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Objective: To investigate whether there is a difference in the efficacy of intra-articular injection of tumor necrosis factor (TNF) inhibitor and triamcinolone acetonide (HA) in rheumatoid arthritis (RA) patients with recurrent synovitis after the first intra-articular injection of HA. Methods: RA patients who relapsed 12 weeks after the first HA treatment were enrolled in this study. After joint cavity extraction, recombinant human TNF receptor-antibody fusion protein (TNFR:FC) (25 mg or 12.5 mg) or HA (1 ml or 0.5 ml) was injected then. The changes in the visual analog scale (VAS), joint swelling index, and joint tenderness index before and 12 weeks after reinjection were compared and analyzed. The changes in synovial thickness, synovial blood flow, and fluid dark zone depth before and after reinjection were observed by ultrasound. Results: Forty-two RA patients were enrolled, including 11 males and 31 females, with an average age of 46.79 ± 12.61 years and an average disease duration of 7.76 ± 5.44 years. After 12 weeks of intra-articular injection of HA or TNFR:FC, the VAS scores were significantly lower than those before treatment (P < 0.01). After 12 weeks of injection, the scores of the joint swelling index and tenderness index in both groups were significantly decreased compared with those before treatment. There was no significant difference in synovial thickness under ultrasound in the HA group before and after injection, while the synovial thickness in the TNFR:FC group was significantly improved after 12 weeks (P < 0.01). After 12 weeks of injection, the grade of synovial blood flow signal in both groups decreased significantly compared with that before treatment, especially in the TNFR:FC group. After 12 weeks of injection, the depth of the liquid dark area under ultrasound decreased significantly in the HA group and TNFR:FC group compared with that before treatment (P < 0.01). Conclusion: Intra-articular injection of a TNF inhibitor is an effective method for the treatment of recurrent synovitis after conventional hormone therapy. Compared with HA treatment, it can reduce synovial thickness. Key Points • Intra-articular injection of a TNF inhibitor is an effective method for the treatment of recurrent synovitis after conventional hormone therapy. • Compared with HA treatment, intra-articular injection of biological agents combined with glucocorticoids can not only relieve joint pain but also significantly inhibit joint swelling. • Compared with HA treatment, intra-articular injection of biological agents combined with glucocorticoids cannot only improve synovial inflammation but also inhibit synovial proliferation. • For the treatment of refractory RA synovitis, biological agents combined with glucocorticoid injection are an effective and safe option. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is an important pathological process in many diseases. Wdr5 catalyzes the trimethylation of lysine K4 on histone H3. The effects of Wdr5 on the cardiac fibrosis phenotype and the activation or transformation of cardiac fibroblasts were investigated by Ang-II-infused mice by osmotic mini-pump and isolated primary neonatal rat cardiac fibroblasts. We found that the Wdr5 expression and histone H3K4me3 modification were significantly increased in Ang-II-infused mice. By stimulating primary neonatal rat cardiac fibroblasts with Ang II, we detected that the expression of Wdr5 and H3K4me3 modification were also significantly increased. Two Wdr5-specific inhibitors, and the lentivirus that transfected Sh-Wdr5, were used to treat primary mouse cardiac fibroblasts, which not only inhibited the histone methylation by Wdr5 but also significantly reduced the activation and migration ability of Ang-II-treated fibroblasts. To explore its mechanism, we found that the inhibition of Wdr5 increased the expression of P53, P21. Cut&Tag-qPCR showed that the inhibition of Wdr5 significantly reduced the enrichment of H3K4me3 in the Mdm2 promoter region. For in vivo experiments, we finally proved that the Wdr5 inhibitor OICR9429 significantly reduced Ang-II-induced cardiac fibrosis and increased the expression of P21 in cardiac fibroblasts. Inhibition of Wdr5 may mediate cardiac fibroblast cycle arrest through the Mdm2/P53/P21 pathway and alleviate cardiac fibrosis. [ABSTRACT FROM AUTHOR]

