Search

Abstract Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

Background: Collagen represents a prominent constituent of the tumor’s extracellular matrix (ECM). Nonetheless, its correlation with the molecular subtype attributes of clear cell renal cell carcinoma (ccRCC) remains elusive. Our objective is to delineate collagen-associated molecular subtypes and further construct diagnostic model, offering insights conducive to the precise selection of ccRCC patients for immunotherapeutic interventions.Methods: We performed unsupervised non-negative matrix factorization (NMF) analysis on TCGA-KIRC samples, utilizing a set of 33 collagen-related differentially expressed genes (33CRDs) for clustering. Our analysis encompassed evaluations of subtype-associated differences in pathways, immune profiles, and somatic mutations. Through weighted gene co-expression network analysis (WGCNA) and four machine learning algorithms, two core genes were found and a diagnostic model was constructed. This was subsequently validated in a clinical immunotherapy cohort. Single cell sequencing analysis and experiments demonstrated the role of core genes in ccRCC. Finally, we also analyzed the roles of MMP9 and SCGN in pan-cancer.Results: We described two novel collagen related molecular subtypes in ccRCC, designated subtype 1 and subtype 2. Compared with subtype 1, subtype 2 showed more infiltration of immune components, but had a higher TIDE (tumor immunedysfunctionandexclusion) score and increased levels of immune checkpoint molecules. Furthermore, reduced prognosis for subtype 2 was a consistent finding in both high and low mutation load subgroups. MMP9 and SCGN were identified as key genes for distinguishing subtype 1 and subtype 2. The diagnostic model based on them could better distinguish the subtype of patients, and the differentiated patients had different progression free survival (PFS) in the clinical immunotherapy cohort. MMP9 was predominantly expressed in macrophages and has been extensively documented in the literature. Meanwhile, SCGN, which was overexpressed in tumor cells, underwent experimental validation, emphasizing its role in ccRCC. In various cancers, MMP9 and SCGN were associated with immune-related molecules and immune cells.Conclusion: Our study identifies two collagen-related molecular subtypes of ccRCC and constructs a diagnostic model to help select appropriate patients for immunotherapy.

Abstract The development of castration‐resistant prostate cancer (CRPC) is a significant factor that reduces life expectancy among patients with prostate cancer. Previously, it is reported that CDK4/6 inhibitors can overcome the resistance of CRPC to BET inhibitors by destabilizing BRD4, suggesting that the combination of CDK4/6 inhibitors and BET inhibitors is a promising approach for treating CRPC. In this study, candidates that affect the combined antitumor effect of CDK4/6 inhibitors and BET inhibitors on CRPC is aimed to examine. The data demonstrates that CBX3 is abnormally upregulated in CDK4/6 inhibitors‐resistant cells. CBX3 is almost positively correlated with the cell cycle in multiple malignancies and is downregulated by BET inhibitors. Mechanistically, it is showed that CBX3 is transcriptionally upregulated by BRD4 in CRPC cells. Moreover, it is demonstrated that CBX3 modulated the sensitivity of CRPC to CDK4/6 inhibitors by binding with RB1 to release E2F1. Furthermore, it is revealed that PLK1 phosphorylated CBX3 to enhance the interaction between RB1 and CBX3, and desensitize CRPC cells to CDK4/6 inhibitors. Given that BRD4 regulates CBX3 expression and PLK1 affects the binding between RB1 and CBX3, it is proposed that a dual BRD4/PLK1 inhibitor can increase the sensitivity of CRPC cells to CDK4/6 inhibitors partially through CBX3.

