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In order to investigate the dynamic response and rock mass damage characteristics of cavities with different shapes under blasting loads, this paper, through a combination of model tests and numerical simulations, studies the stress distribution, strain, failure modes, and blasting fragment size distribution of cavities with different shapes subjected to blasting loads. The results show that under the action of blasting loads, the presence of cavities with different shapes significantly affects the blasting effects and rock mass damage. Spherical cavities exhibit excellent blast resistance, whereas rectangular and triangular cavities are prone to stress concentration at their tips, which in turn promotes rock mass damage and failure. Subsequent analysis of the blasting fragment sizes reveals that rectangular and triangular cavities yield more favorable blasting results than spherical cavities. The research findings provide important theoretical foundations and practical guidance for the design and construction of underground engineering blasting, contributing to enhancing engineering safety and promoting the sustainable development of the underground engineering industry. [ABSTRACT FROM AUTHOR]

This paper expounds the suggestions and thoughts on the construction of “One Syndrome and One Product” Chinese medicine nursing brand from four aspects: the hierarchical management mode of nursing system, the training of multi-disciplinary nursing professionals, the integration of Traditional Chinese Medicine nursing and rehabilitation, and the humanistic care of Traditional Chinese Medicine nursing, so as to optimize the nursing scheme of traditional Chinese medicine and create the nursing service brand of Traditional Chinese Medicine with different characteristics, And make nurses have evidence to rely on in nursing work, improve the patient's treatment experience. (本文从护理体系分级管理模式、多学科护理专业人才培养、中医医护康复一体化、中医护理人文关怀4个方面阐述了对“一证一品”中医护理品牌建设的建议与思考, 以期为优化中医护理方案, 创立各具特色的中医护理服务品牌, 提高患者的就诊体验提供参考。)

Background: Previous studies reported that various miRNAs participate in autoimmune diseases, but the potential regulatory mechanism of miRNAs in autoimmune thyroiditis (AIT) needs further exploration. Objective: This study aimed to further verify that miR-326 contributes to AIT by regulating Th17/Treg balance through Ets-1 using lentiviral gene delivery through tail vein and thyroid injection in NOD.H-2h4 mice. Materials and Methods: Five-week-old NOD.H-2h4 mice were divided randomly into tail vein and thyroid injection groups, and each received either mmu-miR-326 sponge (LV-sponge) or lentiviral vector control. Mice were divided for tail vein injection: the therapeutic LV-ctrl, therapeutic LV-sponge, prophylactic LV-ctrl, and prophylactic LV-sponge groups. The control group was fed high-iodine water without vein injection. The thyroid infiltration of lymphocytes and serum TgAb value were investigated by thyroid hematoxylin and eosin (HE) staining and ELISA, respectively. Ets-1 and lymphocyte counts were measured by RT-PCR, western blotting, and flow cytometry. The thyroid CD4+IL-17a+ cells and CD4+Ets-1+ cells were detected by immunofluorescence, and the serum cytokines were tested by ELISA. Results: In the tail vein injection groups, the thyroid inflammatory score and serum TgAb titer were significantly lower in the LV-sponge groups than in the control and LV-ctrl groups while Ets-1 protein expression in mouse spleens was increased in the LV-sponge groups. Moreover, Th17/Treg ratio declined in the LV-sponge group and decreased significantly in the prophylactic LV-sponge group (P = 0.036) tested by flow cytometry. Immunofluorescence showed that, in LV-sponge groups, CD4+IL-17a+ cells were decreased significantly (P = 0.001), while CD4+Ets-1+ cells were increased significantly in the LV-sponge group (P = 0.029). The serum IL-17/IL-10 was decreased significantly in the LV-sponge group (P < 0.05). In the thyroid injection groups, the thyroid inflammatory score and serum TgAb titer in the LV-sponge group decreased significantly compared with those in the LV-ctrl group (P < 0.05). In addition, in LV-sponge groups, CD4+IL-17a+ cells were decreased, while CD4+Ets-1+ cells were increased significantly in the inhibition group evaluated by immunofluorescence. Moreover, tail vein injection of LV-sponge resulted in much lower TgAb levels in thyroiditis compared with thyroid injection. Conclusion: MiR-326 targeted therapy may be a promising approach for AIT. In addition, tail vein injection may achieve a better intervention effect than thyroid injection. [ABSTRACT FROM AUTHOR]

