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Abstract Electromagnetic fields (EMFs) have emerged as an effective treatment for osteoporosis. However, the specific mechanism underlying their therapeutic efficacy remains controversial. Herein, we confirm the pro-osteogenic effects of 15 Hz and 0.4-1 mT low-frequency sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs). Subsequent miRNA sequencing reveal that miR-34b-5p is downregulated in both the 0.4 mT and 1 mT SEMFs-stimulated groups. To clarify the role of miR-34b-5p in osteogenesis, BMSCs are transfected separately with miR-34b-5p mimic and inhibitor. The results indicate that miR-34b-5p mimic transfection suppress osteogenic differentiation, whereas inhibition of miR-34b-5p promote osteogenic differentiation of BMSCs. In vivo assessments using microcomputed tomography, H&E staining, and Masson staining show that miR-34b-5p inhibitor injections alleviate bone mass loss and trabecular microstructure deterioration in ovariectomy (OVX) rats. Further validation demonstrates that miR-34b-5p exerts its effects by regulating STAC2 expression. Modulating the miR-34b-5p/STAC2 axis attenuate the pro-osteogenic effects of low-frequency SEMFs on BMSCs. These studies indicate that the pro-osteogenic effect of SEMFs is partly due to the regulation of the miR-34b-5p/STAC2 pathway, which provides a potential therapeutic candidate for osteoporosis.

This work proposes a novel unsupervised deep non-negative matrix factorization (NMF) model called AGDNMF by deep exploration of the structure of the original data. Compared with the existing NMF research results, the model explores the deep association of data and constructs accurate spatial structure from a new perspective. Specifically, for the purpose of effectively learning low-dimensional representations of data. This work constructs a deep NMF method to approximate the coding structure of the original data, which enables AGDNMF to learn the hierarchical mapping relationship between the categories of the original data, and learn the hidden association information of the data from low-to-high in the middle layer. Moreover, the model gives an adversarial graph regularization representation for the manifoldization of data structures to push away the spatial distances between different sample clusters. Finally, based on the mathematical model of the proposed algorithm, the optimization strategy and convergence proof are given. Extensive experiments and data analysis demonstrate that the proposed model outperforms state-of-the-art unsupervised NMF methods.

The prediction of mechanical properties of hot rolled strips can be used for on-line dynamic control of product properties and optimal design of new steel grade. Tensile strength is an important index of the mechanical properties for hot rolled strips. The influencing factors of tensile strength include alloy elements, microstructure, and production process parameters. It is very crucial to establish a reliable prediction model of steel tensile strength based on these factors to improve the mechanical properties. This paper proposes a prediction model which combines a generalized radial basis function neural network and composite expectile regression to solve nonlinear problems and data heterogeneity problems in modeling. At the same time, CS algorithm (Cuckoo Search) was applied to develop an estimation procedure, which overcomes the shortcoming of traditional gradient descent algorithm by avoiding to fall into local optimum. Because expectile regression can describe the conditional distribution, and neural network has strong non-linear interpretation ability, the proposed model enables us to explore potential nonlinear relationships among variables. Based on the measured data collected from a hot rolling production process, the experimental results show that the model proposed in this paper has better prediction accuracy, the mean absolute percentage error (MAPE) and root mean square error (RMSE) are 2.49

Abstract Background The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future. Methods In this research, bone marrow mesenchymal stem cells (BMSCs) seeded on 3D-printed scaffolds were treated with sinusoidal EMFs in vitro. Then, 5.5 mm critical-sized calvarial defects were created in rats, and the cell scaffolds were implanted into the defects. In addition, the molecular and cellular mechanisms by which EMFs regulate BMSCs were explored with various approaches to gain deeper insight into the effects of EMFs. Results The cell scaffolds treated with EMF successfully accelerated the repair of critical-sized calvarial defects. Further studies revealed that EMF could not directly induce the differentiation of BMSCs but improved the sensitivity of BMSCs to BMP signals by upregulating the quantity of specific BMP (bone morphogenetic protein) receptors. Once these receptors receive BMP signals from the surrounding milieu, a cascade of reactions is initiated to promote osteogenic differentiation via the BMP/Smad signalling pathway. Moreover, the cytokines secreted by BMSCs treated with EMF can better facilitate angiogenesis and osteoimmunomodulation which play fundamental roles in bone regeneration. Conclusion In summary, EMF can promote the osteogenic potential of BMSCs and enhance the paracrine function of BMSCs to facilitate bone regeneration. These findings highlight the profound impact of EMF on tissue engineering and provide a new strategy for the clinical treatment of bone defects.

Abstract Background Intervertebral fusion is the most common surgery to treat lumbar degenerative disease (LDD). And the graft material used in the operation is derived from the iliac crest to promote fusion. However, autografts possess the fatal disadvantage of lack of source. Therefore, economical and practical bone substitutes are urgently needed to be developed. Sinusoidal electromagnetic fields (EMF) combined with tissue engineering techniques may be an appropriate way to promote intervertebral fusion. Methods In this research, porous scaffolds made of polycaprolactone (PCL) and nano-hydroxyapatite (nHA) were used as cell carriers. Then, the scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were treated with sinusoidal electromagnetic field and the osteogenic capability of BMSCs was tested later. In addition, an intervertebral disc of the tail vertebra of the rat was removed to construct a spinal intervertebral fusion model with a cell-scaffold implanted. The intervertebral fusion was observed and analyzed by X-ray, micro-CT, and histological methods. Results BMSCs stimulated by EMF possess splendid osteogenic capability under an osteogenic medium (OM) in vitro. And the conditioned medium of BMSCs treated with EMF can further promote osteogenic differentiation of the primitive BMSCs. Mechanistically, EMF regulates BMSCs via BMP/Smad and mitogen-activated protein kinase (MAPK)-associated p38 signaling pathways. In vivo experiments revealed that the scaffold loaded with BMSCs stimulated by EMF accelerated intervertebral fusion successfully. Conclusion In summary, EMF accelerated intervertebral fusion by improving the osteogenic capacity of BMSCs seeded on scaffolds and might boost the paracrine function of BMSCs to promote osteogenic differentiation of the homing BMSCs at the injured site. EMF combined with tissue engineering techniques may become a new clinical treatment for LDD.