Interface debonding and slab end arching of the anchor-reinforced and coated longitudinally continuous slab tracks have been unprecedentedly investigated in this study. A novel finite element model of the longitudinally continuous slab track has been established by incorporating a tailored cohesive zone model to mimic nonlinear constitutive relationships. The new model has been validated by over 100 field measurement data. This paper is the first to assess the influences of the dual applications of anchors and coatings on the damages of the longitudinally continuous slab tracks, and to identify the effectiveness of different track maintenance methods in mitigating track damages. This study exhibits new findings: (1) In comparison with traditional tracks, the tracks constructed with anchors, coatings, and the combined use of both can reduce the maximum vertical relative displacement between the concrete slab and the mortar layer by 75%, 40%, and 85% respectively. (2) In comparison with 4 anchors, 6 or more anchors in each slab can help to prevent inner interface defects. However, an increase in anchor quantity above 6 anchors does not have a significant impact on the interface damage mitigation. (3) For the anchor-reinforced tracks, the organic coating outweighs the inorganic coating to improve interface damage mitigation.

Abstract Background This study aims to construct and verify a nomogram model for microvascular invasion (MVI) based on hepatocellular carcinoma (HCC) tumor characteristics and differential protein expressions, and explore the clinical application value of the prediction model. Methods The clinicopathological data of 200 HCC patients were collected and randomly divided into training set and validation set according to the ratio of 7:3. The correlation between MVI occurrence and primary disease, age, gender, tumor size, tumor stage, and immunohistochemical characteristics of 13 proteins, including GPC3, CK19 and vimentin, were statistically analyzed. Univariate and multivariate analyzes identified risk factors and independent risk factors, respectively. A nomogram model that can be used to predict the presence of MVI was subsequently constructed. Then, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were conducted to assess the performance of the model. Results Multivariate logistic regression analysis indicated that tumor size, GPC3, P53, RRM1, BRCA1, and ARG were independent risk factors for MVI. A nomogram was constructed based on the above six predictors. ROC curve, calibration, and DCA analysis demonstrated the good performance and the clinical application potential of the nomogram model. Conclusions The predictive model constructed based on the clinical characteristics of HCC tumors and differential protein expression patterns could be helpful to improve the accuracy of MVI diagnosis in HCC patients.

Abstract Intervertebral disc degeneration (IDD) has been identified as one of the predominant factors leading to persistent low back pain and disability in middle-aged and elderly people. Dysregulation of Prostaglandin E2 (PGE2) can cause IDD, while low-dose celecoxib can maintain PGE2 at the physiological level and activate the skeletal interoception. Here, as nano fibers have been extensively used in the treatment of IDD, novel polycaprolactone (PCL) nano fibers loaded with low-dose celecoxib were fabricated for IDD treatment. In vitro studies demonstrated that the nano fibers had the ability of releasing low-dose celecoxib slowly and sustainably and maintain PGE2. Meanwhile, in a puncture-induced rabbit IDD model, the nano fibers reversed IDD. Furthermore, low-dose celecoxib released from the nano fibers was firstly proved to promote CHSY3 expression. In a lumbar spine instability-induced mouse IDD model, low-dose celecoxib inhibited IDD in CHSY3wt mice rather than CHSY3−/− mice. This model indicated that CHSY3 was indispensable for low-dose celecoxib to alleviate IDD. In conclusion, this study developed a novel low-dose celecoxib-loaded PCL nano fibers to reverse IDD by maintaining PGE2 at the physiological level and promoting CHSY3 expression.

Abstract Preeclampsia (PE) is the most common medical complication during pregnancy and the second leading cause of maternal death worldwide. However, a better predictive model of PE remains to be explored. A total of 15 severe preeclampsia (sPE) and 75 healthy control patients were included in this study. Patient data was obtained from September 2019 to September 2021. Nuchal translucency (NT) and crown‐rump length (CRL) of the fetus were acquired by ultrasound. Maternal blood samples were collected at 11+0 to 13+6 weeks of gestation. Chemiluminescent immunoassays were used to detect serum testosterone (T) and estradiol (E2) levels. Time‐resolved fluorescence analysis was used to examine the levels of serum pregnancy‐associated plasma protein A (PAPPA) and β‐human chorionic gonadotrophin (β‐HCG) protein. The sPE group exhibited increased T levels, and decreased E2 levels and E2/T ratios from 11 to 14 weeks of gestation, compared with the control group. E2 and the E2/T ratio showed positive linear correlation with CRL in pregnant women. Body‐mass‐index (BMI), T, and E2 were determined to be the main factors that affected the occurrence of sPE at the 12‐week gestation period time point. The receiver operating characteristic (ROC) curve revealed that the AUC of the E2/T ratio was .717. The imbalanced T and E2 levels in the patients had a specific intrinsic relevance with sPE, which suggests them as novel predictors of the sPE.

