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Background: Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired self-inflammatory disease, involving a variety of immune cells, and it is also affected by genetic and environmental susceptibility. However, the precise causative relationship between the phenotype of immune cells and JIA remains unclear to date. The objective of our study is to approach this inquiry from a genetic perspective, employing a method of genetic association analysis to ascertain the causal relationship between immune phenotypes and the onset of JIA. Methods: In this study, a two-sample Mendelian randomization (MR) analysis was used to select single nucleotide polymorphisms (SNPs) significantly associated with immune cells as instrumental variables to analyze the bidirectional causal relationship between 731 immune cells and JIA. There were four types of immune features (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)). Finally, the heterogeneity and horizontal reproducibility of the results were verified by sensitivity analysis, which ensured more robust results. Results: We found that CD3 on CM CD8br was causally associated with JIA at the level of 0.05 significant difference (95% CI = 0.630 ~ 0.847, P = 3.33 × 10−5, PFDR = 0.024). At the significance level of 0.20, two immunophenotypes were causally associated with JIA, namely: HLA DR on CD14+ CD16- monocyte (95% CI = 0.633 ~ 0.884, P = 6.83 × 10–4, PFDR = 0.16) and HLA DR on CD14+ monocyte (95% CI = 0.627 ~ 0.882, P = 6.9 × 10−4, PFDR = 0.16). Conclusion: Our study assessed the causal effect of immune cells on JIA from a genetic perspective. These findings emphasize the complex and important role of immune cells in the pathogenesis of JIA and lay a foundation for further study of the pathogenesis of JIA. [ABSTRACT FROM AUTHOR]

The bacterial microenvironment-activated nanocatalytic antibacterial strategy has attracted extensive attention owing to the high specificity to eliminate pathogens, which provides opportunities to solve antibiotic resistance. However, the relatively high pH value and insufficient endogenous H2O2 level in bacterial microenvironment limits the efficiency of Fenton reactions induced by these nanocatalytic agents, leading to unsatisfied antibacterial performance. Herein, bimetallic peroxide was first reported as a high-efficiency antibacterial nanocatalyst with high pH-activated, H2O2 self-supply and synergistic effect-enhanced cascade Fenton chemistry. An isolated spray vial was further developed to achieve in situ gelation at the wound site, adapt to irregular wound surface, and maintain long-term release of nanocatalyst. As a result, wound healing was efficiently promoted corresponding to excellent nanocatalytic antibacterial efficacy. Thus, our in situ sprayed nanocatalytic antibacterial gel provides a promising paradigm for high-efficiency bacterial infection therapy. [ABSTRACT FROM AUTHOR]

Six rare‐earth tantalate high‐entropy ceramics of (5RE.2)Ta3O9 (RE represents any five elements selected from La, Ce, Nd, Sm, Eu, Gd) were designed and prepared by spark plasma sintering process at 1400°C in this study. The (5RE.2)Ta3O9 ceramics only consist of a single‐phase solid solution with perovskite structure. Their relative densities are all above 90%, and the average grain size is in the range of 1.47–2.92 μm. The thermal conductivity of (5RE.2)Ta3O9 ceramics is in 2.24–1.90 W m−1 K−1 (25°C–500°C), which is much lower than that of yttria‐stabilized zirconia. In six samples, (La.2Nd.2Sm.2Gd.2Eu.2)Ta3O9 possesses a thermal conductivity of 1.90 W m−1 K−1, a thermal expansion coefficient of 3.47 × 10−6 K−1 (500°C), a Vickers hardness of about 7.33 GPa, and a fracture toughness of about 5.20 MPa m1/2, which are suitable for its application as thermal barrier coatings. [ABSTRACT FROM AUTHOR]

Iron tailings powder (ITP) is a kind of solid waste, which pollutes the environment, without any treatment. The application of ITP in cement concrete is a good choice. In this study, the influence of ITP on the flowability, compressive strength, chloride ion permeability and the attenuation of the performance of cement concrete during freeze–thaw cycle (F-T) damage are investigated. An X-ray diffraction, an analysis of the pores and a scanning electron microscope (SEM) are obtained to analyze the mechanism of cement concrete's performance. The results show that the addition of ITP can decrease the flowability of fresh cement concrete. Cement concrete with a 7% ITP to mass ratio of the total aggregate shows the highest compressive strength and the minimum chloride ion permeability. The relative dynamic modulus of the elasticity of the specimens with 7% ITP during the F-T is the highest. The corresponding mass loss rate is the lowest. The mercury intrusion analysis results show that the pore volume of the specimens with 7% ITP is the lowest. The SEM results confirm that the specimens with 7% ITP show the densest microstructures. [ABSTRACT FROM AUTHOR]