Exosomes are extracellular vesicles that can participate in autoimmune diseases. The purpose of this study was to explore whether circulating exosomes are involved in Graves' disease (GD) pathogenesis. In this study, serum exosomes were extracted from 26 healthy controls (HC-EXO), 26 GD patients (GD-EXO), and 7 Graves' ophthalmopathy patients (GO-EXO). For each group, the total protein content was detected, and thyrotropin receptor, insulin-like growth factor 1 receptor (IGF-1R), heat shock protein 60 (HSP60), and cluster of differentiation (CD) 63 expression were analyzed by Western blotting (WB). Healthy volunteer-derived peripheral blood mononuclear cells (PBMCs) and HC-EXO or GD-EXO were cocultured for 24 h, and immunofluorescence was used to observe the locations of the exosomes and toll-like receptor (TLR) 2/3. CD11c+TLR2+ and CD11c+TLR3+ cell percentages were determined by flow cytometry. Myeloid differentiation factor 88 (MyD88), toll/interleukin (IL)-1 receptor domain-containing adaptor inducing interferon-β (TRIF) and p-P65 expression were analyzed by WB. IL-6 and IL-1β supernatant levels were detected using enzyme-linked immunosorbent assay. The results showed that the total protein concentration was similar among GD-EXO, GO-EXO, and HC-EXO. IGF-1R and HSP60 expression was significantly higher in GD-EXO and GO-EXO than in HC-EXO. After coculturing PBMCs with GD-EXO or HC-EXO for 24 h, GD-EXO could bind to TLR2/3. GD-EXO significantly increased CD11c+TLR2+ and CD11c+TLR3+ cell percentages; MyD88, TRIF, and p-P65 protein expression; and IL-6 and IL-1β levels. In conclusion, we first demonstrated that GD-EXO and GO-EXO highly expressed IGF-1R and HSP60. GD-EXO may induce an inflammatory response through the TLR/NF-κB signaling pathway and be involved in the pathogenesis of GD. [ABSTRACT FROM AUTHOR]

The etiology of schizophrenia (SCZ) is regarded as one of the most fundamental puzzles in current medical research, and its diagnosis is limited by the lack of objective molecular criteria. Although plenty of studies were conducted, SCZ gene signatures identified by these independent studies are found highly inconsistent. As one of the most important factors contributing to this inconsistency, the feature selection methods used currently do not fully consider the reproducibility among the signatures discovered from different datasets. Therefore, it is crucial to develop new bioinformatics tools of novel strategy for ensuring a stable discovery of gene signature for SCZ. In this study, a novel feature selection strategy (1) integrating repeated random sampling with consensus scoring and (2) evaluating the consistency of gene rank among different datasets was constructed. By systematically assessing the identified SCZ signature comprising 135 differentially expressed genes, this newly constructed strategy demonstrated significantly enhanced stability and better differentiating ability compared with the feature selection methods popular in current SCZ research. Based on a first-ever assessment on methods' reproducibility cross-validated by independent datasets from three representative studies, the new strategy stood out among the popular methods by showing superior stability and differentiating ability. Finally, 2 novel and 17 previously reported transcription factors were identified and showed great potential in revealing the etiology of SCZ. In sum, the SCZ signature identified in this study would provide valuable clues for discovering diagnostic molecules and potential targets for SCZ. [ABSTRACT FROM AUTHOR]