In this paper, a robust adaptive unscented Kalman filter (RAUKF) is developed to mitigate the unfavorable effects derived from uncertainties in noise and in the model. To address these issues, a robust M-estimator is first utilized to update the measurement noise covariance. Next, to deal with the effects of model parameter errors while considering the computational complexity and real-time requirements of dynamic state estimation, an adaptive update method is produced. The proposed method is integrated with spherical simplex unscented transformation technology, and then a novel derivative-free filter is proposed to dynamically track the states of the power system against uncertainties. Finally, the effectiveness and robustness of the proposed method are demonstrated through extensive simulation experiments on an IEEE 39-bus test system. Compared with other methods, the proposed method can capture the dynamic characteristics of a synchronous generator more reliably.

Multi-heterogeneous energy (MHE) system includes both energy systems: regional-level and park-level. Energy hub station (EHS) is the energy interaction hub between regional-level energy system and park-level energy users. In order to achieve the multi-energy optimal dispatching, it is very essential to properly coordinate the lean modeling and fast solution of MHE system. In this paper, the component-level modeling and linearization method of MHE system is studied. Furthermore, an improved unified modeling and linearization method for energy hub station is proposed to obtain energy optimal dispatching. In the case study, 39-node power system and 20-node natural gas system are utilized as regional energy networks, and two energy hub stations are constructed as park-level energy hubs. Based on the hierarchical optimization structure, the simulation analysis is carried out. Compared with the nonlinear solution methods, the effectiveness of the proposed method is verified in terms of solution accuracy and calculation time.

The elastic cushion is mostly used between the layers of ballastless tracks laid on a large-span cable-stayed bridge with a main span of more than 300 m. The rubber material is easy to harden and age, the geotextile has good acid-alkali resistance and antiwear performance, and the feasibility of geotextile application on the large-span cable-stayed bridge can be explored. The coupling model of a long-span cable-stayed bridge and the ballastless track was established to analyze the longitudinal mechanical characteristics of the seamless line, the deformation of the track structure, and the separation of the track plate and base plate under different loads. The results show that the application of geotextile or elastic cushion has little effect on the longitudinal mechanical properties of seamless lines. Compared to the elastic cushion, laying the geotextile increases the longitudinal stress of the slab by 0.13 Mpa, 0.025 Mpa, and 0.06 Mpa under different types of loads. The strength calculation of the seamless track is within the safety range. Laying elastic cushion can restrain the generation of separation under vertical loads, but there is no effect laying elastic cushion under temperature loads and braking loads, and the height of separation was less than 0.4 mm. The stress and deformation of the ballastless track do not exceed the standard when applying geotextile; it is feasible to apply geotextile on ballastless tracks on a large-span cable-stayed bridge. The next step is to study the vehicle–bridge–track dynamic response when elastic cushion and geotextile are laid.

The stability of a 1000 mm/1435 mm dual-gauge track is lower than that of a single-gauge track. One of the important factors that affects the stability of the track is the lateral resistance of the track bed. We have established a discrete element simulation model of the dual-gauge sleeper-track bed in PFC to analyse the characteristics of the lateral resistance of the 1000 mm/1435 mm dual-gauge sleeper. With China Type IIIc sleepers as the control group, we carried out the lateral resistance test for the full-scale sleeper model under the same conditions. The research results indicate that the most effective way to increase the lateral resistance of the dual-gauge track bed is to increase the end surface area and bottom area of the sleeper. The application of adjacent sleepers is an effective way to increase the lateral resistance of the track bed further. The research results gained from this study can be used to guide the design of dual-gauge sleepers.