We and others have previously demonstrated that exposure to nickel nanoparticles (Nano-Ni) caused fibrogenic and carcinogenic effects; however, the underlying mechanisms are still not fully understood. This study aimed to investigate the effects of Nano-Ni on epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (BEAS-2B) and its underlying mechanisms since EMT is involved in both cancer pathogenesis and tissue fibrosis. Our results showed that exposure to Nano-Ni, compared to the control Nano-TiO2, caused a remarkable decrease in the expression of E-cadherin and an increase in the expression of vimentin and α-SMA, indicating an inducible role of Nano-Ni in EMT development in human bronchial epithelial cells. HIF-1α nuclear accumulation, HDAC3 upregulation, and decreased histone acetylation were also observed in the cells exposed to Nano-Ni, but not in those exposed to Nano-TiO2. Pretreatment of the cells with a specific HIF-1α inhibitor, CAY10585, or HIF-1α-specific siRNA transfection prior to Nano-Ni exposure resulted in the restoration of E-cadherin and abolished Nano-Ni-induced upregulation of vimentin and α-SMA, suggesting a crucial role of HIF-1α in Nano-Ni-induced EMT development. CAY10585 pretreatment also attenuated the HDAC3 upregulation and increased histone acetylation. Inhibition of HDAC3 with specific siRNA significantly restrained Nano-Ni-induced reduction in histone acetylation and restored EMT-related protein expression to near control levels. In summary, our findings suggest that exposure to Nano-Ni promotes the development of EMT in human bronchial epithelial cells by decreasing histone acetylation through HIF-1α-mediated HDAC3 upregulation. Our findings may provide information for further understanding of the molecular mechanisms of Nano-Ni-induced fibrosis and carcinogenesis. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the molecular mechanisms by which BRD4 play a role in atrial fibrillation (AF). We used a discovery-driven approach to detect BRD4 expression in the atria of patients with AF and in various murine models of atrial fibrosis. We used a BRD4 inhibitor (JQ1) and atrial fibroblast (aFB)-specific BRD4-knockout mice to elucidate the role of BRD4 in AF. We further examined the underlying mechanisms using RNA-seq and ChIP-seq analyses in vitro, to identify key downstream targets of BRD4. We found that BRD4 expression is significantly increased in patients with AF, with accompanying atrial fibrosis and aFB differentiation. We showed that JQ1 treatment and shRNA-based molecular silencing of BRD4 blocked ANG–II–induced extracellular matrix production and cell-cycle progression in aFBs. BRD4-related RNA-seq and ChIP-seq analyses in aFBs demonstrated enrichment of a subset of promoters related to the expression of profibrotic and proliferation-related genes. The pharmacological inhibition of BRD4 in vivo or in aFB-specific BRD4-knockout in mice limited ANG–II–induced atrial fibrosis, atrial enlargement, and AF susceptibility. Our findings suggest that BRD4 plays a key role in pathological AF, at least partially by activating aFB proliferation and ECM synthesis. This study provides mechanistic insights into the development of BRD4 inhibitors as targeted antiarrhythmic therapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Adding fruit tree branches to the compost pile in appropriate proportions is one of the methods used to address the challenge of tobacco waste recycling. However, the effects of different proportions of fruit tree branches on nicotine concentration and microbial diversity during tobacco waste composting have not been reported. In this study, a composting system with tobacco waste, cow dung, and fruit tree branches was established in a laboratory fermenter to assess the impact of adding 10%, 20%, and 30% fruit tree branches on quantity changes. In addition, the relationships between nicotine degradation, compost properties, enzyme activities, and microbial diversities were determined using biochemical assay methods and high-throughput sequencing. The results showed that adding appropriate proportions of fruit branch segments affected changes in physical and chemical properties during composting and promoted tobacco waste compost maturity. Aerobic composting effectively degraded nicotine in tobacco waste. Increased proportions of fruit branch segments led to elevations in nicotine degradation rates and enzyme activities related to lignocellulose degradation. The addition of fruit branches influenced the relative abundance and species of dominant bacteria and fungi at the phylum and genus levels. However, it did not significantly affect the relative abundance of the main bacterial genera involved in nicotine degradation. Nevertheless, it reduced the sensitivity of enzyme activity to nicotine content within heaps, increasing reliance on total nitrogen changes. The results of this study provide a theoretical basis for the utilization of tobacco waste in composting systems and indicate that fruit tree branches can enhance nicotine degradation efficiency during tobacco waste composting. [Display omitted] • Addition of fruit branch segments enhanced tobacco waste compost maturity. • Fruit branch segments led to increased nicotine gradation rates. • Fruit branch segments strengthened lignocellulose degradation enzyme activities. • Fruit branch segments affected the diversity of microorganisms in the heap. • Fruit branch segments reduced enzyme activity sensitivity to nicotine content. