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Colon cancer is a common and lethal malignancy, ranking second in global cancer-related mortality, highlighting the urgent need for novel targeted therapies. The sea cucumber (Apostichopus japonicus) is a marine organism known for its medicinal properties. After conducting a bioinformatics analysis of the cDNA library of Apostichopus japonicus, we found and cloned a cDNA sequence encoding histidine-rich peptides, and the recombinant peptide was named rAj-HRP. Human histidine-rich peptides are known for their anti-cancer properties, raising questions as to whether rAj-HRP might exhibit similar effects. To investigate whether rAj-HRP can inhibit colon cancer, we used human colon cancer HCT116 cells as a model and studied the tumor suppressive activity in vitro and in vivo. The results showed that rAj-HRP inhibited HCT116 cell proliferation, migration, and adhesion to extracellular matrix (ECM) proteins in vitro. It also disrupted the cytoskeleton and induced apoptosis in these cells. In vivo, rAj-HRP significantly inhibited the growth of HCT116 tumors in BALB/c mice, reducing tumor volume and weight without affecting the body weight of the tumor-bearing mice. Western blot analysis showed that rAj-HRP inhibited HCT116 cell proliferation and induced apoptosis by upregulating BAX and promoting PARP zymogen degradation. Additionally, rAj-HRP inhibited HCT116 cell adhesion and migration by reducing MMP2 levels. Further research showed that rAj-HRP downregulated EGFR expression in HCT116 cells and inhibited key downstream molecules, including AKT, P-AKT, PLCγ, P38 MAPK, and c-Jun. In conclusion, rAj-HRP exhibits significant inhibitory effects on HCT116 cells in both in vitro and in vivo, primarily through the EGFR and apoptosis pathways. These findings suggest that rAj-HRP has the potential as a novel targeted therapy for colon cancer.

Background and Objectives: The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab are recently developed promising drugs used for treatment of familial hypercholesterolemia (FH). This systematic review and meta-analysis aimed to thoroughly evaluate the efficacy and safety of evolocumab and alirocumab among pediatric patients with FH. Materials and Methods: A comprehensive search was conducted in PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov from inception through July 2024 to identify primary interventional studies among pediatric patients with FH. Meta-analyses were performed if appropriate. Statistics were analyzed using Review Manager version 5.4 and Stata version 16.0. Results: Fourteen articles reporting nine unique studies were included. There were three randomized controlled trials (RCTs) assessing evolocumab or alirocumab involving a total of 320 pediatric patients, one cross-over trial and five single-arm or observational studies. Pooled results showed significant efficacy of evolocumab/alirocumab in reducing low-density lipoprotein cholesterol (LDL-C) (weighted mean difference [WMD]: −37.92%, 95% confidence interval [CI]: −43.06% to −32.78%; I2 = 0.0%, p = 0.60), apolipoprotein B (WMD: −33.67%, 95% CI: −38.12% to −29.22%; I2 = 0.0%, p = 0.71), and also lipoprotein(a) (WMD: −16.94%, 95% CI: −26.20% to −7.69%; I2 = 0.0%, p = 0.71) among pediatric patients with FH. The efficacies of evolocumab/alirocumab on LDL-C reduction within pediatric patients with heterozygous FH (HeFH) were consistent between studies, whereas in patients with homozygous FH (HoFH), it varied dramatically. Pediatric patients with the null/null variant may respond to the treatment. PCSK9 inhibitors were generally well tolerated within most pediatric patients, in line with previous studies among adult populations. Conclusions: The PCSK9 inhibitors evolocumab/alirocumab significantly reduced LDL-C and some other lipid parameters, such as apolipoprotein B, in pediatric patients with HeFH. These drugs may be appropriate as a potential therapy for pediatric patients with HoFH who cannot achieve LDL-C targets with other treatments. Evolocumab/alirocumab was generally well tolerated in the pediatric population.

Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein–protein interaction network screened out several hub proteins, including SRSF1/2/6/7/11, SF3B1/2, NOP14/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death.

A unidirectional link is typically incorporated into the DC input side of an inverter to ensure the reliability and stability of the microgrid power supply. Due to impedance and control variations among inverters, circulating currents may rapidly arise during the operation of parallel transient inverters. Nonetheless, the unidirectional power circulating in a DC unidirectional link results in energy accumulation on the DC side, causing DC bus voltage pumping and affecting MGs’ operation safety and stability. This paper proposes a non-communication-based circulation suppression strategy to suppress power circulation in parallel transients based on the local information of inverters. First, a parallel transient is modeled, and the power circulation phenomenon and its influencing factors are analyzed. Then, the instantaneous power and absorbed active energy are calculated to adjust the phase of the inverter output voltage and suppress power circulation. Moreover, the output frequency is adjusted to balance the DC-side voltage of each inverter. Then, the stability of the parallel system after adding the circulation suppression control strategy is verified using the Lyapunov function method. Finally, simulation and experimental results verify the effectiveness of the proposed power circulation suppression strategy.

The steelmaking–continuous casting process (SCCP) is a complex manufacturing process which exhibits the distinct features of process manufacturing. The SCCP involves a variety of production elements, such as multiple process routes, a wide array of smelting and auxiliary devices, and a variety of raw and auxiliary materials. The production-simulation of SCCP holds a natural advantage in being able to accurately depict the intricate production behavior involved, and this serves as a crucial tool for optimizing the production operation of the SCCP. This paper thoroughly considers the various production elements involved in the SCCP, such as the fluctuation of the converter smelting cycle, fluctuation of heat weight, and ladle operation. Based on the Plant Simulation software platform, a dynamic simulation model of the SCCP is established and detailed descriptions are provided regarding the design of an SCCP using dynamic-operation rules. Additionally, a dynamic operational control program for the SCCP is developed using the SimTalk language, one which ensures the continuous operation of the caster in the SCCP, using the discrete simulation platform. The effectiveness of the proposed dynamic simulation model is verified by the total completion time of the production plan, the transfer time of the heat among the different processes, and the frequency of ladle turnover. The simulation’s results indicate that the dynamic simulation model has a satisfactory effect in simulating the actual production process. On this basis, the application effects of different schedules are compared and analyzed. Compared with a heuristic schedule, the optimized schedule based on the “furnace–machine coordinating” mode reduces the weighted value of total completion time by 8.7 min, reduces the weighted value of transfer waiting time by 45.5 min, and the number of rescheduling times is also reduced, demonstrating a better application effect and verifying the optimizing effect of the “furnace–machine coordinating” mode on the schedule.

Glycation Stress (GS), induced by advanced glycation end-products (AGEs), significantly impacts aging processes. This study introduces a new model of GS of Caenorhabditis elegans by feeding them Escherichia coli OP50 cultured in a glucose-enriched medium, which better simulates human dietary glycation compared to previous single protein–glucose cross-linking methods. Utilizing WormCNN, a deep learning model, we assessed the health status and calculated the Healthy Aging Index (HAI) of worms with or without GS. Our results demonstrated accelerated aging in the GS group, evidenced by increased autofluorescence and altered gene expression of key aging regulators, daf-2 and daf-16. Additionally, we observed elevated pharyngeal pumping rates in AGEs-fed worms, suggesting an addictive response similar to human dietary patterns. This study highlights the profound effects of GS on worm aging and underscores the critical role of computer vision in accurately assessing health status and aiding in the establishment of disease models. The findings provide insights into glycation-induced aging and offer a comprehensive approach to studying the effects of dietary glycation on aging processes.