Diseases such as track slab arching and joint concrete crushing of China Railway Track System (CRTS)II slab track were caused by huge temperature force, which seriously threatens driving safety of trains. In this study, a longitudinal weak connection scheme of CRTSII slab track was proposed to adjust the temperature force in track slab and reduce diseases of longitudinal continuous track slab. This paper focuses on the cracking characteristics of the longitudinal heterogeneous concrete composite structure. The equation which was originally developed to calculate crack width and structure stress under temperature loads, was put forward to consider deformation difference of different elastic modulus. The influence law of various parameters was analyzed. The reinforcement stress and crack width of CRTSII slab track after longitudinal connection weakening were calculated, and the reasonable limit value of tensile force of connection reinforcement and the minimum value of bond resistance of reinforcement in joint position were obtained. The result shows that, in order to reduce the bond resistance between the joint material and the reinforcement, the elastic modulus of the elastic material should be less than 5000 MPa; in order to ensure that the reinforcement does not produce large stress, the elastic modulus of the joint should be greater than 1000 MPa.

Recurrent low back pain after spinal surgeries, such as lumbar laminectomy, is a major complication of excessive epidural fibrosis. Although multiple preclinical and clinical methods have been aimed at ameliorating epidural fibrosis, their safety and efficacy remain largely unclear. Single implanted electrospun fibrous membranes provide physical barriers that can decrease tissue fibrosis after surgery; however, they also trigger local inflammation due to the implantation of a foreign body, thus subsequently attenuating their anti-fibrosis properties. Here, we designed a strategy that permits easy incorporation of mefloquine into polylactic acid membranes, and stable long-term mefloquine release, to potentially improve anti-fibrosis effects and relieve or prevent low back pain.The electrospun fibrous membranes grafted with mefloquine showed a well-controlled early temporary peak release, and secondary drug release occurred smoothly over several weeks. Histopathological and histomorphometric results indicated that the drug-loaded membranes had excellent anti-fibrosis effects after laminectomy in rats. Inflammation and neovascularization at the surgical site indicated that the mefloquine-grafted electrospun fibrous membranes provided sustained anti-inflammatory outcomes while effectively alleviating associated neuropathic pain hypersensitivity. In summary, our study indicated that polylactic acid-mefloquine grafted electrospun fibrous membranes may be a potential local agent to mitigate epidural fibrosis and support sensory neurological function after laminectomy, thereby potentially improving patients’ postoperative outcomes.

Abstract Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows that sensory nerve orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical sensory denervation of IVD results in loss of IVD water preserve molecule chondroitin sulfate (CS), the reduction of CS bio‐synthesis gene chondroitin sulfate synthase 1 (CHSY1) expression, and dysregulated ECM homeostasis of IVD. Particularly, knockdown of sensory neuros calcitonin gene‐related peptide (CGRP) expression induces similar ECM metabolic disorder compared to sensory nerve denervation model, and this effect is abolished in CHSY1 knockout mice. Furthermore, in vitro evidence shows that CGRP regulates nucleus pulposus cell CHSY1 expression and CS synthesis via CGRP receptor component receptor activity‐modifying protein 1 (RAMP1) and cyclic AMP response element‐binding protein (CREB) signaling. Therapeutically, local injection of forskolin significantly attenuates IVD degeneration progression in mouse annulus fibrosus puncture model. Overall, these results indicate that sensory nerve maintains IVD ECM homeostasis via CGRP/CHSY1 axis and promotes IVD repair, and this expands the understanding concerning how IVD links to sensory nerve system, thus shedding light on future development of novel therapeutical strategy to IVD degeneration.

