationship between the mechanical characteristics of tailings and their depositional zones: the farther from the dam, the finer the tailings particles, categorized as silty clay tailing, silt tailing, and sandy silt tailing. Consistent patterns were observed in the consolidated-drained shear strength and consolidated-undrained effective shear strength of these tailings. Among these, sandy silt tailing exhibited the highest strength, whereas silty clay tailing displayed the lowest. The dynamic stress–strain relationships of all three tailings types are described using the Hardin equivalent viscous-elastic model, where the initial dynamic shear modulus and the maximum dynamic shear stress in the model increased with effective confining pressure. The damping ratios exhibited a three-stage trend with increasing dynamic strain: gradual increase, rapid growth, and then gradual stabilization. Under various consolidated stress conditions, the ratio of the damping ratio to the maximum damping ratio versus the reduction in dynamic shear modulus showed a favorable linear relationship. Under vibration conditions, the dynamic shear stress corresponding to tailings failure increased with higher effective confining pressure and consolidated stress ratio. Finally, this study summarizes the parameters and indicators related to the saturated tailings of iron mines used in the research. Our work provides a foundation and reference for the design of tailings dams and the development and utilization of abandoned tailings ponds.

Loess has unique water sensitivity due to its distinct formation environment. The structure of loess is undercompactness, weak cementation, and porousness. The water sensitivity of loess directly leads to many environmental problems and geological hazards, including subgrade subsidences, slope collapse or failures, and building cracking. To reveal the relationship between water sensitivity and loess structure, confined-compression collapsibility tests and triaxial-collapsibility tests were performed on loess in different areas. The collapsibility coefficient, porosity ratio, and collapsibility rate were analyzed. Results show that the collapsibility process of loess can be divided into three stages: wetting, softening, and settling. The collapsibility sensitivity of loess is determined primarily by its structural and hydraulic state.

The Yumenkou Eastward-Expansion Water Pumping Project is an important pipeline for water network construction in Shanxi Province, China. This pipeline is vital for the development of cities and agricultural lands along its path. However, the foundation of the water delivery pipeline is mostly located in collapsible loess strata, thereby affecting project safety. To investigate the feasibility of foundation treatment schemes for the water delivery pipeline, a numerical analysis model is proposed in this study based on the analyzes of the leakage of water pipelines and different foundation treatment schemes through laboratory tests, field tests, and numerical simulations. Results show that the deeper the loess layer is, the smaller the collapsible deformation is and the greater the initial collapse pressure is. Furthermore, the deeper the buried pipeline is, the greater the collapsible deformation is after water leakage. A 0.5 m-thick lime-stabilized soil cushion layer is the most economically reasonable solution among the simulated scenarios. The collapsible deformation caused by pipeline leakage can be divided into three stages: start-up, development, and stabilization. Addressing the leakage point during the start-up stage is crucial. The proposed numerical analysis model can provide an important basis for similar engineering designs.

Abstract The ability of natural plants to treat chronic diseases is closely related to their antioxidant function. Lactic acid bacteria (LAB) fermentation is an effective way to improve the nutritional value, biological activity and flavor of food. This study investigated the pH, titratable acidity, total polysaccharide, total flavone, total saponin, total polyphenol, and antioxidant activity of the FH06 beverage before and after probiotic fermentation. Results: After fermentation, FH06 had lower contents of total polysaccharides, total flavonoids, total saponins and total polyphenols but higher titratable acidity. The antioxidant activity was tested by total antioxidant capacity (FRAP method) and DPPH· scavenging ability. The FRAP value significantly increased after fermentation (P