Excessive reactive oxygen species (ROS) may lead to oxidative damage and metabolic disorder. The pathogenesis of human bowel inflammation is closely related to oxidative damage of intestinal epithelial cells caused by ROS. This study aimed to explore the high-value utilization of the byproducts of sea cucumber in antioxidant food for colitis prevention. The technology of protease hydrolysis combined with Cordyceps militaris fermentation was used to obtain fermented sea cucumber viscera protease hydrolysates (FSVHs). The results revealed that FSVH could enhance antioxidant capacity and alleviate oxidative damage and apoptosis by activating the Nrf2/HO-1 pathway and triggering the self-protection immune mechanisms. Moreover, the FSVH supplementation could upregulate antioxidant-related metabolic pathways of Caco-2 cells such as glutathione metabolism, confirming the enhanced antioxidant capacity of damaged cells. In summary, FSVH could exert protective effects on Caco-2 cells in response to oxidative damage, providing a promising prospect for sea cucumber resource utilization and colitis prevention.

This research tackles the challenge of ice-induced vibrations in fixed-bottom offshore wind turbines, particularly the risk of frequency lock-in (FLI), a critical loading condition arising from slow ice movement against structures. We introduce an innovative FLI analysis process grounded in the ductile damage–collapse (DDC) mechanism, which offers a more accurate and significantly lower probability of FLI occurrence than conventional methods. Through dynamic evaluations employing a time-domain ice load model and FLI displacement analyses, we demonstrate that FLI can lead to higher structural vibrations than those caused by continuous brittle ice crushing. A case study of a 5 MW monopile wind turbine tower utilising Abaqus confirms the necessity for incorporating FLI considerations into structural design to ensure safety and performance in ice-prone environments. Comparing the DDC mechanism with the ISO method, our study reveals that the DDC approach predicts higher displacement and acceleration values during FLI, nearly an order of magnitude greater than those induced by ice loads with a 50-year return period. The research underscores the importance of robust ice-load integration in design strategies for offshore wind turbines, especially in regions susceptible to ice. It highlights the DDC mechanism as a novel strategy for enhancing structural resilience against ice-induced hazards.

Hydrogel-based devices commonly have a high demand for material durability when subjected to prolonged or cyclic loads. To extend their service life, it is crucial to have a deep understanding of the fatigue mechanisms of hydrogels. It is well-known that double-network (DN) hydrogels are characterized by high strength and toughness and are thus recognized as a promising candidate under load-bearing conditions. However, the existing studies in the literature mainly focus on their resistant capability to fatigue crack growth, while the underlying mechanisms of fatigue crack nucleation are still inconclusive. This work aims to bridge this knowledge gap by formulating a fatigue life predictor for DN hydrogels within the framework of configurational mechanics to elucidate the underlying mechanisms governing fatigue crack nucleation. The fatigue life predictor for DN hydrogels is derived from the configurational stress by incorporating the corresponding constitutive models and the thermodynamic evolution laws for microdamage mechanisms and material viscoelasticity. With the developed fatigue predictor, the effect of the microdamage mechanism on fatigue is elucidated, i.e., the internal damage of the sacrificial network can improve the fatigue life of DN hydrogels. The fatigue life predictor is also adopted to evaluate the effects of some other factors on the fatigue crack nucleation, such as the loading rate, pre-stretching treatment, and water diffusion, identifying feasible loading profiles that could improve material durability. Overall, the theoretical framework and the modeling results in this work are expected to shed light on unveiling the fatigue mechanisms of DN hydrogels and advance the design of hydrogel-based devices.

The axial compressive behaviours of coal gangue concrete-filled steel tube (GCFST) columns after chloride salt corrosion were investigated numerically. Numerical modelling was conducted through the static analysis method by finite element (FE) analysis. The failure mechanism, residual strength, and axial load–displacement curves were validated against tests of the coal gangue aggregate concrete-filled steel tube (GCFST) columns at room and natural aggregate concrete-filled steel tube (NCFST) columns after salt corrosion circumstance. According to the analysis on the stress distribution of the steel tube, the stress value of the steel tube decreased as the corrosion rate increased at the same characteristic point. A parametric analysis was carried out to determine the effect of crucial variation on residual strength. It indicated that material strength, the steel ratio, and the corrosion rate made a profound impact on the residual strength from the FE. The residual strength of the columns exposed to chloride salt was in negative correlation with the corrosion rate. The impact on the residual strength of the column was little, obvious by the replacement rate of the coal gangue. A simplified design formula for predicting the ultimate strength of GCFST columns after chloride salt corrosion exposure was proposed.

Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.

The poor early shrinkage and cracking performances of manufactured sand concrete, waste powder concrete, and recycled aggregate concrete are the main difficulties in engineering applications. To solve these problems, early shrinkage and cracking, strength, and impermeability tests were performed on high-volume stone powder manufactured sand concrete mixed with fly ash and slag powder (FS), a shrinkage-reducing agent (SRA), polyvinyl alcohol (PVA) fibers, and a superabsorbent polymer (SAP). Furthermore, the microstructures and pore structures of these concretes were revealed using nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM). The results showed that the mixture of FS, SRA, PVA fibers, and SAP could effectively inhibit the shrinkage strain and cracking area of the concrete. The effect of the SAP on reducing the early shrinkage of the concrete is the greatest, and the shrinkage strain can be reduced by 76.49%. The PVA fibers had the most obvious effect on inhibiting the early cracking of the concrete, and the total cracking area was reduced by 66.91%. Significantly, the incorporation of the FS can improve the particle gradation and the pore structure and improve its compactness. The PVA fibers not only provide good carriers for cement-based materials but also enhance the bonding force between the particles inside the concrete, filling the pores inside the concrete, inhibiting the loss of water, and reducing the generation of internal microcracks. The FS and PVA can reduce the shrinkage and cracking risk and improve the strength and impermeability of the concrete. Although the SRA and SAP can reduce the shrinkage and cracking risks, it will lead to a significant decrease in the later strength and impermeability. The main reason is that the SRA leads to an increase in micropores in the matrix and microcracks near the aggregate, which are not conducive to the development of the strength and penetration resistance of the MS. Similarly, the SAP can promote the rapid formation of ettringite (Aft) at an early age and improve the early shrinkage, early cracking, and early strength of the concrete. However, with an increase in age, the residual pores, after SAP dehydration, will cause the deterioration of the concrete pore structure, resulting in the deterioration of the strength and impermeability.

The number of excavated tunnels is increasing day by day, and the corresponding engineering scale is also getting increasing. Safe, efficient, and economically beneficial tunnel construction methods are indispensable in the process of crossing mountains and steep ridges in the southwest region. However, behind the improvement of transportation infrastructure in Southwest China is the support provided by the rapid development of blasting industry engineering technology in China. In the process of tunnel construction using the drilling and blasting method, in addition to blasting vibration disasters the phenomenon of overbreak and underbreak caused by blasting construction is a prominent problem. This phenomenon not only affects the safety and stability of the tunnel excavation but also seriously increases the construction cost. Based on a short mountain hard rock tunnel project in southwest China, this paper studies the effect of blasting construction on the blasting vibration of adjacent structures and the influence of tunnel contour forming quality. Through the monitoring and analysis of in situ blasting vibration, the Sadowski formula is used to study the attenuation law of blasting vibration velocity in different tunnel sites, which provides a theoretical basis for tunnel blasting vibration control. This article compares the use of overbreak and underbreak value with the traditional method to determine the degree of overbreak and underbreak. It introduces the analysis of contour section fractal dimension value and uses fractal theory in the Python image processing module to accurately and quantitatively describe the problems of tunnel overbreak and underbreak. The feasibility and accuracy of this method have been verified, by combining the total station and 3D laser scanner results of overbreak and underbreak measurements of the Brenner Base Tunnel and a short hard rock tunnel in a mountainous area of southwestern China. The blasting scheme was optimized from the aspects of cut hole form, detonator interval time, and peripheral hole charge structure, and the rationality of the optimized scheme was verified according to the on-site blasting experiments. It has a profound influence on strengthening the protection of adjacent tunnel structures and improving the economic benefit of mountain highway projects.

