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Abstract Objective Human placenta-derived exosomes (pExo) were generated, characterized, and evaluated as a therapeutic candidate for the treatment of osteoarthritis (OA). Methods pExo was generated from full-term human placenta tissues by sequential centrifugation, purification, and sterile filtration. Upon analysis of particle size, cytokine composition, and exosome marker expression, pExo was further tested in cell-based assays to examine its effects on human chondrocytes. In vivo therapeutic efficacies were evaluated in a medial meniscal tear/medial collateral ligament tear (MCLT + MMT) rat model, in which animals received pExo injections intraarticularly and weight bearing tests during in-life stage while histopathology and immunohistochemistry were performed as terminal endpoints. Results pExo displayed typical particle size, expressed maker proteins of exosome, and contained proteins with pro-proliferative, pro-anabolic, anti-catabolic, or anti-inflammatory activities. In vitro, pExo promoted chondrocyte migration and proliferation dose-dependently, which may involve its activation of cell growth-related signaling pathways. Expression of inflammatory and catabolic genes induced in a cellular OA model was significantly suppressed by pExo. In the rat OA model, pExo alleviated pain burden, restored cartilage degeneration, and downregulated expressions of pro-inflammatory, catabolic, or apoptotic proteins in a dose-dependent manner. Conclusions Our study demonstrates that pExo has multiple potential therapeutic effects including symptom control and disease modifying characteristics. This may make it an attractive candidate for further development as an anti-OA therapeutic.

Many insects, including green lacewings, migrate seasonally to exploit suitable breeding and winter habitats. Green lacewings are important natural enemies of insect pests worldwide. Here, four dominant green lacewing species, Chrysoperla nipponensis (Okamoto), Chrysopa pallens (Rambur), Chrysoperla furcifera (Okamoto), and Chrysopa formosa Brauer, were investigated for their ability to migrate between northern and northeastern China across the Bohai Strait from late May to late October each year. Furthermore, there were significant interannual and seasonal differences in the number of migratory green lacewings collected. The number of green lacewings in spring was significantly lower than that in summer and autumn, and the highest average number of green lacewings occurred in June. In addition, there were differences in the sex ratio of migrating green lacewings between months, with a greater proportion of females than males. Finally, the seasonal migration trajectories simulated by the HYSPLIT model revealed that the green lacewings captured on Beihuang Island primarily originated from Shandong Province. Accordingly, these findings contribute to our understanding of green lacewing migration in eastern Asia and aid its incorporation within integrated pest management (IPM) packages for several crop pests. Furthermore, long-term tracking of migrant insect populations can reveal ecosystem services and trophic dynamic processes at the macroscale.

The development of rapid detection tools for viruses is vital for the prevention of pandemics and biothreats. Aptamers that target inactivated viruses are attractive for sensors due to their improved biosafety. Here, we evaluated a DNA aptamer (named as 6.9) that specifically binds to the inactivated SARS-CoV-2 virus with a low dissociation constant (KD = 9.6 nM) for the first time. Based on aptamer 6.9, we developed a fiber-optic evanescent wave (FOEW) biosensor. Inactivated SARS-CoV-2 and the Cy5.5-tagged short complementary strand competitively bound with the aptamer immobilized on the surface of the sensor. The detection of the inactivated SARS-CoV-2 virus was realized within six minutes with a limit of detection (LOD, S/N = 3) of 740 fg/mL. We also developed an electrochemical impedance aptasensor which exhibited an LOD of 5.1 fg/mL and high specificity. We further demonstrated that the LODs of the FOEW and electrochemical impedance aptasensors were, respectively, more than 1000 and 100,000 times lower than those of commercial colloidal gold test strips. We foresee that the facile aptamer isolation process and sensor design can be easily extended for the detection of other inactivated viruses.

Abstract Background Anti-thymoglobulin (ATG)-based immunosuppressive treatment (IST) is the standard first-line management for patients with severe AA/very severe AA (SAA/VSAA) and is not suitable for allogeneic stem cell transplantation. The response predictor was not fully investigated. Objective The present study attempted to explore other characteristics, such as serum lipid changes, during ATG-based IST and analyzed their significance in predicting IST response and survival. Methods A total of 61 newly diagnosed SAA/VSAA patients who received ATG-based IST were enrolled from January 2011 to June 2019. The blood lipid levels, immunoglobulins, and peripheral T lymphocytes were retrospectively collected, and their correlations with IST response, estimated 8.5-year overall survival (OS) and event-free survival (EFS) were analyzed. Results The overall response (OR)/complete remission (CR) at 3, 6, and 9 months was 24.6%/6.6%, 52.5%/14.8%, and 65.6%/23.0%, respectively. Based on the 9-month response effect, patients were divided into IST-response (IST-R) and IST-nonresponse (IST-NR) groups. The subgroup baseline characteristics showed that the disease severity grade, absolute neutrophil granulocyte count (ANC), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein-A (Apo-A) differed between the IST-R and IST-NR groups. Patients with lower Apo-A (