Despite impressive progress, a significant portion of patients still experience primary or secondary resistance to chimeric antigen receptor (CAR) T-cell immunotherapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The mechanism of primary resistance involves T-cell extrinsic and intrinsic dysfunction. In the present study, a total of 135 patients of DLBCL treated with murine CD19/CD22 cocktail CAR T-therapy were assessed retrospectively. Based on four criteria (maximal expansion of the transgene/CAR-positive T-cell levels post-infusion [Cmax], initial persistence of the transgene by the CAR transgene level at +3 months [Tlast], CD19+ B-cell levels [B-cell recovery], and the initial response to CAR T-cell therapy), 48 patients were included in the research and divided into two groups (a T-normal group [n=22] and a T-defect [n=26] group). According to univariate and multivariate regression analyses, higher lactate dehydrogenase (LDH) levels before leukapheresis (hazard ratio (HR) = 1.922; p = 0.045) and lower cytokine release syndrome (CRS) grade after CAR T-cell infusion (HR = 0.150; p = 0.026) were independent risk factors of T-cell dysfunction. Moreover, using whole-exon sequencing, we found that germline variants in 47 genes were significantly enriched in the T-defect group compared to the T-normal group (96% vs. 41%; p

Abstract Background Current strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough. Methods In this study, polylactic acid/hydroxyapatite (PLA/HA) composite scaffold was fabricated. After seeding rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds, the effects of electromagnetic fields (EMF) on the proliferation and osteogenic differentiation capacity of BMSCs were investigated. Additionally, 6-mm critical-sized calvarial defect was created in rats. BMSC-laden scaffolds were implanted into the defects with or without EMF treatment. Results Our results showed that PLA/HA composite scaffolds exhibited uniform porous structure, high porosity (~ 70%), suitable compression strength (31.18 ± 4.86 MPa), modulus of elasticity (10.12 ± 1.24 GPa), and excellent cyto-compatibility. The proliferation and osteogenic differentiation capacity of BMSCs cultured on the scaffolds were enhanced with EMF treatment. Mechanistically, EMF exposure functioned partly by activating mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways. In vivo, significantly higher new bone formation and vascularization were observed in groups involving scaffold, BMSCs, and EMF treatment, compared to scaffold alone. Furthermore, after 12 weeks of implanting, craniums in groups including scaffold, BMSCs, and EMF exposure showed the greatest biomechanical properties. Conclusion In conclusion, EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration.

The most common method used to document monetary transactions in Brazil is by issuing electronic invoices (NF-e). The audit of electronic invoices is essential, and this can be improved by using data mining solutions, such as clustering and anomaly detection. However, applying these solutions is not a simple task because NF-e data contains millions of records with noisy fields and nonstandard documents, especially short text descriptions. In addition to these challenges, it is costly to extract information from short texts to identify traces of mismanagement, embezzlement, commercial fraud or tax evasion. Analyzing such data can be more effective when divided into well-defined groups. However, efficient solutions for clustering data with characteristics similar to NF-es have not yet been proposed in the literature. We developed ELINAC, a service for clustering short-text data in NF-es that uses an automatic encoder to cluster data. ELINAC aids in auditing transactions documented in NF-e, clustering similar data by short-text descriptions and making anomaly detection in numeric fields easier. For this, ELINAC explores how to model the automatic encoder without increasing the calculation costs to suppress a large number of short text data. In the worst case, the results show that ELINAC efficiently groups data while performing three times faster than solutions previously adopted in the literature.

In order to extract fault impulse feature of large-scale rotating machinery from strong background noise, a sparse feature extraction method based on sparse decomposition combined multiresolution generalized S transform is proposed in this paper. In this method, multiresolution generalized S transform is employed to find the optimal atom for every iteration, which firstly takes in to account the generalized S transform with discretized adjustment factors, then builds an atom corresponding to the maximum energy. The multiresolution generalized S transform has better accuracy compared to generalized S transform and faster searching speed compared to the orthogonal matching pursuit method in selecting the optimal atom. Then, the orthogonal matching pursuit method is used to decompose the signal into several optimal atoms. The proposed method is applied to analyze the simulated signal and vibration signals collected from experimental failure rolling bearings. The results prove that the proposed method has better performances such as high precision and fast decomposition speed than the traditional orthogonal matching pursuit method method and local mean decomposition method.

To obtain the good flatness of hot-rolled stainless-steel strips, high-precision shape control has always been the focus of research. In hot rolling, the quadratic wave (centre buckle and edge wave) can usually be controlled effectively. However, the quarter buckle of the strip is still a challenge to solve. In this paper, a prediction model of roll deflection and material flow is established to study the change rule and control technology of the quarter buckle. The effects of the process parameters on the quarter buckle are analysed quantitatively. The process parameters affect the quarter buckle and the quadratic wave simultaneously. This coupling makes the control of the quarter buckle difficult. The distribution of lateral temperature and the quartic crown of the strip have less effect on the quadratic wave but have a great effect on the quarter buckle. Finally, a new technology for work roll contour is developed to improve the quarter buckle. Through industrial application, the model and the new contour are proved to be effective.