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a significant contributor to cardio-cerebrovascular ischemia diseases, resulting in high mortality rates worldwide. During AS, vascular smooth muscle cells (VSMCs) play a crucial role in plaque formation by undergoing phenotypic and osteogenic switching. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has previously been identified as a nuclear regulator that promotes tumorigenesis and metastasis, but its role in regulating VSMCs in AS remains unclear. Our study aimed to investigate the biological functions and specific mechanisms of NEAT1 in regulating VSMCs in AS. We found that NEAT1 was upregulated in the aortas of AS mouse models and dedifferentiated primary VSMCs. Silencing NEAT1 in vitro attenuated the proliferation, migration, and osteogenic differentiation of VSMCs, while NEAT1 overexpression had the opposite effect. Furthermore, NEAT1 promoted VSMC osteogenic differentiation and vascular calcification in both in vivo and in vitro vascular calcification models. We also discovered that NEAT1 directly activates enhancer of zeste homolog 2 (EZH2), an epigenetic enzyme that suppresses the expression of senescence- and antimigration-related genes, by translocating it into the nucleus. CUT&Tag assay revealed that NEAT1 guides EZH2 to the promoters of senescence-related genes (P16, P21, and TIMP3), methylating local histones to reduce their transcription. Our findings suggest that NEAT1 functions in AS by modulating the epigenetic function of EZH2, which enhances the proliferation, migration, and osteogenic differentiation of VSMCs. This study provides new insights into the molecular mechanisms underlying the pathogenesis of AS and highlights the potential of NEAT1 as a therapeutic target of AS. NEW & NOTEWORTHY: Our study demonstrates that the upregulation of long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes proliferation and migration during phenotypic switching of vascular smooth muscle cells in atherosclerosis. We also provide in vivo and in vitro evidence that NEAT1 accelerates vascular calcification. Our findings identified the direct interaction between enhancer of zeste homolog 2 (EZH2) and NEAT1 during atherosclerosis. NEAT1 is necessary for EZH2 to translocate from the cytoplasm to the nucleus, where EZH2 epigenetically inhibits the expression of genes related to senescence and antimigration. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity are among the leading chronic diseases worldwide. Environmental phenols have been renowned as endocrine disruptors that contribute to weight changes; however, the effects of exposure to mixed phenols on obesity are not well established. Methods: Using data from adults in National Health and Nutrition Examination Survey, this study examined the individual and combined effects of four phenols on obesity. A combination of traditional logistic regression and two mixed models (weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR)) were used together to assess the role of phenols in the development of obesity. The potential mediation of cholesterol on these effects was analyzed through a parallel mediation model. Results: The results demonstrated that solitary phenols except triclosan were inversely associated with obesity (P-value < 0.05). The WQS index was also negatively correlated with general obesity (β: 0.770, 95% CI: 0.644–0.919, P-value = 0.004) and abdominal obesity (β: 0.781, 95% CI: 0.658–0.928, P-value = 0.004). Consistently, the BKMR model demonstrated the significant joint negative effects of phenols on obesity. The parallel mediation analysis revealed that high-density lipoprotein mediated the effects of all four single phenols on obesity, whereas low-density lipoprotein only mediated the association between benzophenol-3 and obesity. Moreover, Cholesterol acts as a mediator of the association between mixed phenols and obesity. Exposure to single and mixed phenols significantly and negatively correlated with obesity. Cholesterol mediated the association of single and mixed environmental phenols with obesity. Conclusions: Assessing the potential public health risks of mixed phenols helps to incorporate this information into practical health advice and guidance. [ABSTRACT FROM AUTHOR]