This study specifically focuses on the damping efficiency of a damped structure with additional viscous dampers. A two-layer steel frame structure with eight sets of viscous dampers is used to conduct a series of seismic simulation shaking table tests, including a non-damped structure without dampers and two damped structures with dampers placed at 1/2 and 1/6 of the beam span, respectively. By conducting these tests, the energy dissipation, force, and displacement of the damper, as well as the parameters of the structure such as floor displacement and acceleration, are obtained. The main damping efficiency indicators of the damped structure are calculated, including the additional damping ratio, inter-story displacement utilization rate, as well as the reduction rate of the vertex displacement and the base shear relative to the non-damped structure. The study shows that the viscous dampers exhibit full hysteresis loops and a strong energy dissipation capacity in the structure. The seismic response of the vertex displacement and base shear in the damped structure is significantly smaller than that in the non-damped structure. Under different seismic levels, including frequent earthquakes, occasional earthquakes, and rare earthquakes, the damping effect of the dampers placed at 1/2 of the beam span is significantly better than that placed at 1/6 of the beam span. For example, the additional damping ratio for the X-direction artificial wave REN is 19% and 11%, 20% and 13%, and 13% and 11%, respectively. The patterns for inter-story displacement utilization ratio, reduction rate of the vertex displacement, and reduction rate of the base shear are similar. The research findings strongly indicate that the damped structure with additional viscous dampers exhibits excellent damping efficiency. In future damping design, designers need to fully consider the placement of viscous dampers within the beam span.

When subjected to seismic activity, tall isolated buildings with a high aspect ratio are susceptible to overturning as a result of the failure of rubber isolation bearings under tension. In order to address this issue, a guided-rail tension device (GR) has been developed to enhance the tensile strength of rubber bearings. Furthermore, a novel guided-rail isolation rubber bearing (GR&RB) has been proposed as a potential solution. Quasi-static tests have been conducted to investigate the mechanical properties of the GR, as well as the GR&LNR600 and LNR600. Additionally, numerical finite element analysis has been employed to study the seismic response of the GR&RB under El Centro seismic action in a high-rise building with an aspect ratio of approximately 4. The experimental results suggest that the inclusion of GRs has a limited effect on the horizontal mechanical attributes of rubber isolation bearings. Nevertheless, it simultaneously enhances their tensile strength, demonstrating a significant augmentation of 4.23 times. Moreover, the mechanical behavior of the GR aligns with the Hook model. The numerical analysis suggests that the utilization of GR&RB can mitigate the tensile stress levels of rubber isolators. Furthermore, it is recommended to augment the elastic tensile stiffness of the GR while reducing the open value to enhance the tensile efficiency, with the potential to attain up to 75% efficiency in tensile performance.

Inappropriate application of antimicrobial agents can result in resistance by bacteria to drugs and changes in bacterial ecology. In particular, the emergence of multi-drug resistant bacteria seriously aff ects the antibacterial effi cacy of drugs, which threatens the health and lives of humans and animals. Pharmacokinetic/Pharmacodynamic (PK/PD) models can be used to analyze the relationship between PK and PD data and the antibacterial eff ect. PK/PD models provide valuable guidance for optimization of dosage regimens, development of new drugs, setting of susceptibility breakpoints, and analyses of resistant mutants. Th e main models of PK/PD integration are in vitro PK/PD, ex vivo PK/PD, and in vivo PK/PD. Each of these models has its own advantages and disadvantages. Hence, knowing how to choose the appropriate PK/PD model has a huge infl uence on obtaining accurate PK/PD data. In this review, we describe the commonly used PK/PD methods. In this way, we provide a reference for optimizing drug regimens and preventing and controlling drug-resistant bacterial infections.

The slope shape has a significant effect on the surface stress state of slope, and the stress state is closely related to the slope stability. The previous rainfall infiltration model only takes the slope with straight line shape into account, and did not include the slope with curve shape. Combining Mein-Larson infiltration model with slope shape function, the infiltration function of concave slope under rainfall is deduced. Combined with limit equilibrium analysis method, a calculation model of concave slope stability is proposed. At the same time, according to the idea of slope shape fitting and slope shape simplification, the actual slope is studied as concave slope and straight slope respectively. The results show that the infiltration depth of wetting front has a linear relationship with rainfall time, and the wetting front is paralleled to the slope at different rainfall time. When the actual slope is analyzed as a concave slope, the rainfall infiltration law is more in line with the actual situation; when the rainfall time is 10 days, the calculation result of the shallow slope model is 0.95, while the stability coefficients of the calculation model and the numerical simulation are 1.004 and 1.003 respectively, and the relative error is not more than 1%. Therefore, compared with the previous calculation model, this model not only takes the actual slope shape into account, but also has the characteristics of simple calculation and high reliability.