Liquid accelerating agents have the advantages of simple operation and fast construction, and have become indispensable admixtures in shotcrete. However, most liquid accelerating agents in the market at present contain alkali or fluorine, which adversely affect concrete and seriously threaten the physical and mental health of workers. Therefore, in view of the above deficiencies, it is necessary to develop a new type of alkali-free fluorine-free liquid accelerating agent. In this paper, the polyaluminum sulfate early strength alkali-free liquid accelerator is prepared using polymeric aluminum sulfate, diethanolamine, magnesium sulfate heptahydrate and nano-silica. The influence of this agent on the setting time of fresh cement paste and compressive strength of the corresponding cement mortar is determined. Thermogravimetric analysis curves, X-ray diffraction and scanning electron microscopy images are obtained to investigate the mechanism. Findings show that the initial setting time and the final setting time of cement paste are 2 min 30 s and 7 min 25 s. The compressive strengths of cement mortar cured for 1 d, 28 d and 90 d are 2.4 MPa, 52.2 MPa and 54.3 MPa respectively. Additionally, the corresponding flexural strengths are 3.4 MPa, 9.8 MPa, 11.8 MPa. When the mass rate of accelerator is 7%, the mechanical strengths of cement mortar are the highest. The additions of fly ash and blast furnace slag can affect the mechanical of cement mortar mixed with accelerator. When the mass ratio of the fly ash and blast furnace slag is 15%, the mechanical strengths of cement mortar reach the highest. Moreover, the hydration heat release rate of cement is increased by the accelerator and the corresponding time of hydration heat peak is decreased by the accelerator. The accelerator can decrease the amount of needle-like hydration products and improve the compactness. The mechanical strengths are improved by consuming a large amount of Ca(OH)2 and forming more compact hydration products. It is recommended that the optimum dosage range of the polyaluminum sulfate early strength alkali-free liquid accelerator is 7%. [ABSTRACT FROM AUTHOR]

