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Abstract Background Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis. Results We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial–mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM. Conclusions Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.

Objective To investigate the association between RET genotype and disease phenotype in the patients with hereditary medullary thyroid carcinoma (HMTC). Methods A total of 13 patients diagnosed as HMTC and undergoing surgical treatment for thyroid carcinoma in this hospital from March 2015 to September 2019 were analyzed retrospectively with follow-up cutoff at September 2021. The patient risk stratification was performed according to American Thyroid Association (ATA) guidelines. The association between RET genotype and disease phenotype including biochemical results, TNM stage, both biochemical [normal serum calcitonin(CT)] cure and clinical cure was analyzed. Results There were 1 (7.69%) case, 6(46.15%) cases, and 6(46.15%) cases with the highest risk mutation (RET M918T), high-risk mutation (RET C634Y and C634S), and moderate-risk mutation (RET C618G and C611Y), respectively. One case with the highest risk mutation was at TNM stage Ⅳ. There were 4 cases (66.67%) at stageⅠand 2 cases (33.33%) at stage Ⅲ among 6 cases with high-risk mutation. For 6 cases with moderate-risk mutation, stage Ⅰ and stage Ⅱ had 1 case(16.67%) respectively, and stage Ⅲ and stage Ⅳ with 3 cases (50%) and 1 case (16.67%) respectively. The highest preoperative CT and carcinoembryonic antigen were detected in 1 case with highest risk mutations (20 000 ng/L, 831.8 μg/L), and those lower in 6 cases with moderate-risk mutations (1 221.4 ng/L, 62.3 μg/L). The lowest of them were in 6 cases with high-risk mutations (537.7 ng/L, 41.7 μg/L). Similarly, both clinical cure rate and biochemical cure rate were found poorer in the cases with the highest risk mutation, and better in the case with high-risk mutation, and less better in the cases with moderate-risk mutation. Conclusions RET gene could be associated with HMTC risk of ATA. The patients of RET genotype with high-risk mutations would have higher clinical cure rate and biochemical cure rate than the cases with moderate-risk mutations.

Aim: Senescence of alveolar type II (AT2) cells is an important driver of pulmonary fibrosis. This study aimed to investigate whether and how dysregulation of hydrogen sulfide (H2S) production affected AT2 cell senescence, and then explored the effect of H2S on the communication between AT2 and fibroblasts. Methods: ICR mice were intratracheally administered with bleomycin (3 mg/kg). Sodium hydrosulfide (NaHS, 28 μmol/kg/d) was intraperitoneally injected for 2 weeks. The H2S‐generating enzyme cystathionine‐β‐synthase (CBS) knockout heterozygous (CBS+/−) mice were used as a low H2S production model. Results: Analysis of microarray datasets revealed downregulation of H2S‐generating enzymes in lung tissues of patients with pulmonary fibrosis. Decreased H2S production was correlated with higher levels of cell senescence markers p53 and p21 in bleomycin‐induced lung fibrosis. CBS+/− mice exhibited increased levels of p53 and p21. The numbers of AT2 cells positive for p53 and p21 were increased in CBS+/− mice as compared to control mice. H2S donor NaHS attenuated bleomycin‐induced AT2 cell senescence both in vivo and in vitro. H2S donor suppressed bleomycin‐induced senescence‐associated secretory phenotype (SASP) of AT2 cells via inhibiting p53/p21 pathway, consequently suppressing proliferation and myofibroblast transdifferentiation of fibroblasts. Mechanically, H2S suppressed p53 expression by enhancing the mouse double‐minute 2 homologue (MDM2)‐mediated ubiquitination and degradation of p53. Conclusion: H2S inactivated p53‐p21 pathway, consequently suppressing AT2 cell senescence as well as cell communication between senescent AT2 cells and fibroblasts. Aberrant H2S synthesis may contribute to the development of pulmonary fibrosis through promoting the activation loop involving senescent AT2 cells and activated fibroblasts. [ABSTRACT FROM AUTHOR]

According to the characteristics of the Flexible job shop scheduling problem the minimum makespan as measures we proposed a distributed particle swarm optimization algorithm aiming to solve flexible job shop scheduling problem. The algorithm adopts the method of distributed ideas to solve problems and we are established for two multi agent particle swarm optimization model in this algorithm it can solve the traditional particle swarm optimization algorithm when making decisions in real time according to the emergencies. Finally some benthmark problems were experimented and the results are compared with the traditional algorithm. Experimental results proved that the developed distributed PSO is enough effective and efficient to solve the FJSP and it also verified the reasonableness of the multi}gent particle swarm optimization model.