Abstract Background Spinal cord ischemia reperfusion injury (SCIRI) is a complication of aortic aneurysm repair or spinal cord surgery that is associated with permanent neurological deficits. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been shown to be potential therapeutic options for improving motor functions after SCIRI. Due to their easy access and multi-directional differentiation potential, adipose‐derived stem cells (ADSCs) are preferable for this application. However, the effects of ADSC-derived sEVs (ADSC-sEVs) on SCIRI have not been reported. Results We found that ADSC-sEVs inhibited SCIRI-induced neuronal apoptosis, degradation of tight junction proteins and suppressed endoplasmic reticulum (ER) stress. However, in the presence of the ER stress inducer, tunicamycin, its anti-apoptotic and blood–spinal cord barrier (BSCB) protective effects were significantly reversed. We found that ADSC-sEVs contain tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) whose overexpression inhibited ER stress in vivo by modulating the PI3K/AKT pathway. Conclusions ADSC-sEVs inhibit neuronal apoptosis and BSCB disruption in SCIRI by transmitting TSG-6, which suppresses ER stress by modulating the PI3K/AKT pathway.

With the increasingly extensive application of road engineering, it is inevitable to consider the durability of pavement in harsh environment. In the southeast coastal areas, northwest salt lakes and saline soil areas of China, harsh natural climate conditions and enhanced salt have a significant negative impact on the service life of asphalt pavements. In addition, the durability of asphalt pavement has suffered irreparable harm of the man-made salt environment. In this paper, five typical salt environment characteristics of asphalt pavement has been analyzed. The experimental conditions affecting the durability of asphalt concrete are determined. Then the durability deterioration mechanism of asphalt concrete is discussed under the coupling action of salt and multiple factors. Subsequently, the evaluation methods of asphalt concrete are categorized and summarized using scales for road performance and structure. Finally, according to the degree of salt erosion damage of asphalt concrete, a series of measures to alleviate salt erosion are proposed. The results show that the performance of asphalt concrete suffers significantly in salt environment, and the cohesion of asphalt and the adhesion of asphalt-aggregate interface are key factors in the durability of asphalt concrete. It has beneficial theoretical and practical significance for improving the durability of asphalt concrete under harsh natural environment.

Influenza A virus (IAV) infections are associated with a high healthcare burden around the world and there is an urgent need to develop more effective therapies. Natural killer (NK) cells have been shown to play a pivotal role in reducing IAV-induced pulmonary infections in preclinical models; however, little is known about the therapeutic potential of adoptively transferred NK cells for IAV infections. Here, we investigated the effects of CYNK-001, human placental hematopoietic stem cell derived NK cells that exhibited strong cytolytic activity against a range of malignant cells and expressed high levels of activating receptors, against IAV infections. In a severe IAV-induced acute lung injury model, mice treated with CYNK-001 showed a milder body weight loss and clinical symptoms, which led to a delayed onset of mortality, thus demonstrating their antiviral protection in vivo. Analysis of bronchoalveolar lavage fluid (BALF) revealed that CYNK-001 reduced proinflammatory cytokines and chemokines highlighting CYNK-001’s anti-inflammatory actions in viral induced-lung injury. Furthermore, CYNK-001-treated mice had altered immune responses to IAV with reduced number of neutrophils in BALF yet increased number of CD8+ T cells in the BALF and lung compared to vehicle-treated mice. Our results demonstrate that CYNK-001 displays protective functions against IAV via its anti-inflammatory and immunomodulating activities, which leads to alleviation of disease burden and progression in a severe IAV-infected mice model. The potential of adoptive NK therapy for IAV infections warrants clinical investigation.