Cefquinome is a new generation cephalosporin that is effective in the treatment of mastitis in animals. In this study, we evaluated the associations between the specific pharmacokinetics and pharmacodynamics (PK/PD) of cefquinome and its antibacterial activity against Streptococcus agalactiae in a mouse model of mastitis. After a single intramammary dose of cefquinome (30, 60, 120, and 240 μg/mammary gland), the concentration of cefquinome in plasma was analysed by liquid chromatography with tandem mass spectrometry (HPLC/MS-MS). The PK parameters were calculated using a one-compartment first-order absorption model. Antibacterial activity was defined as the maximum change in the S. agalactiae population after each dose. An inhibitory sigmoid Emax model was used to evaluate the relationships between the PK/PD index values and antibacterial effects. The duration for which the concentration of the antibiotic (%T) remained above the minimum inhibitory concentration (MIC) was defined as the optimal PK/PD index for assessing antibacterial activity. The values of %T > MIC to reach 0.5-log10CFU/MG, 1-log10 CFU/MG and 2-log10 CFU/MG reductions were 31, 47, and 81%, respectively. When the PK/PD index %T > MIC of cefquinome was >81% in vivo, the density of the Streptococcus agalactiae was reduced by 2-log10. These findings provide a valuable understanding to optimise the dose regimens of cefquinome in the treatment of S. agalactiae infections.

IntroductionThe rapid emergence and widespread spread of multidrug-resistant bacteria is a serious threat to the health of humans and animals. The pharmacokinetic/pharmacodynamic (PK/PD) integration model based on mutant selection window (MSW) theory is an important method to optimize the dosage regimen to prevent the emergence and spread of drug-resistant bacteria. Actinobacillus pleuropneumoniae (AP) is a pathogen that can cause pleuropneumonia in pigs.MethodsWe employed an in vitro dynamic infection model (DIM) to study the prevention of drug-resistant mutations of danofloxacin against AP. A peristaltic pump was applied to establish an in vitro DIM to simulate the PK of danofloxacin in plasma, and to study the MSW of danofloxacin against AP. A peristaltic-pump in vitro infection model was established to simulate dynamic changes in the danofloxacin concentration in pig plasma. PK and PD data were obtained. Then, the relationship between PK/PD parameters and antibacterial activity was analyzed by the sigmoid Emax model.Results and discussionThe area under the curve during 24 h/ the minimum concentration that inhibits colony formation by 99% (AUC24h/MIC99) had the best-fitting relationship with antibacterial activity. The AUC24h/MIC99 values for a bacteriostatic effect, bactericidal effect, and eradication effect were 2.68, 33.67, and 71.58 h, respectively. We hope these results can provide valuable guidance when using danofloxacin to treat AP infection.

With the development of ultrahigh voltage transmission line construction in northwest China, an increasing number of overhead transmission lines are crossing the loess regions. Ensuring the stability of electricity transmission towers and mitigating the risk of collapse are crucial prerequisites for the construction of transmission lines. Taking the 750 kV demonstration electricity transmission line in Guanting–Lanzhou East as an example, representative loess samples were selected for compression and collapsing sensitivity tests. Four foundation treatment schemes were designed, and the wetting deformation characteristics were investigated through numerical simulation of the rainfall infiltration process. Corresponding optimisation schemes were proposed. The collapsing process was divided into four stages through laboratory collapsing tests. The relationship function between saturation and the Duncan–Chang model parameters of loess was established, which was introduced into the finite element model to consider the rainfall infiltration process. The analysis of the displacement field, and loess saturation field with time after rainfall infiltration for the four schemes showed that adding a lime-stabilised soil cushion layer and waterproof layer to the inclined column foundation had the best effect. Given that the design scheme needs to consider safety and economy, the thickness of the cushion layer was optimised, thereby reducing the use of lime-stabilised soil by 20%. Research findings provide meaningful guidance for the design of transmission tower foundations in loess areas.