Food poisoning caused by Staphylococcal enterotoxins (SEs) is prevalent globally, making efficient detection of these toxins very important. Traditionally, liquid chromatography–mass spectrometry required immunosorbent enrichment by magnetic bead-coupled antibodies obtained by animal-specific immunization. However, this method is time-consuming and costly. In this study, two recombinant protein capture molecules were designed based on the principle of toxins binding to Major Histocompatibility Complex (MHCII) and T cell receptor (TCR) molecules. The two capture molecules are called MHCII and MHCII-D10. The design of the MHCII and TCR-D10 was achieved through searching for the binding site protein sequence of Staphylococcal enterotoxins in the relevant literature, and MHCII-D10 was to link MHCII sequence with TCR-D10 sequence using linker (G4S)3 linking peptide. These capture molecules were shown to effectively bind to seven types of toxins and to capture SEs in various matrices. The digestion time, ratio, and temperature were further optimized, reducing the overall digestion time to just 2 h. The specificity, linearity, sensitivity, precision (RSD%), and recovery of the two methods were verified by liquid chromatography–mass spectrometry. When the MHCII and MHCII-D10 captured the toxins, the limit of quantification (LOD) in the 1 × PBS, plasma, and milk matrices ranged from 1.5625 to 100 fmol/µL, with the recovery rate ranging from 18.4% to 96%. The design of these capture molecules eliminates the need for animal-specific immunization, simplifying the pre-detection process and avoiding ethical concerns. This development holds significant promise for clinical diagnosis and reference.

The paper presents an analysis of the innovative connector for manufacturing a steel–concrete composite beam. The connector consists of a corrugated metal sheet in the shape of a dovetail and shot nails. The nails are shot through the sheet fold into the flange of the steel I-section. Experimental studies of push-out tests were carried out. The conducted tests proved that the proposed solution can be applied as the fastener for steel–concrete composite beams for the construction of ceilings in utility public buildings with small beam’s span. Considering the criteria presented in the Eurocode 4 standard and the results of the experiments, it was proven that all analyzed types of fasteners are ductile. The connector made of sheet with a thickness of 1.00 mm and 2 nails is characterized by a breaking load of 30.83 kN. The load-bearing capacity of the fastener can be adjusted by changing the corrugated sheet thickness and changing the number of nails shot in the single fold of the sheet.

Small-scale low-altitude unmanned aerial vehicles (UAVs) equipped with perception capability for military targets will become increasingly essential for strategic reconnaissance and stationary patrols in the future. To respond to challenges such as complex terrain and weather variations, as well as the deception and camouflage of military targets, this paper proposes a hybrid detection model that combines Convolutional Neural Network (CNN) and Transformer architecture in a decoupled manner. The proposed detector consists of the C-branch and the T-branch. In the C-branch, Multi-gradient Path Network (MgpNet) is introduced, inspired by the multi-gradient flow strategy, excelling in capturing the local feature information of an image. In the T-branch, RPFormer, a Region–Pixel two-stage attention mechanism, is proposed to aggregate the global feature information of the whole image. A feature fusion strategy is proposed to merge the feature layers of the two branches, further improving the detection accuracy. Furthermore, to better simulate real UAVs’ reconnaissance environments, we construct a dataset of military targets in complex environments captured from an oblique perspective to evaluate the proposed detector. In ablation experiments, different fusion methods are validated, and the results demonstrate the effectiveness of the proposed fusion strategy. In comparative experiments, the proposed detector outperforms most advanced general detectors.

This study aimed to investigate whether a dietary 25-OHD3 addition improved the performance, egg quality, blood indexes, antioxidant status, jejunal morphology, and tibia quality of aged laying hens compared to a dietary VD3 addition. A total of 270 Hy-Line Brown laying hens at 55 wk of age were randomly assigned to three dietary treatments with six replicates (15 birds per replicate with 3 birds per cage). Chickens were fed a corn–soybean meal diet supplementation of 4000 IU/kg VD3 (control group), 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 (experimental group 1), or 50 μg/kg 25-OHD3 and 4000 IU/kg VD3 (experimental group 2) for 12 weeks. The results demonstrated that 25-OHD3 caused a significant increase in the laying rate, especially in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group; the laying rate reached the maximum compared with other groups after 12 weeks (p < 0.05). However, there were no significant effects on the average egg weight, average daily feed intake, or feed-to-egg ratio (p > 0.05). A dietary supplementation of 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 provided an improved eggshell strength, thick albumen height, and Haugh unit after 12 weeks (p < 0.05). Further analysis of the blood indexes showed that alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, calcium, and phosphorus were enhanced significantly in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group, while the content of total bilirubin decreased significantly (p < 0.05). In addition, the 25-OHD3 addition in diets improved the calcium and phosphorus contents in the serum (p < 0.05). The concentrations of 25-OHD3, parathyroid hormones, follicle-stimulating hormone, and progesterone were increased in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group, and the levels of cortisol, calcitonin, bone gla protein, and endotoxin in the serum reached a minimum in the 50 μg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05), which constitutes an advantage for the aged laying hens. The antioxidant enzyme activities and free radical scavenging abilities in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group increased markedly, and the MDA level decreased significantly in the 50 μg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05). Improvements in jejunal morphology and intestinal integrity resulted in an increased villi-length-to-crypt-depth ratio in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group (p < 0.05). Dietary 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 additions improved the tibia quality, including fresh tibia weight, strength, mineral content (Ca), and trabeculae area (p < 0.05). Taken together, compared with the dietary VD3 addition, dietary supplementation of 25-OHD3 supported a stable physiological status for sustained egg production, egg quality, and bone quality in late-phase laying hens, and the addition levels of 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 had the best effect. Therefore, this could provide a theoretical basis for the use of 25-OHD3 as a substitute forVD3.

The dual-drive ball screw pair serves as a crucial element within the fixed gantry machine tool with cross-rail movement. When in service, the dual-drive ball screw pair experiences variations in axial load, impacting the contact load distribution of the ball screw pair. A calculation model for determining the axial load offset of the dual-drive ball screw pair is proposed to investigate the variation in axial load. The impact of the geometric error associated with the guide rail and the position of the slide are considered. This paper presents the contact load distribution model for the dual-drive ball screw pair. This study investigates the contact load and contact angle distribution of the dual-drive ball screw pair during the machine tool in service. Additionally, based on fractal theory, the stiffness models of individual micro-convex body and contact surfaces have been established. This study provides a comprehensive analysis of the contact stiffness of the ball screw pair, considering the influence of guide rail geometric error and slide position. In addition, the three-dimensional surface morphology of ball screw pair is obtained by experiments. This paper investigates the contact stiffness distribution of dual-drive ball screw pair during service.

Light field imaging involves reconstructing a 4D light field from a 3D focal stack, which makes it challenging to reconstruct the light field from incomplete projection data. To address this problem, a linear projection system is established to model the focal stack imaging process using discrete refocusing equations. Based on this system, we propose the block Landweber iterative method to find the least-squares solution. This method computes the sparse matrix while iterating, which overcomes the problem of data storage. The 2-norm of the block matrix is utilized as the weighted matrix to normalize every block matrix on an identical scale, delivering an effective relaxation strategy under the convergence condition in the inconsistent case, which yields better reconstruction results and accelerates the convergence speed. The experimental results based on the image quality assessments of reference and non-reference images show that our method achieved better reconstruction results compared to other relevant common methods, even with fewer focal stacks and higher angle resolution.