The role of N6-methyladenosine modification in immunity is increasingly being appreciated. However, the landscape of m6A regulators in juvenile idiopathic arthritis (JIA) is poorly understood. Thus, this study explored the impact of m6A modification and related lncRNAs in JIA immune microenvironment. Fourteen m6A regulators and eight lncRNAs were identified as potential diagnostic biomarkers for JIA. Two diagnostic models for JIA were also constructed. The putative molecular regulatory mechanism of FTO-mediated m6A modification in JIA was hypothesized. Three distinct m6A patterns mediated by 26 m6A regulators and three diverse lncRNA clusters mediated by 405 lncRNAs were thoroughly investigated. They exhibited dramatically diverse immune microenvironments and expression of HLA genes. The identification of two separate subtypes of enthesitis-related arthritis implies that our work may aid in the establishment of a more precise categorization system for JIA. m6A modification-related genes were obtained, and their underlying biological functions were explored. The m6Ascore system developed for individual JIA patients may be utilized to evaluate the immunological state or molecular pattern, thereby offering therapy recommendations. In short, through the investigation of the m6A regulators in JIA, the current work may contribute to our knowledge of the pathophysiology of JIA.

Osteosarcoma (OS) is a malignant bone tumor that mainly occurs in adolescents. It is accompanied by a high rate of lung metastasis, and high mortality. Recent studies have suggested the important roles of tripartite motif-containing (TRIM) family proteins in regulating various substrates and signaling pathways in different tumors. However, the detailed functional role of TRIM family proteins in the progression of OS is still unknown and requires further investigations. In this study, we found that tripartite motif-containing 22 (TRIM22) was downregulated in OS tissues and was hence associated with better prognosis. In vitro and in vivo functional analysis demonstrated that TRIM22 inhibits proliferation and metastasis of OS cells. Nuclear factor erythroid 2-related factor 2 (NRF2), a redox regulator, was identified as a novel target for TRIM22. TRIM22 interacts with and accelerates the degradation of NRF2 by inducing its ubiquitination dependent on its E3 ligase activity but independent of Kelch-like ECH-associated protein 1 (KEAP1). Further, a series of gain- and loss-of-function experiments showed that knockdown or overexpression of NRF2 reversed the functions of knockdown or overexpression of TRIM22 in OS. Mechanistically, TRIM22 inhibited OS progression through NRF2-mediated intracellular reactive oxygen species (ROS) imbalance. ROS production was significantly promoted and mitochondrial potential was remarkably inhibited when overexpressing TRIM22, thus activating AMPK/mTOR signaling. Moreover, TRIM22 was also found to inhibit Warburg effect in OS cells. Autophagy activation was found in OS cells which were overexpressed TRIM22, thus leading to autophagic cell death. Treatment with N-Acetylcysteine (NAC), a ROS scavenger or the autophagy inhibitor 3-Methyladenine (3-MA) abolished the decreased malignant phenotypes in TRIM22 overexpressing OS cells. In conclusion, our study indicated that TRIM22 inhibits OS progression by promoting proteasomal degradation of NRF2 independent of KEAP1, thereby activating ROS/AMPK/mTOR/Autophagy signaling that leads to autophagic cell death in OS. Therefore, our findings indicated that targeting TRIM22/NRF2 could be a promising therapeutic target for treating OS.

The rapid growth of traffic load and volume has put forward higher requirements for road durability. To extend the service life of roads, this work investigated the feasibility of using polyolefin elastomers with a two-phase molecular structure to simultaneously improve the high and low-temperature performance of asphalt. The characteristics of the polyolefin modifier were evaluated by differential scanning calorimetry first. Following evaluation, the storage stability, workability, and rheological properties of modified polyolefin-modified asphalt were measured through softening point difference, rotary viscosity, dynamic shear rheometer, and bending beam rheometer. Additionally, the engineering performance of modified asphalt mixtures was also investigated through Marshall stability, wheel-tracking, and three points bending experiments. The results show that polyolefin has two glass transition points which facilitate the simultaneous improvement of the high and low-temperature properties of asphalt. Meanwhile, no concerns are found about the storage stability and workability of polyolefin-modified asphalt. Furthermore, the results of rheological properties indicate that polyolefin can significantly enhance the deformation resistance at high-temperature and cracking resistance at low-temperature of asphalt binders. While the fatigue performance of the polyolefin-modified asphalt is slightly reduced, the residual Marshall stability, dynamic stability, and ultimate tensile strain of the asphalt mixture containing 8% polyolefin are 1.05 times, 1.31 times, and 1.17 times those of the control sample, respectively. The results of infrared spectroscopy demonstrate that there is no chemical reaction between the polyolefin-modified and the virgin asphalt. The improvement of polyolefin on asphalt performance can be explained by the existence of both “rigid” and “flexible” structures in polyolefin.