The paper analyzed main causes of longitudinal tearing accident of belt conveyor of coal mine, namely belt could be teared by anchor pole, puncheon, waste rock or roller, and proposed some preventing methods for longitudinal tearing of belt conveyor including strengthening routing inspection, using belt with pre-tearing net as far as possible, and setting protecting sensors of pre longitudinal tearing. The paper can provide certain guidance to prevent longitudinal tearing accident of belt conveyor of coal mine.

To evaluate the application of the filter-based model(FBM), the modified RNGκ-ε, the FBM model with different filter sizes are used to simulate the cloud cavitating flows around a cascade hydrofoil. The calculation results are compared with the experimental data. It is shown that the fit filter size FBM turbulence model can capture the detail process of the vortex shedding in the rear part of the cavitating region better, while considering the effect of the turbulence in the cavitation model. The lift force and the drag force are more accordant with the experiment with a suitable filter size. [ABSTRACT FROM AUTHOR]

To assess a modified RNG κ - ε turbulence model, the cloud cavitating flow around a Clark-y hydrofoil is investigated using RNG κ - ε turbulence model with a modified turbulence viscosity coefficient, and the coefficient is related to the vapor and liquid densities in the cavitating region. The time evolutions of the shape of cloud cavities, the lift and drag force around the hydrofoil have been obtained, and compared with experimental results. It is shown that the modified model can predict successfully the characteristics of cavitation and the detailed process of the cavitation shedding. Values of n in the modified coefficient are found to have a strong influence on the cavity length, the vapor volume, the lift and drag force, but no significant effect on the frequency distribution of the dynamics around the foil is observed. [ABSTRACT FROM AUTHOR]

The application of a filter-based model (FBM) for the computations of cavitation flow is studied based on the flow around a cascade hydrofoil. With reference to the largest grid size of the refined region near the hydrofoil, four filters were selected in the FBM model. Through comparison with the results of the experiment and the standard κ - ε model, the effects and selection of the filter size were studied at the aspects of cavity shape and drag prediction. The results shown that the turbulent viscosity correction by the filter function is mainly done at the region of cavity shedding in the rear part of the hydrofoil, and the correction is increased with the decrease of the filter size. Considering the resolving capability of the grid for the turbulence scale, the filter size is proposed to be a value a bit larger than the largest grid size of the refined region. [ABSTRACT FROM AUTHOR]