In this paper, a finite element model of concrete-filled steel tubular (CFST) columns under compression and lateral impact is developed and validated against previous experiments. After analyzing the influence of axial compression on the impact performance of CFST columns, the effects of eccentricity, material strength, and steel ratio on the dynamic compression-bending performances of CFST columns subjected to lateral impact are discussed. The simulated results show that at different axial compression ratios, CFST columns show overall bending failure under lateral impact. The axial force ratio below 0.2 shows a positive effect on the impact resistance of CFST columns, otherwise the axial force would degrade the impact resistance of CFST columns. Eccentricity has a negative effect on the dynamic compression-bending performance of CFST columns. The increase in the concrete strength has little effect on the dynamic compression-bending performance of the CFST columns under lateral impact and eccentric compression. The increases in steel strength and steel ratio can improve the dynamic compression-bending performances of the CFST columns under lateral impact and eccentric compression. Even though the prediction formula for the dynamic compression-bending performance of CFST columns shows good fitness with the simulated results, it is modified to have sufficient strength reserves for design applications.

Very rich scholarly works have been produced to perform a comparative study between Emerson and Zhuang Zi. Many scholars in their comparative research have tried to find how Emerson and the transcendentalists such as Thoreau borrow ideas from Daoism. In this article, I will take a different approach. I aim to find how Emerson and Zhuang Zi’s pursuit of spirituality in nature shapes different types of sense of place. The concept of spirituality is related to the pursuit of meaning in life and self-transcendence. This concept has gradually gained attention from the branches of religion, philosophy, geography, and psychology since, currently, due to the fast urbanization process, more people are separated from their land and move into cities. I will make a comparison between Emerson and Zhuang Zi from the concepts of spirituality, nature, and place. This perspective will shed light on the question of the conservation of various places due to their value and meaning, although I will not discuss conservation issues in this paper. In this article, I will first give a brief introduction to the meaning of spirituality by focusing on the three dimensions of this concept, which include meaning, self-transcendence, and spiritual practices. Then, I will discuss how the concept of nature in Emerson and Zhuang Zi’s works is related to these three dimensions. Finally, I will examine why Emerson and Zhuang Zi treat wilderness and agricultural land, respectively, as a place.

Differential Code Bias (DCB) is a crucially systematic error in satellite positioning and ionospheric modeling. This study aims to estimate the BeiDou-3 global navigation satellite system (BDS-3) satellite DCBs by using the single-frequency (SF) uncombined Precise Point Positioning (PPP) model. The experiment utilized BDS-3 B1 observations collected from 25 International GNSS Service (IGS) stations located at various latitudes during March 2023. The results reveal that the accuracy of estimating B1I-B3I DCBs derived from single receiver exhibits latitude dependence. Stations in low-latitude regions show considerable variability in the root mean square (RMS) of absolute offsets for satellite DCBs estimation, covering a wide range of values. In contrast, mid- to high-latitude stations demonstrate a more consistent pattern with relatively stable RMS values. Moreover, it has been observed that the stations situated in the Northern Hemisphere display a higher level of consistency in the RMS values when compared to those in the Southern Hemisphere. When incorporating estimates from all 25 stations, the RMS of the absolute offsets in satellite DCBs estimation consistently remained below 0.8 ns. Notably, after excluding 8 low-latitude stations and utilizing data from the remaining 17 stations, the RMS of absolute offsets in satellite DCBs estimation decreased to below 0.63 ns. These enhancements underscore the importance of incorporating a sufficient number of mid- and high-latitude stations to mitigate the effects of ionospheric variability when utilizing SF observations for satellite DCBs estimation.

Little work has been carried out to predict the comfort of aircraft seats, a component in close contact with the human body during travel. In order to more accurately predict the nonlinear and complex relationship between subjective and objective evaluations of comfort, this paper proposes a prediction method based on the Improved Particle Swarm Algorithm (IPSO) and optimized Support Vector Machine Regression (SVR). Focusing on the problems of the too-fast convergence and low accuracy of the traditional particle swarm algorithm (PSO), the improved particle swarm algorithm (IPSO) is obtained by linearly decreasing the dynamic adjustments of inertia weight ω, self-learning factor c1, and social factor c2; then, the penalty parameter C and kernel function parameter σ of SVR are optimized by the IPSO algorithm, and the comfort prediction of IPSO-SVR is established. The prediction accuracy of IPSO-SVR was 94.00%, the root mean square error RMSE was 0.37, the mean absolute value error MAE was 0.32, and the goodness of fit R2 was 0.92. The results show that the optimized IPSO-SVR prediction model can more accurately predict seat comfort under different angles and backrest tilt angles and can provide reference and research value for related industries. The results show that the optimized nonlinear prediction model of IPSO-SVR has higher accuracy, and its prediction method is feasible and generalizable, meaning it can provide a reliable basis for the prediction of seat comfort under different angles and backrest inclinations, as well as providing reference and research value for related industries.

In offshore structures such as offshore wind turbine jacket foundations, prolonged exposure to wind and wave loads can lead to fatigue failure, especially at the joint connections. Currently, international codes primarily evaluate the fatigue performance of tubular joints using the hot spot stress (HSS) method, with stress concentration factor (SCF) being the most crucial parameter. Numerous studies have investigated the SCF of tubular joints and proposed corresponding calculation formulas. However, most of these studies have focused on simple basic loading cases. To comprehensively understand the distribution pattern of the HSS method at spatial tubular joints, this study selects the spatial CHS KK-joints as the research subject and performs the HSS testing on spatial KK-joints. The research indicates that, in CHS joints, the distribution of the HSS on the chord side remains consistent under tensile or compressive loading conditions along the brace axis. Additionally, within spatial joints, the loading conditions of neighboring braces near the reference brace significantly affect the distribution of HSS on the chord side and exhibit varying spatial effects on the SCF. Furthermore, this study applies recommended calculation formulas from codes to analyze the experimental results. The findings reveal significant discrepancies between the SCF calculation formulas recommended by CIDECT and the test results, rendering it inadequate for accurately calculating the SCF of spatial KK-joints. Therefore, further research is required to develop suitable calculation formulas for SCFs in spatial KK-joints.

Concrete with light weight and pervious performance has been widely recognized as an effective and sustainable solution for reducing the negative impacts of urbanization on the environment, as it plays a positive role in urban road drainage, alleviating the urban heat island effect and thermal insulation, as well as seismic performance, etc. This research paper presents a feasibility study of pervious concrete preparation with ceramsite as aggregate. First, pervious concrete specimens with different types of aggregates at various water–cement ratios were prepared, and the mechanical properties of pervious concrete specimens were evaluated based on the compressive strength test. Then, the permeability properties of the pervious concrete specimens with different types of aggregates at various water–cement ratios were characterized. Meanwhile, statistical analysis and regression fitting were conducted. Finally, the analysis of the freeze–thaw durability of pervious concrete specimens with ceramsite as aggregate according to indexes including quality loss rate and strength loss rate was performed. The results show that as the water–cement ratio increased, the compressive strength and permeability coefficient of pervious concrete generally decreased. Compressive strength and permeability coefficient showed a great correlation with the water–cement ratio; the R2 values of the models were around 0.94 and 0.9, showing good regression. Compressive strength was mainly provided by the strength of the aggregates, with high-strength clay ceramsite having the highest 28-day compressive strength value, followed by ordinary crushed-stone aggregates and lightweight ceramsite. Porosity was mainly influenced by the particle size and shape of the aggregates. Lightweight ceramsite had the highest permeability coefficient among different types of cement-bound aggregates, followed by high-strength clay ceramsite and ordinary crushed-stone aggregates. The quality and compressive strength of pervious concrete specimens decreased with the increase in freeze–thaw cycles; the quality loss was 1.52%, and the compressive strength loss rate was 6.84% after 25 freeze–thaw cycles. Quadratic polynomial regression analysis was used to quantify the relationship of durability and freeze–thaw cycles, with R2 of around 0.98. The results provide valuable insights into the potential applications and benefits of using ceramsite as an aggregate material in pervious concrete for more sustainable and durable infrastructure projects.