Background: Recent studies have shown that alpha-1,3-mannosyltransferase (ALG3) promoted tumorigenesis and progression in multiple cancer types. Our study planned to explore the clinical implication and potential function of ALG3 in hepatocellular carcinoma.Materials and Methods: Data from public databases were used to analyze the ALG3 expression and its impact on the clinical significance of patients with HCC. The ALG3 expression was confirmed by qRT-PCR and Western blot. Immunohistochemistry was used to confirm the ALG3 expression and explore its clinical implication in HCC. KEGG, GO, and GSEA enrichment analyses were utilized to explore the biological pathways related to ALG3 in HCC. TIMER2.0 was applied to assess the association between ALG3 and immune infiltration. CCK8, MTT, and transwell assays were used to investigate the role of ALG3 downregulation in HCC cell lines.Results: qRT-PCR, WB, and IHC proved ALG3 was highly overexpressed in HCC tissues. The Kaplan–Meier analysis verified the overexpression of ALG3 was related to poor overall survival (p < 0.001). Multivariate cox regression analysis showed that the high ALG3 expression was an independent risk prognostic factor. GSEA and TIMER2.0 predicted that ALG3 participates in cell differentiation and cycle and correlates with immune cell infiltration. Transwell assay results showed that ALG3 silencing also impaired the invasion ability of HCC cells.Conclusion: ALG3 was overexpressed and considered a potential indicator of survival in HCC, and our findings provided a novel therapeutic target for HCC.

Due to the shortage of local materials, porous basalt was used as the coarse aggregate in the prefabrication of sleepers for the Mombasa-Nairobi Railway in Kenya. To study their fatigue characteristics, the sleepers were measured under fatigue loading for their local strain, overall deformation and crack initiation. The methods used include the traditional strain measurement, the sleeper deflection measurement and the 3D optical strain measurement. To be more specific, the traditional strain measurement method was employed to compare the strain-load relation of the sleepers under different cyclic loading times. Deflection variations of the sleepers were taken into consideration to analyze sleeper local defects and the variation law of the constitutive relation for concrete. And the 3D optical non-contact strain measurement method was adopted to monitor the sleeper crack initiation and growth process under fatigue loading and analyze the crack growth law.

Hyperspectral images (HSIs) include hundreds of spectral bands, which lead to Hughes phenomenon in classification task and decrease the classification accuracy. Feature selection can remove redundant and noisy features in the HSIs to overcome this phenomenon. In real applications, we may face a HSI scene with only a few labeled samples. Meanwhile, there are adequate labeled samples in a similar HSI scene. For example, they share the same land-cover classes. The shared information can be used to help the scene with a few labeled samples in feature selection. Traditional single-scene-based feature selection appears powerless in solving such problems. Cross-scene feature selection provides an attractive way to select feature subsets by simultaneously using the information from two HSI scenes. However, spectral distribution may change due to atmospheric conditions, yielding spectral shift. In order to tackle this problem, we propose a cross-domain algorithm based on hybrid whale optimization algorithm with simulated annealing (WOASA). The newly proposed algorithm is dubbed cross-domain WOASA (CDWOASA). CDWOASA simultaneously considers the separability of different land-cover classes and the consistency of selected features between two scenes, leading to discriminative and domain-invariant characters of selected feature subset. Moreover, since the original WOASA is not able to precisely control the dimension of selected features, we propose an improvement using a sorting strategy based on the fitness function value, thus making the output feature dimension precisely controlled. The experimental results on two cross-scene HSI datasets demonstrate the superiority of CDWOASA in cross-scene feature selection.