WO 3 thin films fabricated by glancing angle deposition (GLAD) are proposed as excellent electrochromic coatings with favorable ion diffusion. A ∼ 500-nm film prepared by GLAD had a relatively large transmittance modulation. The crystallization structure, surface morphology, chemical state, optical and electrochromic properties of WO 3 thin films were systematically characterized upon annealing treatment. Compared with annealed WO 3 porous nanostructured films, the amorphous as-deposited films exhibited a high coloration efficiency and stable reversibility. Furthermore, the GLAD WO 3 films exhibit the tunable angular selectivity under illumination with p-polarized light because of the birefringence, which could extend the application range of nanostructured films in the electrochromic field. [ABSTRACT FROM AUTHOR]

Autophagy is an evolutionary conserved intracellular degradation/recycling system that is essential for cellular homeostasis. Dysregulation of this process leads to a number of disorders, including pulmonary fibrosis. However, the genetic association between singe nucleotide polymorphisms of autophagy related genes ( ATG s) and the risk of coal workers' pneumoconiosis has not been reported yet. Total of 7 SNPs in ATG s ( ATG16 , ATG12 , ATG5 , ATG10 ) were investigated for their roles in CWP by a case-control study which including 705 CWP patients and 703 control subjects. Genotyping were performed by the Sequenom Mass ARRAY system. Luciferase assays were taken to test the effects of rs26538 C > T on the activity of ATG12 in the promoter. Our data showed that ATG10 rs1864182 GT genotype was associated with a decreased risk of CWP compared with TT genotype (OR = 0.42, 95% CI = 0.33–0.54, P = 0.001). Another 2 SNPs (rs26538, rs510432) were also with the marked decreases in the risk of CWP under recessive models (OR = 0.58, 95% CI = 0.40–0.83, P = 0.002 for rs26538; OR = 0.74, 95% CI = 0.57–0.97, P = 0.040 for rs510432). Luciferase assays in two different cell lines revealed that the rs26538 C > T substitution could reduce the expression of ATG12 . Taken together, we identified three SNPs in ATG s, which implicated the development of CWP. Further studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel HNTs-CTS-PbO 2 composite anode was prepared. • New anode can effectively improve MB removal efficiency. • Degradation of methylene blue follows the pseudo-first-order reaction kinetics. • Elucidation of the degradation mechanism of methylene blue by modified electrodes. Electrode materials are the core of electrocatalytic oxidation technology. Herein, chitosan (CTS)-modified halloysite nanotubes (HNTs) were used for the first time in the doping modification of PbO 2 electrodes by electrodeposition technique, and novel HNTs-CTS-PbO 2 anodes were prepared and used for the electrochemical removal of the thiazine dye methylene blue (MB). The surface structure information, electrochemical properties and oxidation activity of the materials were systematically investigated, and possible degradation pathways of methylene blue were proposed. The results showed that after doping modification, the coating became flatter and denser, and the crystalline shape and crystalline phase of the PbO 2 electrode did not change, but the grain size was significantly reduced; moreover, the modified electrode had higher oxygen precipitation overpotential, larger reactive surface area and lower charge transfer resistance. Additionally, the decolorization degradation of MB by HNTs-CTS-PbO 2 electrode mainly adopts an indirect degradation mechanism and follows the pseudo-first-order kinetic model, which exhibits higher decolorization degradation rate. Analyzing the mechanism of the electrochemical removal of MB from the modified anode, which mainly involves the breakage of C N bonds under the action of ·OH, followed by demethylation and aromatic ring cleavage to obtain monoaromatic amines, sulfonic acids and phenolic compounds, and finally mineralized into inorganic small molecules such as CO 2 and H 2 O. The above results show that HNTs-CTS-PbO 2 anode is a promising candidate in the field of dye wastewater degradation and provide new insights for the application of HNTs. [ABSTRACT FROM AUTHOR]