Abstract The high‐pressure gas expansion‐induced deformation and dynamic fracture of coal are important parts of coal and gas outburst. To better understand the law of this process, laboratory experiments and numerical simulation are used to study the law of damage. A cavity with different pressures of CH4 or N2 was destroyed by a jack to achieve the rapid expansion of the gas and coal fracture inside. The particle size distribution of the coal particles before and after the experiment was measured, and the breakage ratio and the newly added surface area were calculated. The experimental results indicate that during the gas expansion process, the breakage ratio of coal and the newly added surface area clearly increase with the increase in gas pressure. Finally, a numerical model based on peridynamic theory was developed to simulate crack generation and the propagation of coal induced by the expansion of gases at different pressures. The numerical simulation results show that the higher the initial gas pressure is, the higher the number of failure units. Moreover, only when the gas pressure is large enough will the coal crack in various directions at the same time.

Abstract Background Colorectal cancer (CRC) is one of the most common malignancies, and it’s expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism. Methods Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway. Results Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such as MYC and JUN. Conclusions These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.

Abstract Gas distribution ahead of the coal tunnel is the key risk factor controlling coal and gas outburst. Based on an analysis of the influence of the stress state on the porosity of the coal seam, an improved quartet structure generation set (QSGS) random porous media generation tool is used to reconstruct the coal structure. Adopting the reconstructed pore structure of the coal as the boundary of the flow field, the Lattice Boltzmann method (LBM) is used to simulate the gas dynamic distribution law ahead of the coal tunnel. The gas pressure of the coal seam decreases obviously in the fracture zone only, and the change in gas pressure is very small in the stress concentration zone and ahead of the coal seam. This research is of significance for gas drainage and the prevention of coal and gas outburst hazards in the working face during coal tunneling.

Lycopene is an important natural red pigment with strong singlet oxygen and peroxide free radical quenching ability. Ethanol directly destroys the epithelial cells of gastric mucosa, causing oxidative damage and inflammation. To evaluate the effect of lycopene on the ethanol induced gastric injury, 112 adult male Kunming mice were randomly divided into normal control, lycopene control, gastric injury control, omeprazole (20 mg/kg) positive control, and lycopene experimental groups (at doses of 10, 50, 100, and 150 mg/kg body weight) in this study. The general and pathological evaluation, gastric secretion, as well as the levels of antioxidant and inflammatory factors were detected. In lycopene experimental groups, the amount of gastric juice were lower than that in the gastric injury control group; the levels of T-SOD, and the levels of MDA and inflammatory factors (MMP-9 and MCP-1) decreased. However, general and pathological evaluation of gastric tissues revealed that lycopene (especially at high doses) could aggravate acute gastric mucosal injury induced by ethanol. Therefore, lycopene (especially at high doses) aggravates acute gastric mucosal injury caused by ethanol, but this was not due to oxidative stress or inflammatory factors. In lycopene control group, the levels of MTL, T-SOD, and NO increased, but the levels of ALT and AST decreased, indicating that lycopene has a protective effect on the stomach and liver when ethanol wasn't taken. It reminds us that, when alcohol is consumed in large quantities, consumption of lycopene products should be carefully considered.

We previously determined that the cyclase inhibitor tripropylamine (TPA) significantly enhances lycopene accumulation in Blakeslea trispora. To elucidate the mechanism of TPA-enhanced lycopene accumulation, the untargeted metabolome of B. trispora treated with TPA was analyzed by UHPLC-Q-TOF/MS. Forty-two differential metabolites were identified, of which 15 significantly differential metabolites meeting the following parameters were screened: variable importance for the projection > 1, P < 0.05, and fold change > 1.5. The down-regulated metabolites were mainly cyclic dipeptides, bacteriostatic compounds, and lipids, while the up-regulated metabolites were mainly unsaturated fatty acid. Furthermore, the bacteriostatic ability was poor, the extracellular and intracellular pH levels were high, and hyphae with vesicles were swollen locally in B. trispora after treatment with TPA. Our data suggest that the TPA enhances lycopene accumulation not only by inhibiting the cyclization of β-carotene but also by down-regulating cyclic dipeptides for quorum sensing; up-regulating unsaturated fatty acids, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine, and 4-hydroxybenzoate and down-regulating choline, resulting in locally swelling mycelium with vacuoles; and down-regulating bacteriostatic metabolites for metabolic flux redistribution.