The strength of loess in seasonal frozen soil areas decreases evidently due to the freeze-thaw cycle, which even leads to some engineering and geological problems. Fibre reinforcement is very effective in improving the mechanical properties of soil. Triaxial tests under different water contents, freezing temperatures, and number of freeze-thaw cycles were carried out for fibre-reinforced loess to study the ability of fibre reinforcement to improve the resistance of loess to freeze-thaw damage; scanning electron microscopy (SEM) was also conducted. The effects of freeze and thaw deterioration and reinforcement were discussed by comparing the strength parameters under different test conditions, and the influence mechanism of freezing temperature, number of freeze-thaw cycles, and reinforcement on loess strength was explained. Results show that a lower freezing temperature indicates a more evident decrease in strength after thawing. Under the action of the first five freeze-thaw cycles, the degree of decrease is more prominent. The fibre reinforcement can reduce the fragmentation of aggregates in loess, thereby effectively restraining the deterioration effect of loess during freeze-thaw cycles. Finally, the strength parameter prediction model under different freeze-thaw cycles of reinforced loess is established, thereby providing theoretical support for engineering application and numerical simulation of fibre-reinforced loess.

We aimed to develop an item bank of computerized adaptive testing for eating disorders (CAT-ED) in Chinese university students to increase measurement precision and improve test efficiency. A total of 1,025 Chinese undergraduate respondents answered a series of questions about eating disorders in a paper-pencil test. A total of 133 items from four well-validated Chinese-version scales of eating disorders were used to construct the item bank of CAT-ED with the following analysis. First, unidimensionality, model fit, local independence, item fit, discrimination and differential item functioning (DIF) were tested. Then, two simulation studies were applied to test the CAT-ED’s effectivity and rationality by calculating concurrent criterion-related validity, sensitivity and specificity. The final item bank comprised 77 items, which met the requirements of local independence, item fit, high discrimination and no differential item functioning in CAT. The mean number of administered items in CAT with the stopping rule fixed at SE ≤ 0.3 was 11 items. The obtained results showed that CAT-ED had acceptable reliability, validity, sensitivity and specificity.

The inverse design of the material for given target property is challenging for glasses due to their disordered non-prototypical structure. Wang and Zhang propose a data-driven property oriented inverse approach for design of glassy materials with desired functionalities.

Performance creative evaluation can be achieved through affective data, and the use of affective featuresto evaluate performance creative is a new research trend. This paper proposes a “Performance Creative—Multimodal Affective (PC-MulAff)” model based on the multimodal affective features for performance creative evaluation. The multimedia data acquisition equipment is used to collect the physiological data of the audience, including the multimodal affective data such as the facial expression, heart rate and eye movement. Calculate affective features of multimodal data combined with director annotation, and defined “Performance Creative—Affective Acceptance (PC-Acc)” based on multimodal affective features to evaluate the quality of performance creative. This paper verifies the PC-MulAff model on different performance data sets. The experimental results show that the PC-MulAff model shows high evaluation quality in different performance forms. In the creative evaluation of dance performance, the accuracy of the model is 7.44% and 13.95% higher than that of the single textual and single video evaluation.