Air pollution is a public health threat and global epidemiological studies have shown that ambient air pollutants are closely related to various poor health conditions, including neurodegenerative diseases. Here, we evaluated the toxic effects and the underlying mechanisms of fine airborne particulate matter (PM 2.5) on human glioblastoma LN-229 cells. Our results showed that exposure of LN-229 cells to PM 2.5 (≥ 200 μg/mL) significantly reduced cell viability. PM 2.5 exposure increased autophagy, apoptosis, and ROS production in the cells. Pre-treatment with a ROS scavenger, catalase, or depletion of mtDNA (ρ0 cells) abolished PM 2.5 -induced autophagy and apoptosis. PM 2.5 exposure also activated MAPK signals in cells, which were blocked by catalase pre-treatment or mtDNA depletion. Furthermore, inhibition of JNK, but not ERK1/2 or p38, attenuated PM 2.5 -induced autophagy and apoptosis in cells. Finally, suppression of autophagy with Bafilomycin A1 or Beclin 1 siRNA exacerbated PM 2.5 -induced apoptosis, indicating a protective role of autophagy against PM 2.5 -induced apoptosis. Our results demonstrated that exposure of LN-229 cells to PM 2.5 caused autophagy and apoptosis through PM 2.5 -induced ROS generation, mainly by mitochondria, and JNK activation. Autophagy may have a transient protective response in PM 2.5 -induced apoptosis. These findings have important implications for understanding the potential neurotoxicity of PM 2.5. [Display omitted] • PM 2.5 caused a dose- and a time-dependent increase in autophagy and apoptosis in LN-229 cells. • PM 2.5 induced ROS, especially mitochondrial ROS, generation and JNK activation. • Pretreatment of the cells with ROS or JNK inhibitor abolished PM 2.5 -induced autophagy and apoptosis. • PM 2.5 -induced autophagy has a transient protective role on PM 2.5 -mediated apoptosis. [ABSTRACT FROM AUTHOR]

In this study, a visualizable experimental platform of steam ejector oriented towards MED-TVC desalination system is constructed, and the evolution laws of two-phase choking flow and ejector's entrainment performance under various operating parameters are obtained. Further, a matching double-choking theory with consideration of the condensing flow is developed to explain the inherent reason behind these evolution laws. Key results revealed that the formed two-phase choking flows have great effects on ejector's entrainment performance. The primary jet flow choking area linearly increases as the primary steam pressure raises, and the entrainment choking area experiences a small reduction, while the extended flow area marginally increases. Accordingly, the entrainment ratio significantly decreases, while the choking cross-section is slightly shifted upstream. In addition, the primary jet flow choking area considerably decreases with increasing entrainment pressure, but the entrainment choking area is nearly unchanged and the extended flow area increases by more than 8 times. As a result, the entrainment ratio remarkably increases, the choking cross-section migration distances are much larger than that in the case of primary steam pressure varies. A meaningful guide evolves from fact that priority should be given to restrain the condensing flow for achieving a higher energy efficiency of ejector. • Two-phase choking flow regimes inside the steam ejector are visualized and analyzed. • Evolution laws of ejector's choking flow and entrainment performance are obtained. • An improved double-choking theory is developed to explain these evolution laws. • Essential relation between choking flow and entrainment performance is established. • Adverse effects of the two-phase choking flow on ejector performance are discussed. [ABSTRACT FROM AUTHOR]

Heart failure is a serious and life-threatening disease worldwide. Cadherin-11 (Cad-11) is highly expressed in the heart and closely associated with inflammation. There is currently limited understanding on how Cad-11 contributes to cardiac remodeling and its underline molecular mechanism. We found an increased expression of Cad-11 in biopsy heart samples from heart failure patients, suggesting a link between Cad-11 and heart failure. To determine the role of Cad-11 in cardiac remodeling, Cad-11-deficient mice were used in a well-established mouse transverse aortic constriction (TAC) model. Loss of Cad11 greatly improved pressure overload-induced LV structural and electrical remodeling. IL (interleukin)-6 production was increased following TAC in WT mice and this increase was inhibited in cadherin-11−/− mice. We further tested the effect of IL-6 on myocyte hypertrophy and fibrosis in a primary culture system. The addition of hCad-11-Fc to cultured cardiac fibroblasts increased IL-6 production and fibroblast cell activation, whereas neutralizing