Label-free quantification (LFQ) with a specific and sequentially integrated workflow of acquisition technique, quantification tool and processing method has emerged as the popular technique employed in metaproteomic research to provide a comprehensive landscape of the adaptive response of microbes to external stimuli and their interactions with other organisms or host cells. The performance of a specific LFQ workflow is highly dependent on the studied data. Hence, it is essential to discover the most appropriate one for a specific data set. However, it is challenging to perform such discovery due to the large number of possible workflows and the multifaceted nature of the evaluation criteria. Herein, a web server ANPELA (https://idrblab.org/anpela/) was developed and validated as the first tool enabling performance assessment of whole LFQ workflow (collective assessment by five well-established criteria with distinct underlying theories), and it enabled the identification of the optimal LFQ workflow(s) by a comprehensive performance ranking. ANPELA not only automatically detects the diverse formats of data generated by all quantification tools but also provides the most complete set of processing methods among the available web servers and stand-alone tools. Systematic validation using metaproteomic benchmarks revealed ANPELA's capabilities in 1 discovering well-performing workflow(s), (2) enabling assessment from multiple perspectives and (3) validating LFQ accuracy using spiked proteins. ANPELA has a unique ability to evaluate the performance of whole LFQ workflow and enables the discovery of the optimal LFQs by the comprehensive performance ranking of all 560 workflows. Therefore, it has great potential for applications in metaproteomic and other studies requiring LFQ techniques, as many features are shared among proteomic studies. [ABSTRACT FROM AUTHOR]

Th17 and regulatory lymphocyte subsets such as Tregs and Bregs have been reported to play important roles in autoimmune diseases. The aim of this work was to perform quantitative studies of circulating Th17, Tregs, and Bregs in patients with new-onset Graves’ disease (GD). Twenty GD patients and 20 healthy controls were involved in this study. Blood samples were taken for flow cytometry detection of CD4+IL-17+ Th17, CD4+Foxp3+ Tregs, and CD19+CD1dhiCD5+ Bregs and meanwhile, for real-time PCR measurement of gene expressions of RORγt, IL-17 and IL-10. The proportions of Tregs and Bregs as well as the Foxp3 gene expression but not IL-10 were significantly decreased in GD group compared with the healthy controls. The frequency of Th17 together with the gene expressions of RORγt and IL-17 were significantly increased in the GD group. Furthermore, the Th17/Treg ratio was also significantly higher in GD group. A significant positive correlation between Th17 and TSAb (r=0.656, p<0.001) but significant negative correlations between Treg/Breg and TSAb (r=-0.339, p=0.032; r=-0.759, p<0.001) were identified among the participants. This study indicated that increased Th17 and impaired Treg responses, along with a decreased number of CD19+CD1dhiCD5+ Breg cells, were involved in GD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported that various miRNAs participate in autoimmune diseases, but the potential regulatory mechanism of miRNAs in autoimmune thyroiditis (AIT) needs further exploration., Objective: This study aimed to further verify that miR-326 contributes to AIT by regulating Th17/Treg balance through Ets-1 using lentiviral gene delivery through tail vein and thyroid injection in NOD.H-2 h4 mice., Materials and Methods: Five-week-old NOD.H-2 h4 mice were divided randomly into tail vein and thyroid injection groups, and each received either mmu-miR-326 sponge (LV-sponge) or lentiviral vector control. Mice were divided for tail vein injection: the therapeutic LV-ctrl, therapeutic LV-sponge, prophylactic LV-ctrl, and prophylactic LV-sponge groups. The control group was fed high-iodine water without vein injection. The thyroid infiltration of lymphocytes and serum TgAb value were investigated by thyroid hematoxylin and eosin (HE) staining and ELISA, respectively. Ets-1 and lymphocyte counts were measured by RT-PCR, western blotting, and flow cytometry. The thyroid CD4 + IL-17a + cells and CD4 + Ets-1 + cells were detected by immunofluorescence, and the serum cytokines were tested by ELISA., Results: In the tail vein injection groups, the thyroid inflammatory score and serum TgAb titer were significantly lower in the LV-sponge groups than in the control and LV-ctrl groups while Ets-1 protein expression in mouse spleens was increased in the LV-sponge groups. Moreover, Th17/Treg ratio declined in the LV-sponge group and decreased significantly in the prophylactic LV-sponge group ( P = 0.036) tested by flow cytometry. Immunofluorescence showed that, in LV-sponge groups, CD4 + IL-17a + cells were decreased significantly ( P = 0.001), while CD4 + Ets-1 + cells were increased significantly in the LV-sponge group ( P = 0.029). The serum IL-17/IL-10 was decreased significantly in the LV-sponge group ( P < 0.05). In the thyroid injection groups, the thyroid inflammatory score and serum TgAb titer in the LV-sponge group decreased significantly compared with those in the LV-ctrl group ( P < 0.05). In addition, in LV-sponge groups, CD4 + IL-17a + cells were decreased, while CD4 + Ets-1 + cells were increased significantly in the inhibition group evaluated by immunofluorescence. Moreover, tail vein injection of LV-sponge resulted in much lower TgAb levels in thyroiditis compared with thyroid injection., Conclusion: MiR-326 targeted therapy may be a promising approach for AIT. In addition, tail vein injection may achieve a better intervention effect than thyroid injection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Wang, Cui, Wang, Fan, Li, Shan and Teng.)