Epsilon toxin (ETX) is an exotoxin produced by type B and D Clostridium perfringens that causes enterotoxemia or necrotic enteritis in animals such as goats, sheep, and cattle. Vaccination is a key method in preventing such diseases. In this study, we developed a new type of dissolving microneedle patch (dMN) with a nanoparticle adjuvant for enhanced immune response to deliver the rETXY196E-C protein vaccine. We chose FDA-approved poly(lactic-co-glycolic acid) (PLGA) to prepare nanospheres as the vaccine adjuvant and introduced dimethyldioctadecylammonium bromide (DDAB) to make the surface of PLGA nanoparticles (PLGA NPs) positively charged for antigen adsorption. PLGA NPs with a diameter of 100~200 nm, a surface ZETA potential of approximately +40 mV, and good safety were successfully prepared and could effectively adsorb rETXY196E-C protein. Using non-toxic and antibacterial fish gelatin as the microneedle (MN) matrix, we prepared a PLGA-DDAB dMN vaccine with good mechanical properties that successfully penetrated the skin. After immunization of subcutaneous (SC) and dMN, antibody titers of the PLGA and Al adjuvant groups were similar in both two immune ways. However, in vivo neutralization experiments showed that the dMN vaccines had a better protective effect. When challenged with 100 × LD50 GST-ETX, the survival rate of the MN group was 100%, while that of the SC Al group was 80%. However, a 100% protective effect was achieved in both immunization methods using PLGA NPs. In vitro neutralization experiments showed that the serum antibodies from the dMN and SC PLGA NPs groups both protect naive mice from 10 × LD50 GST-ETX attack after being diluted 20 times and could also protect MDCK cells from 20 × CT50 GST-ETX attack. In conclusion, the PLGA-DDAB dMN vaccine we prepared has good mechanical properties, immunogenicity, and protection, and can effectively prevent ETX poisoning. This provides a better way of delivering protein vaccines.

Convolutional neural networks (CNNs) have received increased attention in endoscopic images due to their outstanding advantages. Clinically, some gastric polyps are related to gastric cancer, and accurate identification and timely removal are critical. CNN-based semantic segmentation can delineate each polyp region precisely, which is beneficial to endoscopists in the diagnosis and treatment of gastric polyps. At present, just a few studies have used CNN to automatically diagnose gastric polyps, and studies on their semantic segmentation are lacking. Therefore, we contribute pioneering research on gastric polyp segmentation in endoscopic images based on CNN. Seven classical semantic segmentation models, including U-Net, UNet++, DeepLabv3, DeepLabv3+, Pyramid Attention Network (PAN), LinkNet, and Muti-scale Attention Net (MA-Net), with the encoders of ResNet50, MobineNetV2, or EfficientNet-B1, are constructed and compared based on the collected dataset. The integrated evaluation approach to ascertaining the optimal CNN model combining both subjective considerations and objective information is proposed since the selection from several CNN models is difficult in a complex problem with conflicting multiple criteria. UNet++ with the MobineNet v2 encoder obtains the best scores in the proposed integrated evaluation method and is selected to build the automated polyp-segmentation system. This study discovered that the semantic segmentation model has a high clinical value in the diagnosis of gastric polyps, and the integrated evaluation approach can provide an impartial and objective tool for the selection of numerous models. Our study can further advance the development of endoscopic gastrointestinal disease identification techniques, and the proposed evaluation technique has implications for mathematical model-based selection methods for clinical technologies.

In order to study the variation of mechanical properties of steel under acid rain corrosion conditions in northern China, monotonic tensile tests were conducted on Q235 steel with a thickness of 3.0 mm and 4.5 mm using a method of artificially prepared simulated acid rain solution for indoor accelerated corrosion. The results show that the failure mode of corroded steel standard tensile coupon includes normal fault and oblique fault. The failure patterns of the test specimen show that the thickness of the steel and corrosion rate affected the corrosion resistance. Larger thicknesses and lower corrosion rates will delay the failure mode of corrosion on steel. The strength reduction factor (Ru), deformability reduction factor (Rd) and energy absorption reduction factor (Re) decrease linearly with the increasing corrosion rate from 0% to 30%. The results are interpreted also from the microstructural point of view. The number, size, and distribution of the pits are random when the steel is subjected to sulfate corrosion. The higher the corrosion rate, the clearer, denser, and more hemispherical the corrosion pits. The microstructure of steel tensile fracture can be divided into intergranular fracture and cleavage fracture. As the corrosion rate increases, the dimples at the tensile fracture gradually disappear and the cleavage surface gradually increases. An equivalent thickness reduction model is proposed based on Faraday’s law and the meso-damage theory.

In order to better simulate the actual working conditions of wind turbines more realistically, this paper adopts the two-way fluid–structure coupling method to study the NREL 5 MW wind turbine, considering the blade coupling deformation and equivalent stress and strain distribution of the blades with different internal structures under different working conditions. The results show that the maximum equivalent stress and strain distribution of the beam–structure wind turbine blade was near the leading edge of the blade. The maximum equivalent stress and strain distribution of the shell structure wind turbine blade was near the leading edge of the blade root, and the dangerous area is obvious but smaller than that of the beam-type wind turbine. The coupled deformation of a wind turbine model with a shell structure blade with a web is significantly reduced, and the equivalent stress and strain distribution of the skin is similar to that of the shell structure, but the numerical value and the maximum equivalent stress distribution area are significantly smaller. From the comparison of the three, the shell structure blade with a web is the best.

On the basis of elaborating on the regional geological background, this paper analyzes the lithological and sedimentary characteristics and explorative prospects of new strata with oil and gas in the southern and surrounding areas of Dayangshu Basin. Based on the latest high-precision airborne gravity and magnetic comprehensive survey data, combined with the latest data from geological explorations, physical surveys, and drilling, and the use of basin structure layering combination methods, we clarified the characteristics of the bottom of the Jurassic–Cretaceous and the occurrence characteristics of the Upper Paleozoic in the study area and revealed the determinative effect of multi-period structures on the most important sedimentary layers. Then, we summarized the accumulation conditions and prediction methods of hydrocarbons and proposed the oil and gas prospects of these deep new strata. The results show that the Liuhe Sag in Dayangshu Basin, the depression in the northeast of Longjiang Basin, and the northern parts of the Taikang swell have good source–reservoir–cap combination conditions and favorable structural characteristics for oil and gas, where there is a high potential for exploration.

This paper addresses a detailed analysis of the ice–structure interaction process of the phase-locked ice crushing (PLC) against offshore structures. Directly measured ice load, structure response data, and in situ observation from the field measurements on the Molikpaq lighthouse and jacket platform were used in the study. This paper summarizes a new ductile damage-collapse (DDC) failure mechanism for the PLC process. The DDC mechanism shows that the ice failure is a discrete ductile crushing process rather than a ductile–brittle transition process. The analysis identifies that the ice has a failure length in PLC and this failure length plays an important role in understanding the interaction. It reveals that PLC can occur on most vertical-sided offshore structures when the velocity of the ice sheet falls within the range of the failure length divided by the natural period of the structure. This paper proposes that this relationship between ice failure length and the natural period of the structure can be used as one of the PLC occurrence conditions. The DDC failure mechanism provides a basis for another technical route to solve the PLC problem.

