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Cryotherapy is a common non-pharmacological method to relieve pain and inflammation. Clinical studies have shown that cryotherapy can reduce postoperative pain after root canal therapy, but the mechanism remains unclear. In this study, we aimed to investigate the underlying molecular mechanisms by which cryotherapy reduces inflammation in lipopolysaccharide (LPS)-stimulated periodontal ligament cells through transcriptome sequencing analysis. We found that cryotherapy significantly reduced the expression of multiple proinflammatory cytokines and chemokines, and NFKB1 was the key regulator down-regulated by cryotherapy. Importantly, we discovered that lncRNA SNHG1 expression level significantly decreased after cold treatment. SNHG1 expression was positively related to NFKB1 while negatively correlated with miR-9-5p, which formed a novel ceRNA regulatory pathway. Knockdown of SNHG1 significantly reduced the expression of NFKB1, IL1B, and IL6, while overexpression of SNHG1 significantly increased the expression of these genes. In conclusion, our study demonstrated that cryotherapy can effectively reduce inflammation in LPS-induced periodontal ligament cells by suppressing the lncRNA SNHG1/miR-9-5p/NFKB1 axis. [ABSTRACT FROM AUTHOR]

Ki67 is a well-known proliferation marker with a large size of around 350 kDa, but its biological function remains largely unknown. The roles of Ki67 in tumor prognosis are still controversial. Ki67 has two isoforms generated by alternative splicing of exon 7. The roles and regulatory mechanisms of Ki67 isoforms in tumor progression are not clear. In the present study, we surprisingly find that the increased inclusion of Ki67 exon 7, not total Ki67 expression level, was significantly associated with poor prognosis in multiple cancer types, including head and neck squamous cell carcinoma (HNSCC). Importantly, the Ki67 exon 7-included isoform is required for HNSCC cell proliferation, cell cycle progression, cell migration, and tumorigenesis. Unexpectedly, Ki67 exon 7-included isoform is positively associated with intracellular reactive oxygen species (ROS) level. Mechanically, splicing factor SRSF3 could promote exon 7 inclusion via its two exonic splicing enhancers. RNA-seq revealed that aldo-keto reductase AKR1C2 is a novel tumor-suppressive gene targeted by Ki67 exon 7-included isoform in HNSCC cells. Our study illuminates that the inclusion of Ki67 exon 7 has important prognostic value in cancers and is essential for tumorigenesis. Our study also suggested a new SRSF3/Ki67/AKR1C2 regulatory axis during HNSCC tumor progression. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with a nucleophosmin 1 (NPM1) mutation is a unique subtype of adult leukemia. Recent studies show that NPM1-mutated AML has high autophagy activity. However, the mechanism for upholding the high autophagic level is still not fully elucidated. In this study, we first identified that tumor protein p53 inducible nuclear protein 2 (TP53INP2) was highly expressed and cytoplasmically localized in NPM1-mutated AML cells. Subsequent data showed that the expression of TP53INP2 was upregulated by fat mass and obesity-associated protein (FTO)-mediated m6A modification. Meanwhile, TP53INP2 was delocalized to the cytoplasm by interacting with NPM1 mutants. Functionally, cytoplasmic TP53INP2 enhanced autophagy activity by promoting the interaction of microtubule-associated protein 1 light chain 3 (LC3) - autophagy-related 7 (ATG7) and further facilitated the survival of leukemia cells. Taken together, our study indicates that TP53INP2 plays an oncogenic role in maintaining the high autophagy activity of NPM1-mutated AML and provides further insight into autophagy-targeted therapy of this leukemia subtype. [ABSTRACT FROM AUTHOR]

Regulatory T (Treg) cells play crucial roles in maintaining immune self-tolerance and immune homeostasis, and closely associated with many human diseases. Recently, Treg cells-derived extracellular vesicles (Treg-EVs) have been demonstrated as a novel cell-contact independent inhibitory mechanism of Treg cells. Treg-EVs contain many specific biological molecules, which are delivered to target cells and modulate immune responses by inhibiting T cell proliferation, inducing T cell apoptosis, and changing the cytokine expression profiles of target cells. The abnormal quantity or function of Treg-EVs is associated with several types of human diseases or conditions, such as transplant rejection, inflammatory diseases, autoimmune diseases, and cancers. Treg-EVs are promising novel potential targets for disease diagnosis, therapy, and drug transport. Moreover, Treg-EVs possess distinct advantages over Treg cell-based immunotherapies. However, the therapeutic potential of Treg-EVs is limited by some factors, such as the standardized protocol for isolation and purification, large scale production, and drug loading efficiency. In this review, we systematically describe the structure, components, functions, and basic mechanisms of action of Treg-EVs and discuss the emerging roles in pathogenesis and the potential application of Treg-EVs in human diseases. [ABSTRACT FROM AUTHOR]

Development of low thermal conductivity and high strength building materials is an emerging strategy to solve the heavy energy consumption of buildings. This study develops sustainable alkali activated materials (AAMs) for structural members from waste expanded polystyrene (EPS) beads and reduced graphene oxide (rGO) to simultaneously meet the thermal insulation and mechanical requirements of building energy conservation. It was found that the thermal conductivity of AAMs with 80 vol.% EPS and 0.04 wt.% rGO (E8–G4) decreased by 74% compared to the AAMs without EPS and rGO (E0). The 28-day compressive and flexural strengths of E8–G4 increased by 29.8% and 26.5% with the addition of 80 vol.% EPS and 0.04 wt.% rGO, compared to the sample with 80 vol.% EPS without rGO (E8). In terms of compressive strength, thermal conductivity, and cost, the efficiency index of E8–G4 was higher than those of other materials. A building model made from AAMs was designed using building information modeling (BIM) tools to simulate energy consumption, and 31.78% of total energy consumption (including heating and cooling) was saved in the building operation period in Harbin City, China. Hence, AAMs made of waste EPS beads and rGO can realize the structural and functional integrated application in the future. [ABSTRACT FROM AUTHOR]

A new generalized optimum strapdown algorithm with coning and sculling compensation is presented, in which the position, velocity and attitude updating operations are carried out based on the single-speed structure in which all computations are executed at a single updating rate that is sufficiently high to accurately account for high frequency angular rate and acceleration rectification effects. Different from existing algorithms, the updating rates of the coning and sculling compensations are unrelated with the number of the gyro incremental angle samples and the number of the accelerometer incremental velocity samples. When the output sampling rate of inertial sensors remains constant, this algorithm allows increasing the updating rate of the coning and sculling compensation, yet with more numbers of gyro incremental angle and accelerometer incremental velocity in order to improve the accuracy of system. Then, in order to implement the new strapdown algorithm in a single FPGA chip, the parallelization of the algorithm is designed and its computational complexity is analyzed. The performance of the proposed parallel strapdown algorithm is tested on the Xilinx ISE 12.3 software platform and the FPGA device XC6VLX550T hardware platform on the basis of some fighter data. It is shown that this parallel strapdown algorithm on the FPGA platform can greatly decrease the execution time of algorithm to meet the real-time and high precision requirements of system on the high dynamic environment, relative to the existing implemented on the DSP platform.