Abstract Background TP53 is one of the most frequently mutated genes among all cancer types, and TP53 mutants occur more than 60% in colorectal cancer (CRC). Among all mutants, there are three hot spots, including p53-R175H, p53-R248W and p53-R273H. Emerging evidence attributes cancer carcinogenesis to cancer stem cells (CSCs). Long noncoding RNAs (lncRNAs) play crucial roles in maintaining the stemness of CSCs. However, it is unknown if mutant p53-regulated lncRNAs are implicated in the maintenance of CSC stemness. Methods RNA-sequencing (RNA-seq) and ChIP-sequencing (ChIP-seq) were used to trace the lncRNA network regulated by p53-R273H in HCT116 endogenous p53 point mutant spheroid cells generated by the somatic cell knock-in method. RT-qPCR was used to detect lncRNA expression patterns, verifying the bioinformatics analysis. Transwell, spheroid formation, fluorescence activated cell sorter (FACS), xenograft nude mouse model, tumor frequency assessed by extreme limiting dilution analysis (ELDA), Western blot assays and chemoresistance analysis were performed to elucidate the functions and possible mechanism of lnc273–31 and lnc273–34 in cancer stem cells. Results p53-R273H exhibited more characteristics of CSC than p53-R175H and p53-R248W. RNA-seq profiling identified 37 up regulated and 4 down regulated differentially expressed lncRNAs regulated by p53-R273H. Combined with ChIP-seq profiling, we further verified two lncRNAs, named as lnc273–31 and lnc273–34, were essential in the maintenance of CSC stemness. Further investigation illustrated that lnc273–31 or lnc273–34 depletion dramatically diminished colorectal cancer migration, invasion, cancer stem cell self-renewal and chemoresistance in vitro. Moreover, the absence of lnc273–31 or lnc273–34 dramatically delayed cancer initiation and tumorigenic cell frequency in vivo. Also, lnc273–31 and lnc273–34 have an impact on epithelial-to mesenchymal transition (EMT). Finally, lnc273–31 and lnc273–34 were significantly highly expressed in CRC tissues with p53-R273H mutation compared to those with wildtype p53. Conclusions The present study unveiled a high-confidence set of lncRNAs regulated by p53-R273H specific in colorectal CSCs. Furthermore, we demonstrated that two of them, lnc273–31 and lnc273–34, were required for colorectal CSC self-renewal, tumor propagation and chemoresistance. Also, the expression of these two lncRNAs augmented in colorectal cancer patient samples with p53-R273H mutation. These two lncRNAs may serve as promising predictors for patients with p53-R273H mutation and are vital for chemotherapy.

Abstract Background Our previous work revealed that rhomboid domain-containing protein 1 (RHBDD1) participates in the modulation of cell growth and apoptosis in colorectal cancer cells. This study aimed to investigate the function of RHBDD1 in regulating breast cancer progression and its underlying molecular basis. Methods Immunohistochemistry was performed to evaluate RHBDD1 expression in 116 breast cancer tissue and 39 adjacent normal tissue and expression of RHBDD1, phospho-Akt (p-Akt) and cyclin-dependent kinase 2 (CDK2) in the same 84 breast cancer specimens. RHBDD1-knock-out cells were established using breast cancer cell lines. In vitro studies were carried out to estimate the function of RHBDD1 in cell proliferation, migration and invasion. Fluorescence microscopy assay and flow cytometric analysis were used to measure apoptosis and cell cycle regulation. RNA sequencing and western blot analysis were used to investigate the molecular mechanisms of RHBDD1. Results RHBDD1 was highly up-regulated in breast cancer tissue compared with that in normal tissue and associated with pathological tumor (pT) stage, pathological tumor-node-metastasis (pTNM) stage and estrogen receptor (ER) expression. RHBDD1 up-regulation was associated with poor prognosis in several subtypes of breast cancer. Deletion of RHBDD1 promoted apoptosis and suppressed proliferation, migration and invasion in breast cancer cells. RHBDD1 deletion suppressed Akt activation and decreased CDK2 protein level via proteasome pathway, thus inhibited cell cycle progression and G1/S phase transition. Moreover, the protein level of RHBDD1, p-Akt and CDK2 was significantly positively correlated in breast cancer tissue. Conclusions Our study reveals that RHBDD1 promotes breast cancer progression by regulating p-Akt and CDK2 protein levels, and might be a potential biomarker and prognostic indicator for breast cancer patients.