Soil erosion and water loss are serious problems on the rocky desertification slopes in the karst dynamic system of southwest China. The lack of soil and shortage of water restrict the ecological restoration of the regional slopes and utility of water resources. Therefore, a new slab trench capable of storing soil and water in layers on rocky desertification slopes is introduced in this paper to promote vegetation restoration. To explore the water-storing and -holding capacity of the new type of vegetated slab trench, five groups of model experiments were carried out on the vegetated slab trench under different rainfall intensities and different numbers of plants. Under rainfall and then following dry conditions, the effects of rainfall intensity and the number of plants on the water-storing and -holding capacity of vegetated slab trench models were compared and analyzed. Water-storing and -holding capacity was further explored in three groups of models with single planting or combinations of plants including water stored only in succulent root plant, only in succulent stem plant, or in mixed plants. The test results show that the new type of vegetated slab trench can effectively help to store and hold water. In the rainfall period, due to the runoff of the rainfall not being considered, the greater the rainfall intensity, the higher the water storage efficiency; the more vegetation implanted, the greater the blocking effect of the plant canopy during falling rainwater, and the more reduction is induced on the water storage efficiency of the vegetated slab trench. In the following dry period, both the succulent root plant and succulent stem plant have strong water storage capacity, but the succulent root plant has a stronger capacity for water storage. The growth status of the mixed plants was better than that of single planting, which may be due to the water complementarities between the succulent root plant and succulent stem plant in a mixed planting manner. This study is important for solving the problem of soil erosion and water loss in rocky desertification slopes, and it helps to restore the ecological environment of the area.

Epsilon toxin (ETX), produced by type B and D strains of Clostridium perfringens, can cause fatal enterotoxaemia in ruminant animals, particularly sheep, cattle, and goats. Previous studies show that the cytotoxicity of ETX is dependent on the integrity of lipid rafts, the maintenance of which is ensured by cholesterol. Zaragozic acid (ZA) is a statin drug that reduces the synthesis of squalene, which is responsible for cholesterol synthesis. In this study, ZA significantly reduced the toxicity of ETX in Madin–Darby canine kidney (MDCK) cells. We show that ZA does not affect the binding of ETX to MDCK cells, but propidium iodide staining (PI) and Western blotting confirmed that ZA significantly disrupts the ability of ETX to form pores or oligomers in MDCK cells. Additionally, ZA decreased the phosphatidylserine exposure on the plasma membrane and increased the Ca2+ influx of the cells. Results of density gradient centrifugation suggest that ZA decreased the number of lipid rafts in MDCK membranes, which probably contributed to the attenuation of pore-formation. Moreover, ZA protected mice against ETX in vivo. All mice pre-treated with ZA for 48 h before exposure to an absolute lethal dose of ETX (6400 ng/kg) survived. In summary, these findings provide an innovative method to prevent ETX intoxication. Considering many pore-forming toxins require lipid rafts, we tested and found ZA also inhibited the toxicity of other toxins such as Clostridium perfringens Net B and β-toxin (CPB) and Staphylococcus aureus α-hemolysin (Hla). We expect ZA can thus be developed as a broad-spectrum medicine for the treatment of multiple toxins. In addition, other statins, such as lovastatin (LO), also reduced the toxicity of ETX. These findings indicate that statin medicines are potential candidates for preventing and treating multiple toxin-induced diseases.

Aiming to provide a solution for natural resource consumption and agricultural waste pollution, jujube nucleus is utilized as a substitute for coarse aggregate in the preparation of lightweight aggregate concrete. The effect of the jujube nucleus (JN) replacement ratio and the elevated temperature on the uniaxial compressive stress–strain curves of jujube nucleus concrete (JNC) are experimentally studied. The results show that the failure of the JNC prisms became more serious with the increase in the JN replacement ratio. The linear proportion in ascending branch and the descending slope of the stress–strain curves for JNC increased gradually with the increase in the JN replacement ratio and elevated temperature, which is probably owing to the higher porosity and lower stiffness of the jujube nucleus, compared to natural aggregate. Moreover, as the JN replacement ratio and the elevated temperature increase, the peak stress and elastic modulus in the stress–strain curves of JNC decrease gradually, whilst an increase in the peak strain shows up, which is possibly due to the growth of hydrate calcium silicate and calcium hydroxide hampered by sucrose molecules. Based on the test results, a series of theoretical formulas are proposed to predict the compressive performance of JNC. A material constitutive model is developed for describing the stress–strain relationship of JNC by considering the JN replacement ratio and elevated temperature.

With the exploration and development of high-temperature and high-salt deep oil and gas, more rigorous requirements are warranted for the performance of water-based drilling fluids (WBDFs). In this study, acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, diallyl dimethyl ammonium chloride, and N-vinylpyrrolidone were synthesized by free radical copolymerization in an aqueous solution to form a temperature and salt-resistant zwitterionic polymer gel filtration loss reducer (AADN). The zwitterionic polymer had excellent adsorption and hydration groups, which could effectively combine with bentonite through hydrogen bonds and electrostatic attraction, strengthening the hydration film thickness on the surface of bentonite, and promoting the stable dispersion of drilling fluid. In addition, the reverse polyelectrolyte effect of zwitterionic polymers strengthened the drilling fluid’s ability to resist high-temperature and high-salt. The AADN-based drilling fluid showed excellent rheological and filtration control properties (FLAPI < 8 mL, FLHTHP < 29.6 mL) even after aging at high-temperature (200 °C) and high-salt (20 wt% NaCl) conditions. This study provides a new strategy for simultaneously improving the high-temperature and high-salt tolerance of WBDFs, presenting the potential for application in drilling in high-temperature and high-salt deep formations.

Background: As a Class A bioterrorism agent, botulinum neurotoxin serotype A (BoNT/A) carries the risk of being used by terrorists to cause mass poisoning. The microneedle (MN) patch has a great potential for application as a novel vaccine delivery method. The aim of this study is to develop a thermally stable, dissolving microneedle patch for the delivery of a recombinant protein vaccine using a recombinant C-terminal heavy chain of BoNT/A (Hc of BoNT/A, AHc) to prevent botulism. Methods: Fish gelatin, a natural non-toxic and bacteriostatic material, was selected as the microneedle matrix for the preparation of the dissolving microneedle vaccine. Subsequently, the mechanical performance, bacteriostatic properties, vaccination effect, and stability of the microneedle patches were evaluated using instruments such as the displacement-force test station and optical coherence tomography (OCT) scanner. Results: Fish gelatin matrix at high concentrations has good bacteriostatic properties, and excellent mechanical performance and vaccination effect, meeting the necessities of a vaccine. In both in vivo and in vitro neutralization experiments, MN vaccines containing different antigen doses achieved the same protective efficacy as subcutaneous vaccinations, protecting mice against 106 LD50 of BoNT/A injected intraperitoneally. Thermal stability analysis of the MN vaccines revealed that the fish gelatin matrix protected the AHc vaccine from protein denaturation even after 7 days of storage at 37 °C and enabled the vaccine patches to maintain good immunogenicity and protective efficacy even after 6 months of storage at room temperature. Conclusion: In this study, we successfully prepared a bacteriostatic MN patch using a fish gelatin matrix that not only has a good vaccination effect, but also obviates the need for a cold chain for the AHc vaccine, providing the possibility of rapid, painless, and large-scale vaccination.

B and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule that mediates the escape of tumor cells from immunosurveillance. Consequently, BTLA and its ligand herpesvirus entry mediator (HVEM) are potentially immunotherapeutic targets. However, the potential effects of BTLA on tumor cells remain incompletely unknown. Here, we show that BTLA is expressed across a broad range of tumor cells. The depletion of BTLA or HVEM promotes cell proliferation and colony formation, which is reversed by the overexpression of BTLA in BTLA knockout cells. In contrast, overexpression of BTLA or HVEM inhibits tumor cell proliferation and colony formation. Furthermore, the proliferation of a subpopulation with high BTLA was also significantly slower than that of the low BTLA subpopulation. Mechanistically, the coordination of BTLA and HVEM inhibits its major downstream extracellular regulated protein kinase (ERK1/2) signaling pathway, thus preventing tumor cell growth. This study demonstrates that tumor cell-intrinsic BTLA/HVEM is a potential tumor suppressor and is likely to have a potential antagonist for immunotherapy, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.