IL-6 with an IL-6 antibody resulted in alleviating the fibroblast activation induced by hCad-11-Fc. On the other hand, cardiomyocytes were promoted to cardiomyocyte hypertrophy when cultured in condition media collected from cardiac fibroblasts stimulated by hCad-11-Fc.Similarly, neutralizing IL-6 prevented cardiomyocyte hypertrophy. Finally, we found that MAPKs and CaMKII–STAT3 pathways were activated in both hCad-11-Fc stimulated fibroblasts and cardiomyocytes treated with hCad-11-Fc stimulated fibroblast condition medium. IL-6 neutralization inhibited such MAPK and CaMKII-STAT3 signaling activation. These data demonstrate that Cad-11 functions in pressure overload-induced ventricular remodeling through inducing IL-6 secretion from cardiac fibroblasts to modulate the pathophysiology of neighboring cardiomyocytes. [ABSTRACT FROM AUTHOR]

Copper oxide nanoparticles (Nano-CuO) are widely used in medical and industrial fields and our daily necessities. However, the biosafety assessment of Nano-CuO is far behind their rapid development. Here, we investigated the adverse effects of Nano-CuO on normal human bronchial epithelial BEAS-2B cells, especially determined whether Nano-CuO exposure would cause dysregulation of MMP-3, an important mediator in pulmonary fibrosis, and its potential role in epithelial-mesenchymal transition (EMT). Our results showed that exposure to Nano-CuO, but not Nano-TiO2, caused increased ROS generation, MAPKs activation, and MMP-3 upregulation. Nano-CuO-induced ROS generation was not observed in mitochondrial DNA-depleted BEAS-2B ρ0 cells, indicating that mitochondria may be the main source of Nano-CuO-induced ROS generation. Pretreatment of the cells with ROS scavengers or inhibitors or depleting mitochondrial DNA significantly attenuated Nano-CuO-induced MAPKs activation and MMP-3 upregulation, and pretreatment of cells with MAPKs inhibitors abolished Nano-CuO-induced MMP-3 upregulation, suggesting Nano-CuO-induced MMP-3 upregulation is through Nano-CuO-induced ROS generation and MAPKs activation. In addition, exposure of the cells to Nano-CuO for 48 h resulted in decreased E-cadherin expression and increased expression of vimentin, α-SMA, and fibronectin, which was ameliorated by MMP-3 siRNA transfection, suggesting an important role of MMP-3 in Nano-CuO-induced EMT. Taken together, our study demonstrated that Nano-CuO exposure caused mitochondrial ROS generation, MAPKs activation, and MMP-3 upregulation. Nano-CuO exposure also caused cells to undergo EMT, which was through Nano-CuO-induced dysregulation of ROS/MAPKs/MMP-3 pathway. Our findings will provide further understanding of the potential mechanisms involved in metal nanoparticle-induced various toxic effects including EMT and pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: O-GlcNAcylation modification affects multiple physiological and pathophysiolocal functions of cells. Altered O-GlcNAcylation was reported to participate in antivirus response. Stimulator of interferon genes (STING) is an adaptor mediating DNA virus-induced innate immune response. Whether STING is able to be modified by O-GlcNAcylation and how O-GlcNAcylation affects STING-mediated anti-DNA virus response remain unknown. Methods: Metabolomics analysis was used for detecting metabolic alterations in HSV-1 infection cells. Succinylated wheat germ agglutinin (sWGA), co-immunoprecipitation, and pull-down assay were employed for determining O-GlcNAcylation. Mutagenesis PCR was applied for the generation of STING mutants. WT and Sting1−/− C57BL/6 mice (KOCMP-72512-Sting1-B6NVA) were infected with HSV-1 and treated with O-GlcNAcylation inhibitor for validating the role of STING O-GlcNAcylation in antiviral response. Results: STING was functionally activated by O-GlcNAcylation in host cells challenged with HSV-1. We demonstrated that this signaling event was initiated by virus infection-enhanced hexosamine biosynthesis pathway (HBP). HSV-1 (or viral DNA mimics) promotes glucose metabolism of host cells with a marked increase in HBP, which provides donor glucosamine for O-GlcNAcylation. STING was O-GlcNAcylated on threonine 229, which led to lysine 63-linked ubiquitination of STING and activation of antiviral immune responses. Mutation of STING T229 to alanine abrogated STING activation and reduced HSV-1 stimulated production of interferon (IFN). Application of 6-diazo-5-oxonorleucine (DON), an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAcylation, markedly attenuated the removal of HSV-1 in wild type C57BL/6 mice, leading to an increased viral retention, elevated infiltration of inflammatory cells, and worsened tissue damages to those displayed in STING gene knockout mice. Together, our data suggest that STING is O-GlcNAcylated in HSV-1, which is crucial for an effective antiviral innate immune response. Conclusion: HSV-1 infection activates the generation of UDP-Glc-NAc by upregulating the HBP metabolism. Elevated UDP-Glc-NAc promotes the O-GlcNAcylation of STING, which mediates the anti-viral function of STING. Targeting O-GlcNAcylation of STING could be a useful strategy for antiviral innate immunity. [ABSTRACT FROM AUTHOR]