The lattice Boltzmann method (LBM) and large-eddy simulation (LES) are combined with a scalar subgrid-scale model to simulate the indoor air velocity field and harmful gas dispersion. The LBM-LES model is validated by comparing its results with published experimental and numerical simulation results. Taking a simplified chemical building as the scenario, the relative ventilation efficiency is evaluated based on the maximum harmful gas concentration, and configurations with centralized and distributed harmful gas sources with both mixing ventilation (MV) and displacement ventilation (DV) systems are considered. According to the results, if the density of the harmful gas is less than the air density, the DV system is more efficient than the MV system. The DV system is more stable than the MV system under fluctuating relative ventilation efficiency due to changes in the distance between the ventilation vents and in the distance between the centralized gas sources and the exhaust air vent.

Applying basic oxygen furnace (BOF) slag as aggregate in asphalt mixture is continuously investigated due to the increasing shortage of natural aggregate in recent years. However, the negative effect of BOF’s expansion in water greatly limits its further application in pavement construction. To address this problem, this paper studied the volume stability of BOF, and its asphalt mixture relied on actual engineering. The asphalt mixtures contained BOF aggregate was designed by the Marshall method with three different gradation types (AC-16, AC-20, and ATB-25). Besides, both laboratory samples and the core samples from field drilling were investigated in volume expansion rate after curing in a water bath. The economic and resource benefits of BOF replacement of natural aggregates were also analyzed. The results showed that the free calcium oxide content of BOF slag is positively related to the particle sizes. Nevertheless, the expansion rates of both the BOF aggregate and its asphalt mixture were less than 1%, which meant the BOF aggregate applied to the asphalt mixture meets the practical engineering requirements. The maximum allowable free calcium oxide content for large-grain size of steel slag is the smallest; it is also recommended that the expansibility of large-grain steel slag should be the first concern in the application. The resource assessment indicated that the use of steel slag for the construction of a trial section of one kilometer of single lane can save 967 tons of natural aggregates. The economic evaluation showed that the use of steel slag instead of natural aggregates for surface course construction could reduce the investment by 16.87%. The experimental methods and conclusions mentioned in this article provide stable references to enhance the development of sustainable pavement by recycling metallurgical slag in highway construction.

To meet the demand of ship control, a new heading control tactic is explored using switching theory. Different from the previous results, the stochastic noise and switched control are considered in the Norrbin nonlinear mathematical model concurrently to discuss ship heading control. Then, for the resulting systems, the adaptive control issue is addressed, while the dead-zone input is embedded and unknown. By establishing switched state observers for the corresponding subsystems, the conservatism of the common state observer can be reduced greatly, and the analysis can be achieved under the switching signal satisfying the average dwell time (ADT). The “explosion of terms” problem occurring in the backstepping technique is well remedied via an innovative tracking differentiator (TD) technology, which is an innovation in itself. According to the theory proof, under the developed control tactic, the resulting signals are then to be bounded in probability, with the tracking goal being achieved well. The theoretical design result was analyzed, and the corresponding validity is given through simulation experiments.

Abstract Background 40–50% of colorectal cancer (CRC) patients develop metastatic disease; the presence of metastasis hinders the effective treatment of cancer through surgery, chemotherapy and radiotherapy, which makes 5-year survival rate extremely low; therefore, studying CRC metastasis is crucial for disease therapy. In the present study, we investigated the role of rhomboid domain containing 1 (RHBDD1) in tumor metastasis of CRC. Methods The expression of RHBDD1 was analyzed in 539 colorectal tumor tissues for its correlation with lymphatic metastasis and distal metastasis. Transwell assay in vitro and pleural metastasis analysis in vivo were performed to determine the functions of RHBDD1 during CRC cells metastasis. RNA-seq analysis, TOP/FOP flash reporter assay, western blot and transwell assay were performed to investigate the underlying mechanism for the function of RHBDD1 on Wnt signaling pathway. Bioinformatics analysis was conducted to investigate epithelial-mesenchymal transition (EMT) and stemness in HCT-116 cells. Tissue microarray analysis, Q-PCR and western blot were performed to determine the correlation of RHBDD1 and Zinc Finger E-Box Binding Homeobox 1 (ZEB1). Results In this study, we found that RHBDD1 expression was positively correlated with lymphatic metastasis and distal metastasis in 539 colorectal tumor tissues. RHBDD1 expression can promote CRC cells metastasis in vitro and in vivo. RNA-Seq analysis showed that the Wnt signaling pathway played a key role in this metastatic regulation. RHBDD1 mainly regulated ser552 and ser675 phosphorylation of β-catenin to activate the Wnt signaling pathway. Rescuing ser552 and ser675 phosphorylation of β-catenin resulted in the recovery of signaling pathway activity, migration, and invasion in CRC cells. RHBDD1 promoted EMT and a stem-like phenotype of CRC cells. RHBDD1 regulated the Wnt/β-catenin target gene ZEB1, a potent EMT activator, at the RNA and protein levels. Clinically, RHBDD1 expression was positively correlated with ZEB1 at the protein level in 71 colon tumor tissues. Conclusions Our findings therefore indicated that RHBDD1 can promote CRC metastasis through the Wnt signaling pathway and ZEB1. RHBDD1 may become a new therapeutic target or clinical biomarker for metastatic CRC.