Aortic dissection (AD) is a lethal aortic pathology without effective medical treatments since the underlying pathological mechanisms responsible for AD remain elusive. Matrix metalloproteinase-8 (MMP8) has been previously identified as a key player in atherosclerosis and arterial remodeling. However, the functional role of MMP8 in AD remains largely unknown. Here, we report that an increased level of MMP8 was observed in 3-aminopropionitrile fumarate (BAPN)-induced murine AD. AD incidence and aortic elastin fragmentation were markedly reduced in MMP8-knockout mice. Importantly, pharmacologic inhibition of MMP8 significantly reduced the AD incidence and aortic elastin fragmentation. We observed less inflammatory cell accumulation, a lower level of aortic inflammation, and decreased smooth muscle cell (SMC) apoptosis in MMP8-knockout mice. In line with our previous observation that MMP8 cleaves Ang I to generate Ang II, BAPN-treated MMP8-knockout mice had increased levels of Ang I, but decreased levels of Ang II and lower blood pressure. Additionally, we observed a decreased expression level of vascular cell adhesion molecule-1 (VCAM1) and a reduced level of reactive oxygen species (ROS) in MMP8-knockout aortas. Mechanistically, our data show that the Ang II/VCAM1 signal axis is responsible for MMP8-mediated inflammatory cell invasion and transendothelial migration, while MMP8-mediated SMC inflammation and apoptosis are attributed to Ang II/ROS signaling. Finally, we observed higher levels of aortic and serum MMP8 in patients with AD. We therefore provide new insights into the molecular mechanisms underlying AD and identify MMP8 as a potential therapeutic target for this life-threatening aortic disease.

Over the last three years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related health crisis has claimed over six million lives and caused USD 12 trillion losses to the global economy. SARS-CoV-2 continuously mutates and evolves with a high basic reproduction number (R0), resulting in a variety of clinical manifestations ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS) and even death. To gain a better understanding of coronavirus disease 2019 (COVID-19), it is critical to investigate the components that cause various clinical manifestations. Single-cell sequencing has substantial advantages in terms of identifying differentially expressed genes among individual cells, which can provide a better understanding of the various physiological and pathological processes. This article reviewed the use of single-cell transcriptomics in COVID-19 research, examined the immune response disparities generated by SARS-CoV-2, and offered insights regarding how to improve COVID-19 diagnosis and treatment plans.

Underground void subsidence hazards, especially mine goaf, have now become one of the major social problems affecting the well-being of civilians and development in China. The objective of this study was to propose a kind of strong thixotropic engineering slurry and filling treatment for use in underground void subsidence hazards. The optimal agent ratio for thixotropic cement slurry/mortar was obtained by indoor tests, where the rheological agent is 7.5% compared to the weight of cement, the water–solid ratio is in the range of 0.7~0.8, and the aeolian sand ratio can be 0~1.5 times that of cement. The rheological properties of slurry and mortar were tested using a Brookfield RST-SST rheometer. The results show that aeolian sand can be used as thixotropic cement mortar for a backfilling treatment for underground voids (mine goaf). The static yield stress increases non-linearly compared to existing thixotropic models. The stress decays sharply with shearing (the shear rate is more or less 10 s−1) and then the stress increases with the increase in shear rate (the shear rate is more than 10 s−1). The increase in the stress of the slurry is greater than in the mortar. A natural logarithmic function between yield stress and rest time (only 1 parameter), an exponential function with two parts for stress–shear rate (a rheology model, with only 3 parameters), and an exponential function for the accumulation law (only 2 parameters) were proposed in turn.

The occurrence characteristics of magnetite and the methods to quickly and effectively explore are important topics for ore prospecting in the new era. Taking northeast of Hebei Province of China as an example, this article aimed at an important strategic mineral of magnetite, then discussed its distribution characteristics and aeromagnetic exploration methods of it. First of all, we discuss the occurrence characteristics of sedimentary metamorphic and magmatic magnetite. Then, using the latest high-precision aeromagnetic data, combined with the geological outcrops, known iron deposits, ground magnetic surveys, and verification, we studied the relationship between the aeromagnetic anomalies and iron deposits through potential field conversion processing of the reduction to the pole, vertical derivative, upward continuation and residual anomaly, and the forward modeling and inversion methods of 2.5 D optimization fitting. Next, we summarize the metallogenic conditions and attributes of aeromagnetic prospecting and make magnetite predictions. In addition, it has suitable magnetite prospecting potential in the Laochenjia, Dabai, Jiuwuying, Beierying, Sidaogoumen, and Wuyingzi aeromagnetic anomaly regions. In conclusion, these regions have aeromagnetic anomalies with high amplitudes, large scales, and favorable metallogenic backgrounds for magmatic rocks, strata, and structures caused by concealed magnetite. In addition, they have great prospecting potential. Eventually, we hope this research method in this article can provide a reference for magnetite exploration in other areas with similar geological conditions.

Soil salinization is a problem that arouses the world’s attention. Soil salinity is an important limitation for agriculture production in coastal area. Phosphorus is a very important nutrient element in the process of plant growth, and its effectiveness affects plant growth to a great extent. In this study, soil available phosphorus and its component in Hedley phosphorus classification were found to be affected by soil salinity in coastal areas of Jiangsu Province. Several key environmental factors changed under the saline environment of the coastal areas, such as soil salinity, soil pH, and soil alkaline phosphatase activity. These environmental factors were significantly correlated with soil available phosphorus. Results showed that there were significant correlations between soil salinity and other environmental factors, and soil salinity and alkaline phosphatase activity were the main influencing factors of soil available phosphorus in this study. Significant positive correlation was found between alkaline phosphatase activity and soil salt content, and soil salinity was considered as the most important impact factor for soil available phosphorus as it affected the surrounding environment, and the soil alkaline phosphatase could be considered as the direct influencing factor for soil available phosphorus. Analysis between the soil alkaline phosphatase activity and phosphorus component showed that soil alkaline phosphatase activity could increase the proportion of active inorganic phosphorus and medium active inorganic phosphorus in soil phosphorus pool, which explained the effect of soil alkaline phosphatase activity on soil available phosphorus.

In the interaction between waves and structures, the maximum wave run-up height on the surface of the structure and the wave field distribution around the cylinder are important factors to be considered in the design of marine structures. In this paper, the open source software OpenFOAM is used to simulate the wave run-up phenomenon of a truncated cylinder under regular waves by solving the Reynolds-averaged Navier–Stokes equation. The established numerical model is verified with the experimental data, and the good consistency demonstrates the accuracy in simulating the interaction between waves and fixed truncated cylinders. The numerical results show that the draft of the cylinder under regular waves has little effect on its maximum wave run-up height, but has a significant effect on the horizontal wave force. At the same wave steepness, the radial dimensionless run-up height increases with the increase of scattering parameters ka, where k is the wave number and a is the cylinder radius. The radial run-up height decreases gradually along the radial direction in the upstream, and increases gradually along the radial direction in the downstream.

The aim of this study was to investigate the properties of fiber-reinforced pervious concrete. Ordinary cement, silica fume, coarse aggregate, and basalt fibers were used to produce the concrete mix. The fibers were mixed with pervious concrete at the levels of 0 kg/m3, 2 kg/m3, 4 kg/m3, 6 kg/m3, and 8 kg/m3 to the investigate their influence on the mechanical and physical properties of pervious concrete. It could be observed that the cubic compressive strength, axial compressive strength, and flexural strength increased and then decreased as the content of basalt fiber increased, while the permeability and porosity of the pervious concrete decreased with the increase in the basalt fiber content. The mesostructure of pervious concrete was also studied through industrial computed tomography (ICT); the testing phenomenon showed that the fibers had a significant influence on the arrangement of the aggregate, cement paste, and the interfacial transition zone, and excessive basalt fiber resulted in poor characteristics of the interfacial transition zone (ITZ) and inferior strength properties. It was found that incorporating a basalt fiber content of 4 kg/m3 could achieve a balance between the mechanical and physical properties of pervious concrete, which was suitable for structural applications.

