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Improving coal resource mining rates has long been a focus of coal industry research. The gob-side entry retaining by roof cutting (GERRC) is a new coal mining technology that has gained popularity in China due to its high mining rate and safety. Based on the GERRC technology, the precise technical procedure is elaborated, and the fundamental idea of pressure relief is explored through creating a structural mechanics model of the surrounding rock in this paper. The results of mechanical analysis show that the primary mechanism of roof pressure release is to weaken the integrity of the roof, thereby reducing the ultimate bending moment of the rock stratum. In addition, an additional strategy for pressure release is suggested in this research, involving the weakening of the roof rock by the creation of dense pressure-released holes. The results of the engineering field experimentation demonstrate that the dense pressure-released holes can completely replace the conventional blasting technology of the past to achieve the effect of releasing the roof pressure, thus avoiding the use of hazardous and challenging-to-obtain explosives and demonstrating safety, reliability, and feasibility.

Objective: Exploring the effectiveness of miR-30b-5p-loaded PEG-PLGA nanoparticles (NPs) for the treatment of heart failure and the underlying mechanism.Methods: PEG-PLGA characteristics with different loading amounts were first examined to determine the loading, encapsulation, and release of miR-30b-5p from NPs. The effects of miR-30b-5p NPs on cardiac function and structure were assessed by immunofluorescence, echocardiography, HE/Masson staining, and TUNEL staining. The effects of NPs on the expression of factors related to cardiac hypertrophy and inflammation were examined by RT-PCR and western blotting, and the mechanism of miR-30b-5p treatment on heart failure was explored by dual luciferase reporter assay and RT-PCR.Results: The size of PEG-PLGA NPs with different loading amounts ranged from 200 to 300 nm, and the zeta potential of PEG-PLGA NPs was negative. The mean entrapment efficiency of the NPs for miR-30b-5p was high (81.8 ± 2.1%), and the release rate reached 5 days with more than 90% release. Distribution experiments showed that NPs were mainly distributed in the heart and had a protective effect on myocardial injury and cardiac function. Compared with a rat model of cardiac failure and miR-30b-5p-non-loaede NP groups, the expression of cardiac hypertrophy markers (ANP, BNPβ-MHC) and inflammatory factors (IL-1β, IL-6) were significantly decreased. Dual luciferase reporter assay assays indicated that miR-30b-5p exerted its effects mainly by targeting TGFBR2.Conclusion: PEG-PLGA NPs loaded with miR-30b-5p improved cardiac function, attenuated myocardial injury, and regulated the expression of factors associated with cardiac hypertrophy and inflammation by targeting TGFBR2.

To improve the observation accuracy and robustness of the sensorless control of an interior permanent magnet synchronous motor (IPMSM), a sliding mode observer based on the super twisting algorithm (STA-SMO) with adaptive parameters estimation control is proposed, as parameter mismatches are considered. First, the conventional sliding mode observer (CSMO) is analyzed. The conventional exponential approach law produces a large chattering phenomenon in the back EMF estimation, which causes a large observation error when filtering the chattering through the low-pass filter. Second, a high-order approach law of the super twisting algorithm is introduced to observe the rotor position and speed estimation, which uses the integral function to eliminate the chattering of the sliding mode. Third, an adaptive parameter estimation control (APEC) is presented to enhance the observation accuracy caused by parameter mismatches; the motor parameter adaptive law of the APEC is designed by Lyapunov’s stability law. Finally, the proposed method not only reduces both the chattering and the low-pass filter, but it also enhances accuracy and robustness against parameter mismatches, as discussed through simulations and experiments.

Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4+ T cells. HSP65-mediated inhibition of RCT was assessed by evaluating ABCA1, ABCG1, SR-BI, PPAR-γ, and liver X receptor-α expression. A dose-dependent relationship was found between the levels of these proteins and the suppression of cholesterol efflux. Stimulation of Lck-silenced T cells with ionomycin resulted in a decrease in intracellular calcium levels. Treatment of Jurkat cells with PP2, an inhibitor of Src family kinase, inhibited calcium-induced, but not PMA-induced, ERK phosphorylation. NF-κB activation in response to PMA was minimally inhibited in cells stimulated with PP2. HSP65 failed to trigger downstream ERK or JNK phosphorylation or to activate NF-κB or protein kinase C-γ in Lck-silenced cells. Additionally, elevation of intracellular calcium was also impaired. However, HSP65 significantly enhanced cholesterol efflux and decreased cellular cholesterol content by inducing the expression of cholesterol transport proteins in Lck-silenced cells. The treatment of Jurkat cells with PP2 also inhibited cell proliferation and promoted RCT. In conclusion, Lck is a key molecule in the TCR signaling cascade that inhibits cholesterol efflux and upregulates intracellular cholesterol ester content in T cells. Our results demonstrate that the immune response plays a previously unrecognized role in RCT.