BackgroundPresently, a comprehensive analysis of integrin subunit genes (ITGs) in bladder cancer (BLCA) is absent. This study endeavored to thoroughly analyze the utility of ITGs in BLCA through computer algorithm-based bioinformatics.MethodsBLCA-related materials were sourced from reputable databases, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). R software-based bioinformatics analyses included limma-differential expression analysis, survival-Cox analysis, glmnet-Least absolute shrinkage and selection operator (LASSO), clusterProfiler-functional annotation, and gsva-estimate-immune landscape analysis. The expression difference of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsAmong the 11 ITGs that were abnormally expressed in BLCA, ITGA7, ITGA5, and ITGB6 were categorized as the optimal variables for structuring the risk model. The high-risk subcategories were typified by brief survival, abysmal prognosis, prominent immune and stromal markers, and depressed tumor purity. The risk model was also an isolated indicator of the impact of clinical outcomes in BLCA patients. Moreover, the risk model, specifically the high-risk subcategory with inferior prognosis, became heavily interlinked with the immune-inflammatory response and smooth muscle contraction and relaxation.ConclusionThis study determined three ITGs with prognostic values (ITGA7, ITGA5, and ITGB6), composed a novel (ITG-associated) prognostic gene signature, and preliminarily probed the latent molecular mechanisms of the model.

Thrombomodulin (TM) is involved in the pathological process of atherosclerosis; however, the underlying mechanism remains unclear. Oxidised low-density lipoprotein (Ox-LDL; 100 μg/mL) was used to induce human vascular smooth muscle cells (HVSMCs) into a stable atherosclerotic cell model. The expression levels of miR-550a-3p and TM were detected by real-time reverse transcription-polymerase chain reaction. Cell proliferation was estimated using CCK8 and EDU assays. Wound scratch and transwell assays were used to measure the ability of cells to invade and migrate. Propidium iodide fluorescence-activated cell sorting was used to detect apoptosis and cell cycle changes. A dual-luciferase reporter assay was performed to determine the binding of miR-550a-3p to TM. Our results suggested the successful development of a cellular atherosclerosis model. Our data revealed that TM overexpression significantly promoted the proliferation, invasion, migration, and apoptosis of HVSMCs as well as cell cycle changes. Upregulation of miR-550a-3p inhibited the growth and metastasis of HVSMCs. Furthermore, miR-550a-3p was confirmed to be a direct target of TM. Restoration of miR-550a-3p expression rescued the effects of TM overexpression. Thus, miR-550a-3p might play a role in atherosclerosis and, for the first time, normalised the function of injured vascular endothelial cells by simultaneous transfection of TM and miR-550a-3p. These results suggest that the miR-550a-3p/TM axis is a potential therapeutic target for atherosclerosis.

Abstract The elementary excitations in metallic glasses (MGs), i.e., β processes that involve hopping between nearby sub-basins, underlie many unusual properties of the amorphous alloys. A high-efficacy prediction of the propensity for those activated processes from solely the atomic positions, however, has remained a daunting challenge. Recently, employing well-designed site environment descriptors and machine learning (ML), notable progress has been made in predicting the propensity for stress-activated β processes (i.e., shear transformations) from the static structure. However, the complex tensorial stress field and direction-dependent activation could induce non-trivial noises in the data, limiting the accuracy of the structure-property mapping learned. Here, we focus on the thermally activated elementary excitations and generate high-quality data in several Cu-Zr MGs, allowing quantitative mapping of the potential energy landscape. After fingerprinting the atomic environment with short- and medium-range interstice distribution, ML can identify the atoms with strong resistance or high compliance to thermal activation, at a high accuracy over ML models for stress-driven activation events. Interestingly, a quantitative “between-task” transferring test reveals that our learnt model can also generalize to predict the propensity of shear transformation. Our dataset is potentially useful for benchmarking future ML models on structure-property relationships in MGs.