Laboratory-synthesized specimens are employed for an experimental study on the mechanical properties of hydrate-bearing sediments (HBS) due to the difficulty of field coring. A representative synthesized sample for the analysis of the mechanical properties of HBS in the experimental study requires evenly distributed hydrates in the pores of the sample. However, a specimen made with an improper sand–water mixing method might have an uneven water distribution, resulting in an uneven hydrate distribution when applying the ice-seeding method for hydrate formation. This study adopted three kinds of methods to mix sand and water before forming hydrates and applied the low-field nuclear magnetic resonance (NMR) technique to investigate how these methods affect the hydrate distribution, further affecting the mechanical properties. To analyze the mechanical properties of HBS, we conducted drained triaxial tests. As shown in low-field NMR, when we compacted a sample of the sand–water mixture and froze it upside-down before hydrate formation, a sample with an even water distribution was obtained. Subsequently, the hydrate in HBS distributed also evenly. The stress-strain curves present different strain softening and hardening patterns due to the different hydrate distributions. Moreover, the samples with the evenly distributed hydrates have higher initial elastic modulus and strength than the ones made with other methods.

An experiment designed to simulate coal during excavation was conducted. Microseismic signals of coal under vibration conditions during excavation and subsequent waiting time of the coal roadway at different excavation speeds were collected and analyzed. During the excavation and subsequent waiting time, the stress in coal is redistributed, and the concentrated stress is gradually transferred to the deeper section of the coal seam. The Hilbert–Huang transform (HHT) is used to effectively denoise the collected signals. According to the noise-reduced signal, the amplitude and pulse number of the microseismic signals emitted during the excavation process are much larger than those of the waiting time process. During excavation, the energy and event numbers of microseismic signals increase first and then decrease as the excavation speed increases. The faster the excavation speed, the more the energy, and the higher the event numbers of the microseismic signals released during the subsequent waiting time. When the excavation speed is faster, more elastic potential accumulates in the coal seam and the concentration stress is greater. As the concentrated stress moves forward in time without excavation, more coal seams fail, and more microseismic signals are released. The microseismic signal and the stress evolution law can provide a reasonable explanation for the forward movement of the concentrated stress and coal failure during roadway excavation.

To investigate the fracture characterizations of rocks under high strain rate tensile failure, a series of dynamic Brazilian tests was conducted using Split Hopkinson pressure bar (SHPB), and a high-speed digital camera at a frame rate of 50,000 frames per second (FPS) with a resolution of 272 × 512 pixels was adopted to capture the real-time images and visualize the failure processes. Using the extracted cracks and image processing technique, the relationship between loading condition (impact velocity), crack propagation process (crack velocity, crack fractal characteristic, and crack morphological features), and dynamic mechanical properties (absorbed energy and strain-stress parameters) was explored and analyzed. The experimental results indicate that (1) impact velocity plays a critical role in both crack propagation process and dynamic mechanical properties, (2) the crack fractal dimension is positively correlated with crack propagation velocity and has a linear relationship with the proposed morphological feature of crack, (3) mean strain rate and max strain of rocks under SHPB loading both decrease with the increase of crack propagation velocity, and (4) the energy absorbed by the rocks increases with increasing impact velocity and has a strong negative correlation with a proposed novel crack descriptor. Experimental studies pertaining to the measurement of crack propagation path and velocity, in particular, some crack feature extraction approaches, present a promising way to reveal the fracture process and failure mechanisms of rock-like materials.