Exosomes have been intensively studied in autoimmune diseases, and circulating exosomes and microvesicles have also been explored in autoimmune thyroiditis (AITD). However, the role of thyroid cell-derived exosomes in immune responses is unclear. We showed that IFN-γ-treated Nthy-ori 3-1 cell-derived exosomes (IFN-γ-Exo) harbored TPO, HSP60 and MHC-II and activated dendritic cells (DCs) in vitro. Compared with Exo-targeted DCs (DC Exo ), IFN-γ-Exo-targeted DCs (DC IFN-γ-Exo ) promoted the expression and release of proinflammatory cytokines, such as IFN-γ, IL-17A and IL-22, from CD4 + T lymphocytes and inhibited the expression and release of anti-inflammatory cytokines, such as IL-4, IL-10 and TGF-β1; however, IFN-γ-Exo did not have this effect compared with Nthy-ori 3-1 cell-derived exosomes (Exo). DC IFN-γ-Exo stimulates the expression and release of cytokines from CD4 + T lymphocytes more efficiently than IFN-γ-Exo. Thus, DC IFN-γ-Exo may effectively induce CD4 + T lymphocyte-mediated immune responses and play a role in the occurrence and development of AITD., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The degree of Zn 2+ and Ta 5+ ions ordering could play an important role in the dielectric loss in Ba(Zn 1/3 Ta 2/3 )O₃ (BZT) ceramics. However, the influence of the grain size of Ba(B' 1/3 B″ 2/3 )O₃ ceramics with nano or sub-micron grains on the ordering domains structure is still not clear. In the present paper, highly dense (~98%) BZT microwave dielectric ceramics with homogeneous sub-micron structure (~330 nm) were prepared through spark plasma sintering (SPS). High resolution transmission electron microscopy combined with X-ray diffraction (XRD)clearly showed that the B-site ordering structure of sintered BZT samples by SPS becomes the B-site long-range 1:2 ordering as annealing proceeds. In contrast, the short-range 1:2 ordering in non-annealed counterparts was also present, which was not detectable by XRD. The size of B-site ordering domains enlarged with annealing temperature. The sub-micron structure of sintered BZT ceramics by SPS remained stable at up to 1400 C; however, the size of B-site 1:2 ordering domain was more than five times larger, which led to a significant increase of the quality factor ( Q·f ) to 37,700 GHz from 15,000 GHz.

Th17 and regulatory lymphocyte subsets such as Tregs and Bregs have been reported to play important roles in autoimmune diseases. The aim of this work was to perform quantitative studies of circulating Th17, Tregs, and Bregs in patients with new-onset Graves' disease (GD). Twenty GD patients and 20 healthy controls were involved in this study. Blood samples were taken for flow cytometry detection of CD4 + IL-17 + Th17, CD4 + Foxp3 + Tregs, and CD19 + CD1d hi CD5 + Bregs and meanwhile, for real-time PCR measurement of gene expressions of ROR γ t, IL-17 and IL-10. The proportions of Tregs and Bregs as well as the Foxp3 gene expression but not IL-10 were significantly decreased in GD group compared with the healthy controls. The frequency of Th17 together with the gene expressions of ROR γ t and IL-17 were significantly increased in the GD group. Furthermore, the Th17/Treg ratio was also significantly higher in GD group. A significant positive correlation between Th17 and TSAb ( r = 0.656, p < 0.001) but significant negative correlations between Treg/Breg and TSAb ( r = -0.339, p = 0.032; r = -0.759, p < 0.001) were identified among the participants. This study indicated that increased Th17 and impaired Treg responses, along with a decreased number of CD19 + CD1d hi CD5 + Breg cells, were involved in GD pathogenesis.