Pharmacokinetic/pharmacodynamic (PK/PD) integration models are used to investigate the antimicrobial activity characteristics of drugs targeting pathogenic bacteria through comprehensive analysis of the interactions between PK and PD parameters. PK/PD models have been widely applied in the development of new drugs, optimization of the dosage regimen, and prevention and treatment of drug-resistant bacteria. In PK/PD analysis, minimal inhibitory concentration (MIC) is the most commonly applied PD parameter. However, accurately determining MIC is challenging and this can influence the therapeutic effect. Therefore, it is necessary to optimize PD indices to generate more rational results. Researchers have attempted to optimize PD parameters using mutant prevention concentration (MPC)-based PK/PD models, multiple PD parameter-based PK/PD models, kill rate-based PK/PD models, and others. In this review, we discuss progress on PD parameters for PK/PD models to provide a valuable reference for drug development, determining the dosage regimen, and preventing drug-resistant mutations.

We wished to study the detailed and precise antibacterial activity of cefquinome against Actinobacillus pleuropneumoniae (APP) in vitro and ex vivo. We analyzed the relationships between kill rate and cefquinome concentration in broth and between pharmacokinetic/pharmacodynamic (PK/PD) parameters and antibacterial effect in serum and tissue cage fluid (TCF) of piglets. Cefquinome exhibited time-dependent antibacterial activity against APP according to the kill rate. The maximum kill rate was 0.48 log10 CFU/mL/h at the 0-9-h period in broth. In the ex vivo PK/PD study, the maximum concentration (Cmax), time to reach the maximum concentration (Tmax), terminal half-life (T1/2β), and area under the concentration time curve (AUCinfinity) were 5.65 μg/ml, 0.58 h, 2.24 h, and 18.48 μg·h/ml in serum and 1.13 μg/ml, 2.60 h, 12.22 h, and 20.83 μg·h/ml in TCF, respectively. The values of area under the curve during 24 h/minimum inhibitory concentration (AUC24h/MIC) for bacteriostatic, bactericidal, and bacterial eradication effects were 18.94, 246.8, and 1013.23 h in serum and 4.20, 65.81, and 391.35 h in TCF, respectively. Our findings will provide a valuable basis for optimization of dosage regimens when applying cefquinome to treat APP infection.

Slate with inherently transverse isotropy is abundant in metamorphic rock, in buildings, and in geotechnical engineering worldwide; the tensile and shear fracture behavior of layered slate is vital to know for engineering applications. In this paper, the Brazilian and semi-circular bend (SCB) tests of layered slate were performed. The fracture characteristics of the slate were investigated by numerical simulations developed by the hybrid finite and cohesive element method (FCEM). Results showed that the measured experimental tensile strength, and mode I fracture toughness of layered slate all showed a typical V-type trend as the bedding angle increased from 0° to 90°, and with divider type. The developed empirical relationship between tensile fracture toughness and tensile strength KIC = 0.094σt + 0.036 fitted experimentally and strongly correlated. The mechanical response and fracture patterns predicted by FCEM agreed well with those of the laboratory experiments. Moreover, the shear fracture behavior and mode II fracture toughness of the layered slate were explored by systematic numerical simulations. Research results provide potential insights for further prediction and improvement of the complex fracture behavior of anisotropic rock masses for rock engineering.

Objective: To explore the characteristics of metabolites in Shenheling (SHL) fermented by Lactobacillus fermentum. Methods: In this study, ultrahigh-performance liquid chromatography-quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-QE-MS) was used to qualitatively, quantitatively, and differentially analyze the metabolites of SHL before and after fermentation. Results: A total of 102 significant differential metabolites in nine categories were analyzed before and after fermentation. It mainly includes 29 terpenoids, 17 alkaloids, 14 organic acids and derivatives, 10 flavonoids, 9 phenylpropanoids, 6 phenols, 3 aromaticity, and 3 amino acid derivatives. Further screening found that the content of most active substances, such as alkaloids, organic acids, and flavonoids, increased significantly. These metabolites play an important role in improving the taste and efficacy of SHL. After fermentation, the contents of differential metabolites, such as panaquinquecol 2, ginsenoside Rh3, ginsenoside Rg3, dehydronuciferin, nicotinic acid, 5-hydroxytryptophan, azelaic acid, dihydrokaempferol, and chrysin, were increased, which increased the effects of antioxidation, anti-obesity, hypoglycemic, antibacterial, and improved immunity compared with those before fermentation. KEGG pathway analysis identified 10 metabolic pathways. Isoquinoline alkaloid biosynthesis, vitamin B6 metabolism, beta-alanine metabolism, nicotinate, and nicotinamide metabolism, purine metabolism, pantothenate and CoA biosynthesis, glyoxylate and dicarboxylate metabolism, tyrosine metabolism, citrate cycle (TCA cycle), phenylpropanoid biosynthesis, etc. Conclusions: Fermentation significantly changed the metabolites in SHL and played an important role in improving its taste, aroma quality, antioxidant, anti-obesity, and other health care functional components.