We aimed to investigate the role of microRNA-5100 (miRNA-5100) in oral squamous cell carcinoma (OSCC) and its underlying mechanisms. Material/Methods: The expression of miR-5100 and suppressor of cancer cell invasion (SCAI) in OSCC cell lines were examined. A luciferase reporter assay was applied to confirm the combination between miR-5100 and SCAI. Then, miR-5100 inhibitor or small hairpin RNA (shRNA)-SCAI were transfected into cells. Cell Counting Kit-8 assay was executed for testing cell proliferation ability. Flow cytometry assay was exploited for measuring cell cycle. Invasion and migration of OSCC cells were assessed using Transwell assay and wound healing assay. The expression of proteins were detected using western blotting. The results demonstrated that the level of miR-5100 was upregulated while SCAI was downregulated in OSCC cells. SCAI was verified as a direct target of miR-5100. MiR-5100 silencing suppressed proliferation of OSCC cells, increased cells in the G1 and G2 phases, and reduced those in the S phase, which was reversed after transfection with shRNA-SCAI. Moreover, miR-5100 inhibitor downregulated the expression of cyclin-dependent kinase-2 (CDK-2) and cyclinD1, accompanied by upregulation in p27 expression, whereas SCAI silencing had the opposite results. The invasion and migration abilities of OSCC cells were reduced after treatment with miR-5100 inhibitor, whereas SCAI silencing suppressed the effects of miR-5100 inhibitor on OSCC cell behaviors. These findings suggested that miR-5100 silencing inhibit proliferation, invasion and migration of OSCC cells via upregulating the expression of SCAI, which provides theoretical basis and treatment strategies for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Immune infiltrates have been increasingly recognized as robust prognostic factors for human cancer. Here, we developed and validated a seven‐immune‐feature‐based prognostic score (7IFBPS) for patients with oral squamous cell carcinoma (OSCC) after curative resection. Fourteen immune features regarding detailed locations and densities of seven types of tumor‐infiltrating immune cells (TIIs) were characterized in clinical samples from 269 eligible patients in three independent cohorts by immunohistochemistry coupled with digital quantitation. Optimal cutoff values for individual immune features were yielded using X‐tile software. The 7IFBPS was constructed by Kaplan–Meier and Cox regression model in training cohort and verified in testing, validation and combined cohorts. Concordance index (C‐index), receiver operating characteristics and calibration curves were employed to define the performance of 7IFBPS in prognostic prediction. High CD3 IM (invasive margin), CD3 CT (center of tumor), CD8 CT, CD45RO IM, CD45RO CT, FOXP3 IM and FOXP3 CT significantly associated with improved survival. The 7IFBPS score was calculated using the formula: 1.041 × CD3 IM + 1.24 × CD3 CT + 1.701 × CD8 CT + 1.127 × CD45RO IM + 1.348 × CD45RO CT + 1.089 × FOXP3 IM + 1.483 FOXP3 CT. High 7IFBPS significantly associated with improved survival in all cohorts and served as an independent prognostic predictor. The C‐index of 7IFBPS for predicting survival was 0.668 (95% CI, 0.609–0.726). Calibration curves for survival probability showed good agreement between prediction by 7IFBPS and actual observation. Collectively, our findings established the 7IFBPS as a novel powerful prognostic classifier for resectable OSCC. It holds potentials to be incorporated into current prognostic regime to better patient stratification. What's new? Current prognostic biomarkers for oral squamous cell carcinoma (OSCC) remain far from optimal. Comprehensive and simultaneous characterization of tumor‐infiltrating immune cells (TIIs) in solid tumors has been proposed as a novel and robust approach to predict clinical outcome. However, comprehensive immune profiling and its clinical significance in OSCC have been incompletely explored thus far. Here, a 7‐immune‐feature‐based prognostic score (7IFBPS) for patients with OSCC after curative resection was developed and validated as a novel powerful prognostic classifier. The integrative immune classifier holds great potential to be incorporated into current prognostic approaches to improve patient stratification, treatment‐decision making, and follow‐up scheduling. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of non-apoptotic cell death that mainly results from the iron-dependent lethal accumulation of lipid peroxidation products. Here, we defined differentially expressed genes between control and RSL3-treated osteosarcoma cells as ferroptosis-associated genes (FAGs). These FAGs were then subjected to weighted gene correlation network analysis (WGCNA), and we found that the turquoise module, containing 71 FAGs, was markedly related to the patient's vital status. After that, FAGs in the turquoise module were utilized to construct a prognostic multigene ( COL5A2 , HOXB4 , and UNC5B ) signature for risk stratification in osteosarcoma. Validation in internal and external cohorts indicated the accuracy and clinical applicability of this signature in predicting the prognosis of patients with osteosarcoma. Univariate and multivariate Cox regression analyses suggested that the signature-derived risk score is an independent indicator of patient prognosis. Immunological analysis indicated that significant variations in stromal and ESTIMATE scores, as well as tumor purity, were found when the high- and low-risk groups were compared. Regarding immune cell infiltration, the proportion of activated CD4 memory T cells was significantly lower in the high-risk group than that in the low-risk group. The ssGSEA results suggested that CD8 + T, Tfh, and Th1 cell scores were consistently lower in the high-risk group than those in the low-risk group. In terms of immune-related activities, the high-risk group had considerably lower scores for promoting inflammation, T-cell co-inhibition, and T-cell co-stimulation than the low-risk group, indicating the differential immunological state of the high- and low-risk groups. Of the three FAGs included in the signature, the expression of COL5A2 , HOXB4 , and UNC5B was higher in the high-risk groups, and the expression of COL5A2 and UNC5B was negatively associated with patient prognosis. Additionally, the mRNA levels of COL5A2 and HOXB4 were lower and those of UNC5B were higher in RSL3-treated cells than in control cells. In all, we systematically analyzed the transcriptional changes of osteosarcoma cells induced by RSL3 and constructed a novel three-gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment. We also identified COL5A2 , HOXB4 , and UNC5B as potential therapeutic targets and important regulators of ferroptosis in osteosarcoma., 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 © 2022 Zheng, Xia, Wei, Wei and Guo.)

Alternative splicing of pre-mRNAs expands the coding abilities of genomes by generating distinct transcription variants from individual genes. It contributes to the marvelous complexity of the transcriptome in neurons. Given the differential expression of alternative splicing regulators and diversity in alternative splicing programs in neuronal subpopulations, it is urgent and necessary to develop methods to efficiently isolate diverse subgroups of neurons and analyze their transcriptomic diversity. Here, we describe a protocol to isolate RNA from specific neuronal types using a fluorescence-activated cell sorting (FACS)-based method to analyze alternative splicing events in a cell type-specific manner. The method is universally applicable to analyze alternative splicing in fluorescent protein-labeled neuronal types. It was optimized to preserve the transcription state and improve efficiency in cell suspension purification. With our protocol, fluorescent protein-labeled neurons could be efficiently purified. The transcription states suitable for gene expression and alternative splicing analysis could be well-preserved., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)