Steel slag, a by-product of steelmaking, imposes lots of negative impacts on the environment. For alleviating negative impacts, more and more experiments have been carried out to explore the application possibility of steel slag. The purpose of this study is to explore the feasibility of steel slag being applied in induction healing asphalt concretes to replace coarse and fine aggregate. Surface texture and pore sizes of steel slag were firstly tested, and then steel slag and basalt asphalt mixtures modified with steel fibers were prepared. Moisture susceptibility, dynamic stability, mechanical property, thermal property, induction heating speed, natural cooling speed and healing property of the asphalt mixtures were evaluated. Results showed that steel slags had more obvious holes in the surface while the surface area is much larger than that of basalt. Furthermore, steel fibers and steel slag both have dynamic stability, and steel fibers contribute to increased moisture resistance while steel slag is not. Steel slag asphalt concrete showed better mechanical property and better capacity to store heating. Steel slag asphalt mixtures had a similar heating speed to basalt asphalt mixtures but a significantly slower cooling rate. Finally, the induction healing test and CT scanning test demonstrated that steel slag asphalt mixtures had a similar healing ability to basalt asphalt mixtures. It can be concluded that steel slags have the potential to replace the natural aggregates to be applied in induction heating self-healing asphalt concretes.

Gas adsorption occurs when the dynamic adsorption equilibrium conditions of the local adsorptive sites are broken. In the overall process of unconventional natural gas generation, enrichment, storage, and production, this phenomenon plays a significant role. A double-distribution Lattice Boltzmann model for solving the coupled generalized Navier-Stokes equation and advection-diffusion equation with respect to the gas-solid dynamic adsorption process is proposed for multicomponent gas migration in the unconventional reservoir. The effective diffusion coefficient is introduced to the model of gas transport in the porous media. The Langmuir adsorption rate equation is employed to control the adsorption kinetic process of gas-solid adsorption/desorption. The model is validated in two steps through fluid flow without and with gas diffusion-adsorption between two parallel plates filled with porous media, respectively. Simulation results indicate that with other parameters being equal, the rate of gas diffusion in the porous material and the area of the dynamic adsorption equilibrium-associated region increase with the matrix porosity/permeability. Similar results will happen with a greater saturation adsorption amount or a lower Langmuir pressure. The geometric effect on adsorption is also studied, and it is found that a higher specific surface area or free flow region can enhance the gas transport and the rate of adsorption.

Nanosecond laser ablated metallic surfaces showed initial super-hydrophilicity, and then experienced gradual wettability conversion to super-hydrophobicity with the increase of exposing time to ambient air. Due to the presence of hierarchical structures and change of surface chemistry, the laser-induced Inconel alloy surfaces showed a stable apparent contact angle beyond 150° over 30-day air exposure. The wetting states were proposed to elucidate the initial super-hydrophilicity and the final super-hydrophobicity. The basic fundaments behind the wettability conversion was explored by analyzing surface chemistry using X-ray photoelectron spectroscopy (XPS). The results indicated that the origins of super-hydrophobicity were identified as the increase of carbon content and the dominance of C–C(H) functional group. The C–C(H) bond with excellent nonpolarity derived from the chemisorbed airborne hydrocarbons, which resulted in dramatic reduction of surface-free-energy. This study confirmed that the surface chemistry is not the only factor to determine surface super-hydrophobicity. The laser-induced super-hydrophobicity was attributed to the synergistic effect of surface topography and surface chemical compositions. In this work, the corresponding chemical reaction was particularly described to discuss how the airborne hydrocarbons were attached onto the laser ablated surfaces, which reveals the generation mechanism of air-exposed super-hydrophobic surfaces.

Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.

T1 sagittal angle has been reported to be used as a parameter for assessing sagittal balance and cervical lordosis. However, no study has been performed to explore the relationship between T1 sagittal angle and sagittal balance, and whether T1 sagittal angle could be used for osteotomy guidelines remains unknown. The aim of our study is to explore the relationship between T1 sagittal angle and sagittal balance, determine the predictors for T1 sagittal angle, and determine whether T1 sagittal angle could be used for osteotomy guidelines to restore sagittal balance. Medical records of healthy volunteers in our outpatient clinic from January 2014 to August 2015 were reviewed, and their standing full-spine lateral radiographs were evaluated. Demographic and radiological parameters were collected and analyzed, including age, gender, T1 sagittal angle, maxTK, maxLL, SS, PT, and PI. Correlation coefficients between T1 sagittal angle and other spinopelvic parameters were determined. In addition, multiple regression analysis was performed to establish predictive radiographic parameters for T1 sagittal angle as the primary contributors. A total of 119 healthy volunteers were recruited in our study with a mean age of 34.7 years. It was found that T1 sagittal angle was correlated with maxTK with very good significance (r = 0.697, P

Abstract In the publication of this article [1], there is an error in the Methods section at paragraph Cell culture and reagents and the Additional file2: Fig. S1 was erroneous linked.