Intestinal colonization is beneficial to the role of probiotics, and prebiotics can promote the adhesion and colonization of probiotics in the intestine. This study optimized the combination of complex prebiotics that could improve the growth ability and adhesion ability of Limosilactobacillus fermentum (L. fermentum) DALI02 to Caco-2 cells in vitro and determined the effect of its colonization quantity and colonization time in the immunocompromised rat model. The results showed that all five prebiotics (fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), inulin, stachyose, and xylo-oligosaccharides (XOS)) significantly promoted the growth and adhesion of L. fermentum DALI02. It was found that 0.5% (w/w) inulin had the best growth promotion effect, and 0.5% FOS had the strongest adhesion promotion (the adhesion rate was increase by 1.75 times). In addition, 0.05% FOS, 0.20% GOS, 0.30% inulin, 0.20% stachyose, and 0.30% XOS could significantly improve the adhesion rate of L. fermentum DALI02 from 1.72% to 3.98%. After 1 w of intervention, the quantity of colonization in the fermented broth with prebiotics group was significantly higher than that in the fermented broth group. The intervention time was extended from 1 d to 4 w, and the amount of colonization of L. fermentum DALI02 in the fermented broth with prebiotics group increased significantly from 4.32 lgcopies/g to 5.12 lgcopies/g. After the intervention, the serum levels of lipopolysaccharide (LPS) and D-lactic acid in rats were significantly reduced, and the most significant was in the fermented broth with prebiotics group, with LPS and D-lactic acid levels of 74.11 pg/mL and 40.33 μmol/L, respectively. Complex prebiotics can promote the growth and adhesion of L. fermentum DALI02 and significantly increase the quantity of colonization and residence time of the strain in the intestine, which helps the restoration of intestinal barrier function and other probiotic effects.

C6F12O has the potential to be used in gas-insulated equipment because of its excellent insulation performance and low global warming potential value. In order to study the effect of O2 on the decomposition characteristics of the C6F12O/CO2 gas mixture, power frequency breakdown experiments were conducted on a C6F12O/O2/CO2 gas mixture with different O2 mixing ratios. The decomposition products of the C6F12O gas mixture after multiple breakdowns were analyzed qualitatively and quantitatively by gas chromatography-mass spectrometry. The effects of the O2 mixing ratio, breakdown times, and effective gas production rate on the decomposition characteristics of the gas mixture were investigated. The results show that the main decomposition products are CF4, C2F6, C3F6, C3F8, C4F10, C5F12, C3F7H, and CF2O, and the addition of O2 will promote the formation of the above several decomposition products. Except for C3F6, the concentrations of other decomposition products tend to increase and then decrease with the increase in the O2 mixing ratio. The concentrations of CF4, C2F6, C3F6, and C3F8 increase with the times of breakdowns. The effective gas production rates of CF4, C2F6, and C3F8 show a trend of increasing and then decreasing in the process of adding O2 to the C6F12O/O2/CO2 gas mixture. This study provides a reference for the industrial application of the C6F12O/O2/CO2 gas mixture.