In this paper, the probabilistic model of the controllable distributed generation in active distribution network is developed and applied to the daily stochastic optimal dispatch. The probabilistic characteristics of photovoltaic power generation system with active control capability are explored, and the relationship between the reference value of active power and its cumulative distribution function and mean value is obtained. The active power probability model of wind power generation system is improved according to the actual wind speed power curve. By fully utilizing the inverter capacity and coordinating active power, the reactive power of distributed generation is actively controlled under the constraint of power factor. Then considering the chance constraints, a daily optimal scheduling model for active distribution network with the goal of minimizing the operating cost of distribution network is developed, and the constraints that can calculate the charge and discharge times of the energy storage system are designed. The chance constrained programming is solved by the heuristic method, and the deterministic optimization steps are solved by the second-order cone programming method, respectively. The probabilistic power flow method based on stochastic response surface method is utilized to test chance constraints. Finally, the modified IEEE33 node distribution system example shows that the obtained models and algorithms are correct and can meet the requirements of safe and economic operation.

Capecitabine (CAP) is now widely used in the comprehensive treatment of digestive system tumors. Some clinical observations have shown that CAP may have immunosuppressive effects, but there is still a lack of clear experimental verification. In this study, different doses of CAP were administered to normal mice by gavage. Our results confirmed that CAP did not cause myelosuppression in bone marrow tissue; CAP selectively reduced the proportion of T cells and the concentration of related pro-inflammatory cytokines, while it increased the concentration of anti-inflammatory cytokines. Thymidylate phosphorylase (TP) is the key enzyme for the transformation of CAP in vivo; this study confirmed that T cells express TP, but the bone marrow tissue lacks TP expression, which explains the selectivity in pharmacodynamic effects of CAP. In addition, it was confirmed that CAP can induce T cell apoptosis in vivo and in vitro. In vitro experiments showed that CAP-induced T cell apoptosis was related to TP expression, endoplasmic reticulum stress (ERS) induction, reactive oxygen species (ROS) production, and mitochondria-mediated apoptosis activation. Therefore, this study confirmed that the differential expression of TP in cells and tissues explains why CAP avoids the toxic effects of myelosuppression while inducing T cell apoptosis to exert the immunosuppressive effect. Therefore, CAP may become an immunosuppressive agent with a simultaneous anti-cancer effect, which is worthy of further studies.

Abstract Background Prostate cancer (PCa) is the second leading cause of mortality and a leading cause of malignant tumors in males. Prostate cancer stem cells (PCSCs) are likely the responsible cell types for cancer initiation, clinical treatment failure, tumor relapse, and metastasis. Estrogen receptor alpha (ERα) is mainly expressed in the basal layer cells of the normal prostate gland and has key roles in coordinating stem cells to control prostate organ development. Here, we investigated the roles of the estrogen-ERα signaling pathway in regulating PCSCs. Methods Correlation of CD49f and ERα/NOTCH1 was analyzed in human clinical datasets and tissue samples. Flow cytometry was used to sort CD49fHi and CD49fLow cells. EZH2 recruitment by ERα and facilitation of ERα binding to the NOTCH1 promoter was validated by Co-IP and ChIP. Primary tumor growth, tumor metastasis and sensitivity to 17β-estradiol (E2) inhibitor (tamoxifen) were evaluated in castrated mice. Results ERα expression was significantly higher in CD49fHi prostate cancer basal stem-like cells (PCBSLCs), which showed basal and EMT features with susceptibility to E2 treatment. ERα-induced estrogen effects were suggested to drive the NOTCH1 signaling pathway activity via binding to the NOTCH1 promoter. Moreover, EZH2 was recruited by ERα and acted as a cofactor to assist ERα-induced estrogen effects in regulating NOTCH1 in PCa. In vivo, E2 promoted tumor formation and metastasis, which were inhibited by tamoxifen. Conclusions Our results implicated CD49f+/ERα + prostate cancer cells associated with basal stem-like and EMT features, named EMT-PCBSLCs, in heightened potential for promoting metastasis. NOTCH1 was regulated by E2 in CD49fHi EMT-PCBSLCs. These results contribute to insights into the metastatic mechanisms of EMT-PCBSLCs in PCa.