To promote the in-situ and structural application of waste concrete in cold regions, the sustainable application potential of waste concrete in a freeze-thaw (F-T) environment was comprehensively evaluated from three aspects of performance, environmental load, and economic benefit. The recycled aggregate concrete (RAC) was produced by recycled coarse aggregate (RCA), which was obtained from the crushing of natural aggregate concrete (NAC) after every F-T 150 cycles until F-T failure. The effects of F-T damage of parent concrete on the physical properties of RCA and mechanical and frost resistance of RAC under 35% flexural stress were studied. Besides, the sustainability of NAC and RAC was compared and analyzed by emergy theory. The results suggested that the physical properties of RCA deteriorated gradually with the accumulation of F-T damage to parent concrete. The RCA obtained from parent concrete that suffered F-T damage could be used as coarse aggregate for structural concrete when F-T damage is smaller than 0.367. The F-T damage of parent concrete had an adverse effect on the mechanical properties and frost resistance of RAC. The frost resistance of RAC obtained from parent concrete with larger F-T damage was worse. The RAC prepared from parent concrete without F-T failure can serve 50 years in cold regions, while that with F-T failure can only serve 30 years. The F-T damage microelements were dispersed in the adhesive mortar of RCA and transferred to RAC, resulting in the reduction of the mechanical properties and frost resistance of RAC. Emergy analysis showed that the reuse of waste concrete after F-T failure required higher economic input, higher environment load, lower output efficiency, and sustainability. The performance, environmental load and economic benefit of RAC prepared by using waste concrete after F-T failure were inferior to that of waste concrete without F-T failure. Waste concrete after F-T failure is not recommended to be used as coarse aggregate for structural concrete.

Spermatogenesis, sperm motility, and apoptosis are dependent on the regulation of glandular hormones and mitochondria. Natural astaxanthin (ASTA) has antioxidant, anti-inflammatory, and anti-apoptotic properties. The present study evaluates the effects of ASTA on testosterone synthesis and mitochondrial function in aging roosters. Jinghong No. 1 layer breeder roosters (n = 96, 53-week old) were fed a corn–soybean meal basal diet containing 0, 25, 50, or 100 mg/kg ASTA for 6 weeks. The levels of plasma reproductive hormones and the mRNA and protein levels of molecules related to testosterone synthesis were significantly improved (p < 0.05) in the testes of the ASTA group roosters. In addition, antioxidant activities and free radical scavenging abilities in roosters of the ASTA groups were higher than those of the control group (p < 0.05). Mitochondrial electron transport chain complexes activities and mitochondrial membrane potential in sperm increased linearly with dietary ASTA supplementation (p < 0.05). The levels of reactive oxygen species and apoptosis factors decreased in roosters of the ASTA groups (p < 0.05). Collectively, these results suggest that dietary ASTA may improve testosterone levels and reduce sperm apoptosis, which may be related to the upregulation of the testosterone synthesis pathway and the enhancement of mitochondrial function in aging roosters.

Walnut (Juglans regia L.) is an important nut fruit crop mainly grown for its high nutritional and medicinal value. In walnut fruit, the pellicle is the main source of polyphenols (such as proanthocyanidins), which are natural bioactive compounds but also cause astringency and bitterness for walnut fruit consumption. However, the gene regulatory networks of phenolic biosynthetic pathways remain largely unknown in walnut pellicles. Here, we performed RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs) associated with pellicle development in walnut. In this study, seven developmental stages (8-, 9-, 11-, 13-, 15-, 17-, and 19-week after pollination) of ‘Xinwen179’ pellicle tissues were harvested to conduct further transcriptome-wide profiles. Via RNA-seq, we explored several key DEGs involved in the phenolic biosynthetic pathway, such as dihydroflavonol-4-reductase (DFR), leucoanthocyanidin reductase (LAR), anthocyanidin synthase (ANS) and anthocyanidin reductase (ANR), which are dynamically expressed at developmental stages of the walnut pellicle. Among them, ANR may directly contribute to proanthocyanidins accumulation during walnut development. Taken together, our preliminary investigation on DEGs associated with pellicle development will not only elucidate the gene regulatory networks of the phenolic biosynthetic pathway for pellicle development, but also contribute to the broad spectrum of RNA-seq data resources for further genetic improvement of walnut.

A numerical model of 84 high-strength concrete-filled square steel tubular columns (HSCFST) with local defects is developed using ABAQUS. The effects of parameters such as crack angle, crack length, impact surface and impact energy on the impact resistance of HSCFST columns are considered. The results show that under the effect of local corrosion, a model with horizontal cracks will show the phenomenon of crack closure when subjected to the front impact. The impact force platform value is mainly affected by the impact surface, followed by the crack angle, while the increase of the crack length mainly has a greater effect on the model of the rear impact. The impact resistance of the front impact model is better than that of the side and rear impact models. Increasing the crack length and decreasing the crack angle will increase the mid-span deflection of the model, and the mid-span deflection of the front impact model is smaller than that of the side and rear impact models. The energy absorption ratio of the model is proportional to the increase of the crack length and inversely proportional to the increase of the crack angle. Decreasing the crack angle will reduce the increase coefficient (Rd) of the dynamic flexural capacity of the model. A practical calculation method for the increased coefficient of the dynamic flexural capacity of HSCFST columns under local corrosion is proposed.

In this work, we conducted downward evacuation experiments in four types of staircases under various smoke visibility conditions of the naked eye, wearing sunglass and wearing eyeshades. Ten male and ten female college students were recruited to conduct the evacuation as a single male, single female, two males supporting one another, two females supporting one another and one male carrying another on his back. The evacuation time on each floor was recorded. The corresponding evacuation models were established by Pathfinder and verified against the test data. The effects of evacuation crowd density and response time considering gender factors on the evacuation time were simulated using the models. The results show that under the experimental condition of low visibility, the curve of evacuation time presents a stable state, whose change with the increase in the floors is not obvious. The increase in the evacuation time under different visibility indicates that males have better adaptability to the environment than females. The curves of SSP (straight running stairs with platform) and DSS (double split parallel stairs) are smoother than those of DPS (double running parallel stairs) and CS (corner stairs), indicating less pressure and less congestion during evacuation. During the emergency evacuation, the crowd pressure on the platform of the staircases is small. The front section of the flight and the corner part of the staircases are prone to congestion during evacuation. Under the influence of gender factors, since the response time of males is longer than that of females, the smaller the proportion of males, the smaller the time growth rate considering the reaction time. With the increase in crowd density, the effect of response time on total evacuation time becomes smaller.

Background: Increasing evidence indicates that vitamin D deficiency negatively affects the cardiovascular system. Here we studied the therapeutic effects of calcitriol in myocardial infarction (MI) and investigated its underlying mechanisms. Methods: A MI model of Kun-ming mice induced by left anterior descending coronary artery ligation was utilized to study the potential therapeutic effects of calcitriol on MI. AC16 human cardiomyocyte-like cells treated with TNF-α were used for exploring the mechanisms that underlie the cardioprotective effects of calcitriol. Results: We observed that calcitriol reversed adverse cardiovascular function and cardiac remodeling in post-MI mice. Mechanistically, calcitriol suppressed MI-induced cardiac inflammation, ameliorated cardiomyocyte death, and promoted cardiomyocyte proliferation. Specifically, calcitriol exerted these cellular effects by upregulating Vitamin D receptor (VDR). Increased VDR directly interacted with p65 and retained p65 in cytoplasm, thereby dampening NF-κB signaling and suppressing inflammation. Moreover, up-regulated VDR was translocated into nuclei where it directly bound to IL-10 gene promoters to activate IL-10 gene transcription, further inhibiting inflammation. Conclusion: We provide new insights into the cellular and molecular mechanisms underlying the cardioprotective effects of calcitriol, and we present comprehensive evidence to support the preventive and therapeutic effects of calcitriol on MI.