To explore the modulating effect of Limosilactobacillus fermentum (L. fermentum) grx08 on anti-oxidative stress in the liver, heart, and kidney of high-fat diet in rats, a low-fat diet as a control and a high-fat diet was used to induce oxidative stress injury in rats. L. fermentum grx08 and its heat-inactivated bacteria were used to intervene. The results showed that the high-fat diet had caused oxidative stress injury in the liver, heart, and kidney of rats. L. fermentum grx08 significantly reduced the serum levels of liver, heart, and kidney injury markers (ALT, AST, LDH, CK-MB, UA, and Crea), while restoring the balance of lipid metabolism in the liver. It also enhanced the activity of antioxidant enzymes such as GSH-Px in the liver, heart, and kidney, scavenging NO radicals and reducing the content of MDA, a product of lipid peroxidation, which can regulate the anti-oxidative stress capacity of the liver, heart, and kidney to varying degrees. Among them, L. fermentum grx08 showed better modulating effect on kidney anti-oxidative stress, followed by liver, and the weakest modulating effect on heart. At the same time, L. fermentum grx08 heat-inactivated bacteria also had a partial modulatory effect as well as a similar effect profile to that of live bacteria.

This study aimed to explore the application of microdialysis in pharmacokinetic (PK)/pharmacodynamic (PD) integration of cefquinome against Actinobacillus pleuropneumoniae. After the A. pleuropneumoniae population reached 106 CFU/thigh, the mice received 0.04, 0.16, 0.63, 2.5, and 10 mg/kg cefquinome by subcutaneous injection. Plasma samples were collected by retro-orbital puncture for 4 h, and thigh dialysate was obtained by microdialysis at a flow rate of 1.5 μL/min for 6 h for the PK study. For the PD experiment, the infected mice were treated with a 4-fold-increase in the total cefquinome dose, ranging from 0.01 to 10 mg/kg/24 h, divided into one, two, three, four, and eight doses. The number of bacteria was determined and an inhibitory sigmoid maximum effect (Emax) model was used to analyse the relationships between PK/PD parameters and efficacy. The mean penetration of cefquinome from plasma to the thigh was 0.591. The PK data for PK/PD integration were obtained by extrapolation. The fittest PK/PD parameter for efficacy evaluation was %fT>MIC (the percentage of time that free drug concentrations exceed the MIC). The magnitudes of %fT>MIC to achieve net bacterial stasis, 1-log10 CFU reduction, 2-log10 CFU reduction, and 3-log10 CFU reduction were 19.56, 28.65, 41.59, and 67.07 % in plasma and 21.74, 36.11, 52.96, and 82.68% in murine thigh, respectively. Microdialysis was first applied to evaluate the PK/PD integration of cefquinome against A. pleuropneumoniae. These results would provide valuable references when we apply microdialysis to study the PK/PD integration model and use cefquinome to treat animal diseases caused by A. pleuropneumoniae.

This paper describes a study on the interaction between joint fissures in a nonpersistent jointed rock mass by introducing a self-consistent methodology, amending the traditional method of self-consistency by increasing the number of joints one by one, and deducing a new compound mesoscale and macroscale constitutive damage model based on the Betti energy reciprocity theorem. By analyzing the Mohr–Coulomb failure criterion and generalized von Mises yield criterion and their impact on the calculation result of macroscopic damage, the generalized von Mises criterion is proven to be more appropriate, and it is, thus, chosen for this compound damage constitutive model. Comparing the theoretical calculation and laboratory results of the compound damage model with the existing theoretical calculation results indicates the following: 1. The compound damage model in this paper provides a better fit of the stress–strain curves from the laboratory tests. 2. The theoretical calculative results for the compound damage model in this paper are consistent with the experimental results; that is, the peak load decreases as the connectivity rate increases. 3. For different joint angles and connectivity rates, the overall absolute deviations and relative deviations of the peak stress from the theoretical calculations and the laboratory tests are less than those from the theoretical calculations provided in the original literature. The theoretical calculations of the compound damage model in this paper are more aligned with the experimental results, verifying its correctness and rationality.