Wheel hollow wear of high-speed train is one of the main damage types for the wheel. By optimizing the vehicle and track parameters and matching the wheel-rail profile, the hollow wear of wheel can be reduced. In order to study the sensitivity of vehicle and track parameters to the wheel hollow wear, the sensitivity of suspension parameters and the track parameters of the CRH2Ctype high-speed train wheel on the hollow wear of the wheel was studied by the parameter sensitivity analysis method. The concept of the cumulative wear power dissipation was put forward. The distribution characteristics of the wheel hollow wear under the different wheel/rail treads matching were forecasted. The results show that the damping of antihunting motion damper of the vehicle is the most sensitive to the maximum cumulative wear power dissipation of the wheel, followed by the longitudinal stiffness of tumbler journal box node, lateral stiffness of air-spring suspension, vertical damping of primary suspension, vertical stiffness of track, and vertical damping of track. According to the analysis from the combination of sensitive parameters, the cumulative wear power dissipation is unevenly distributed in the lateral direction of the wheel tread and has the obvious peak area, which is basically the same as the actual wear distribution location in the field. The matching of the LMA wheel tread and the CN60N rail tread is a good choice to slow down the hollow wear and reduce the wheel wear rate. And the wheel reprofiling should be timely carried out, otherwise the wear rate would increase and the hollow wear would become more serious.

A reaction-based two-photon (TP) ratiometric fluorescence probe Z2 has been developed and successfully applied to detect and image fluoride ion in living cells and tissues. The Z2 probe was designed designed to utilize an ICT mechanism between n-butylnaphthalimide as a fluorophore and tert-butyldiphenylsilane (TBDPS) as a response group. Upon addition of fluoride ion, the Si-O bond in the Z2 would be cleaved, and then a stronger electron-donating group was released. The fluorescent changes at 450 and 540 nm, respectively, made it possible to achieve ratiometric fluorescence detection. The results indicated that the Z2 could ratiometrically detect and image fluoride ion in living cells and tissues in a depth of 250 μm by two-photon microscopy (TPM).

The wheelset maintenance cost is an important part of train maintenance cost. Researchers and railway operators have been closely concerned about the way to minimize residual stress at wheel tread and surface roughness during wheel reprofiling, thereby reducing the wheel damage during operation, extending the wheelset service life, and cutting down wheelset maintenance cost. The present study involves dynamic simulation of tread reprofiling process by building a finite element model of wheel reprofiling, taking the wheel steel as research object. This paper makes a comprehensive analysis of surface roughness and residual stress distribution of wheel tread under different milling parameters. The simulation results indicate that the increase in cutting speed and back cutting depth causes the chip morphology to change while impairing the machined surface quality. Once serrated chip occurs, it means wheel tread machining quality deteriorates remarkably. In this way, the paper associates macroscopic chip morphology with microcosmic surface roughness and internal residual stress to provide theoretical basis for optimization of wheel reprofiling process.

There is confusion in the original design concept for the tensioning of longitudinally connected reinforcement of the CRTSII (China Railway Track System) slab ballastless track. In order to clarify the effect of tension value of longitudinal reinforcement on the mechanical characteristics of the ballastless track, a three-dimensional finite element model, considering the nonlinear interaction between the track slab and cement-emulsified asphalt (CA) mortar of the CRTSII slab ballastless track, was established. The mechanical characteristics of the track structure under longitudinal tension load and temperature gradient load of the longitudinal joint were calculated. A method of applying prestress to post-pouring concrete was proposed according to the concept of prestress loss of pretensioning prestressed concrete, a reasonable tensile force value was proposed after the crack width, and the reinforcement stress of the ballastless track in the operation stage was checked and calculated according to the concrete design principle. When the tension force is greater than 300 kN, it is harmful to the bonding between the slab and mortar layer, which is prone to interlayer damage. In order to add prestress to concrete with wide joints to ensure the longitudinal stability of the ballastless track, and that the reinforcement stress and crack width meet design requirements, it is suggested that the tension force value should be 230 kN. Further, the temperature difference between reinforcement and concrete should be 30 °C before the initial curdle of wide joint concrete.

The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3'-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.