Background: Autophagy is activated during the pathogenesis of endothelial dysfunction and sepsis-associated acute lung injury (ALI). This study aimed to investigate whether autophagy affected endothelial barrier dysfunction and lung injury in a murine model of lipopolysaccharide (LPS)-induced ALI, and then further clarify whether forkhead box O1 ( FOXO1 ), an autophagy-related transcriptional factor, contributed to autophagy activation and ALI induced by LPS., Methods: Male C57BL/6 mice were treated with LPS (30 mg/kg), and then were allocated to a control group and an LPS group with or without FOXO1 inhibitor (AS1842856) treatment, respectively. Primary cultured mouse lung vascular endothelial cells (MLVECs) were treated with LPS, autophagy inhibitor 3-methyladenine (3-MA), AS1842856, and small interfering RNA (siRNA) targeting autophagy-related gene 5 ( ATG5 ) or FOXO1 . Endothelial autophagic flux was assessed by transfection of MLVECs with red fluorescent protein (RFP)-green fluorescent protein (GFP) tandem fluorescent-tagged LC3 (RFP-GFP-LC3) adenovirus. Endothelial permeability was analyzed by the diffusion of fluorescein isothiocyanate-carboxymethyl (FITC)-dextran through the endothelial monolayer. Evans blue albumin tracer was used to measure the pulmonary transvascular permeability, and hematoxylin and eosin (H&E) staining was used to observe pathological changes in the lung tissues. Immunofluorescence staining was also used to detect the expression of zonula occludens-1 (ZO-1) and FOXO1., Results: This study found autophagy induction in lung tissues of endotoxemic mice and LPS-treated MLVECs, as evidenced by elevated expression of light chain 3 II (LC3-II) and Unc-51-like kinase (ULK1) and autophagic flux. LPS treatment decreased vascular endothelial (VE)-cadherin and ZO-1 expression and increased endothelial permeability in MLVECs, which were significantly alleviated by autophagy inhibitor 3-MA and ATG5 siRNA. It was found that both phosphorylated FOXO1 and FOXO1 were upregulated in the lung tissues of endotoxemic mice and LPS-treated MLVECs. Both FOXO1 inhibitor AS1842856 and FOXO1 siRNA suppressed LPS-induced autophagy and endothelial cell injury in MLVECs. Moreover, FOXO1 inhibition profoundly alleviated autophagy, lung endothelial hyperpermeability, and ALI in endotoxemic mice., Conclusions: This work demonstrated that FOXO1 upregulation is an important contributor to LPS-induced autophagy in pulmonary VE cells. The detrimental effects of FOXO1 in endotoxemia-associated endothelial dysfunction and ALI are partly due to its potent pro-autophagic property. Inhibition of FOXO1 may be a potential therapeutic option for the treatment of ALI., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-5380/coif). All authors report funding from the National Natural Science Foundation of China (Nos. 31871156, 32171124, 81672266, 82072209) and the Shanghai Frontiers Science Research Base of Exercise and Metabolic Health. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

To explore the differences in lipid metabolites in serum of hyperuricemic rats induced by fructose and normal rats by using lipid metabolomics technology, and screen the potential biomarkers related to hyperuricemia. The metabolic fingerprint spectrum of the serum in hyperuricemic rats(model group) and normal rats(control group) was obtained and analyzed by using ultra performance convergence chromatography-tandem-Q-time of flight mass spectrometry(UPC ² -Q/TOF-MS) method and the differences of metabolic spectra between two groups were compared via the multivariate statistical methods to screen differential metabolites. The results indicated that there was significant difference in metabolic spectra between model group and control group, and 11 differential metabolites were screened. Then eight potential biomarkers such as arachidonic acid, palmitic acid, oleic acid and linoleic acid were tentatively identified by using the exact mass number and secondary mass spectrometry(MS/MS spectrum). Therefore, a new research method for lipid metabolomics in serum of hyperuricemic rats induced by fructose was established successfully based on UPC ² -Q/TOF-MS. What's more, it was speculated that the abnormal metabolism of fatty acid might be associated with the pathogenesis of hyperuricemia, which would provide scientific basis for early detection and prevention of hyperuricemia., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This research uses six Agrobacterium rhizogenes R1601, R15384, R1000, A4, R1025 and R1 to infect silymarin explants to induce hairy roots and silibin. All of the six A. rhizogenes can induce Silybum marianum to generate hairy roots and the A. rhizogene A4 shows comparatively high infection on the plant. This research determines the condition to induce silymarin hairy roots by the factors of infection time, pre-culturing, co-culturing and pH value. The fact that MS liquid medium fits the proliferation of silymarin hairy roots is determined. Through PCR molecular identification, it can be seen that the DNA plasmids in the A. rhizogenes are successfully integrated into the genome of transformed roots. Using liquid chromatography, it is determined that the silibin content in silymarin hairy roots is 2.5 times that in the plant In this research, the silymarin hairy roots culturing system is established, which lays a foundation for the study of culturing silymarin hairy roots and producing silibin.