Hypoxia-induced cardiomyocyte apoptosis contributes significantly to the development of numerous cardiac diseases, such as ischemic heart disease, heart failure, etc. Promoting cell survival by inhibiting apoptosis is one of the available strategies to attenuate cardiac dysfunction caused by cardiomyocyte loss. Previous studies have been demonstrated that miR-138 and lipocalin-2 (Lcn2) play important roles in cardiomyocyte apoptosis and survival. We presently determined whether Lcn2 is a target gene of miR-138 involved in hypoxia-induced cardiomyocyte apoptosis. Firstly, mimics of miR-138 were transfected into HL-1 cells to investigate its effect on cell apoptosis. Using 3-(4,5-dimethyl-thiazol-2-y1) 2,5-diphenyl tetrazolium bromide (MTT) and Annexin V-FITC/PI flow cytometer assays, over-expression of miR-138 significantly enhanced the cell growth and significantly attenuated the cell apoptosis in hypoxic conditions. Dual-luciferase reporter gene and western blot results confirmed Lcn2 was a direct target of miR-138. Then, the recombinant plasmid, pcDNA3.1/Lcn2 was transfected into the HL-1 cells that over-expressed miR-138. We further observed that the over-expression of Lcn2 diminished the protection of miR-138 over-expression from hypoxia-induced cell survival and apoptosis. In conclusion, our study demonstrated that up-regulation of miR-138 inhibits the hypoxia-induced cardiomyocyte apoptosis via down-regulating the pro-apoptotic gene expression of Lcn2.

Purpose: To prepare and characterize buccal transmucosal delivery system of enalapril maleate for overcoming its low bioavailability, and hence provide improved therapeutic efficacy and patient compliance. Methods: Transmucosal drug delivery systems of enalapril maleate were formulated as buccal films by solvent casting technique using polyvinylpyrrolidone K90, hydroxypropyl methylcellulose, sodium carboxymethylcellulose (high viscosity). The films were evaluated for film weight, thickness, folding endurance, drug content uniformity, surface pH, in vitro residence time, in vitro drug release and ex-vivo permeation. Results: All the formulations showed high drug content (96.45 to 98.49 %). Those with good swelling showed good residence time. In vitro drug release was highest for films prepared with high viscosity grade sodium carboxymethylcellulose (SCMC- HV,F2), releasing 92.24 % of drug in 1.5 h) followed by F4 (containing polyvinyl pyrrolidone K-90 1 % w/v and SCMC (HV) 1 % w/v). Ex-vivo drug permeation at the end of 10 h was 82.24 and 89.9 % for F2 and F4, respectively. Conclusion: Prompt drug release was obtained from the formulation (F2) containing SCMC 2 % w/v with 10 mg enalapril. However, on the basis of the highest swelling and residence time, and controlled drug release, formulation F4 (containing PVP K-90 and SCMC HV) would be suitable for the development of buccal film for effective therapy of cardiac diseases. Keywords: Cardiac disease, Transmucosal, Buccal films, Enalapril maleate, Drug release, Ex-vivo permeation

Serum amyloid P-component (SAP) contributes to host defense and prevents fibrosis. Macrophages are the most abundant inflammatory cell type in atherosclerotic plaques. In the present study, using3H-cholesterol-labeled counting radioactivity assay, we demonstrated that the apoAI-mediated cholesterol efflux in RAW264.7 macrophages was increased by SAP treatment in a time- and dose-dependent manner. We analyzed global gene expression changes upon SAP treatment using RNA sequencing. As a result, a total of 175 differentially expressed genes were identified, of which 134 genes were downregulated and 41 genes were upregulated in SAP treated cells compared to control cells. Quantitative RT-PCR analysis confirmed decreased expression of 5 genes and an increase in expression of 1 gene upon SAP treatment. Gene ontology analysis showed that genes involved in response to stimulus were significantly enriched in differentially expressed genes. Beyond protein-coding genes, we also identified 8 differentially expressed long noncoding RNAs. Our study may provide new insights into mechanisms underlying the functional role of SAP in macrophages.