Background: O-GlcNAcylation modification affects multiple physiological and pathophysiolocal functions of cells. Altered O-GlcNAcylation was reported to participate in antivirus response. Stimulator of interferon genes (STING) is an adaptor mediating DNA virus-induced innate immune response. Whether STING is able to be modified by O-GlcNAcylation and how O-GlcNAcylation affects STING-mediated anti-DNA virus response remain unknown. Methods: Metabolomics analysis was used for detecting metabolic alterations in HSV-1 infection cells. Succinylated wheat germ agglutinin (sWGA), co-immunoprecipitation, and pull-down assay were employed for determining O-GlcNAcylation. Mutagenesis PCR was applied for the generation of STING mutants. WT and Sting1−/− C57BL/6 mice (KOCMP-72512-Sting1-B6NVA) were infected with HSV-1 and treated with O-GlcNAcylation inhibitor for validating the role of STING O-GlcNAcylation in antiviral response. Results: STING was functionally activated by O-GlcNAcylation in host cells challenged with HSV-1. We demonstrated that this signaling event was initiated by virus infection-enhanced hexosamine biosynthesis pathway (HBP). HSV-1 (or viral DNA mimics) promotes glucose metabolism of host cells with a marked increase in HBP, which provides donor glucosamine for O-GlcNAcylation. STING was O-GlcNAcylated on threonine 229, which led to lysine 63-linked ubiquitination of STING and activation of antiviral immune responses. Mutation of STING T229 to alanine abrogated STING activation and reduced HSV-1 stimulated production of interferon (IFN). Application of 6-diazo-5-oxonorleucine (DON), an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAcylation, markedly attenuated the removal of HSV-1 in wild type C57BL/6 mice, leading to an increased viral retention, elevated infiltration of inflammatory cells, and worsened tissue damages to those displayed in STING gene knockout mice. Together, our data suggest that STING is O-GlcNAcylated in HSV-1, which is crucial for an effective antiviral innate immune response. Conclusion: HSV-1 infection activates the generation of UDP-Glc-NAc by upregulating the HBP metabolism. Elevated UDP-Glc-NAc promotes the O-GlcNAcylation of STING, which mediates the anti-viral function of STING. Targeting O-GlcNAcylation of STING could be a useful strategy for antiviral innate immunity. [ABSTRACT FROM AUTHOR]

Silicosis is a very serious occupational disease and it features pathological manifestations of inflammatory infiltration, excessive proliferation of fibroblasts and massive depositions of the extracellular matrix in the lungs. Recent studies described the roles of a variety of microRNAs (miRNAs) in fibrotic diseases. Here, we aimed to explore the potential mechanism of miR-542-5p in the activation of lung fibroblasts. To induce a pulmonary fibrosis mouse model, silica suspension and the miR-542-5p agomir were administered to mice by intratracheal instillation and tail vein injection. We found that miR-542-5p was significantly decreased in mouse fibrotic lung tissues and up-regulation of miR-542-5p visually attenuated a series of fibrotic lesions, including alveolar structural damage, alveolar interstitial thickening and silica-induced nodule formation. The down-regulation of miR-542-5p was also observed in mouse fibroblast (NIH-3T3) treated with transforming growth factor β1 (TGF-β1). The proliferation and migration ability of NIH-3T3 cells were also inhibited by the transfection of miR-542-5p mimic. Integrin α6 (Itga6), reported as a cell surface protein associated with fibroblast proliferation, was confirmed to be a direct target of miR-542-5p. The knockdown of Itga6 significantly inhibited the phosphorylation of FAK/PI3K/AKT. In conclusion, miR-542-5p has a potential function for reducing the proliferation of fibroblasts and inhibiting silica-induced pulmonary fibrosis, which might be partially realized by directly binding to Itga6. Our data suggested that miR-542-5p might be a new therapeutic target for silicosis or other pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a special type of pulmonary parenchymal disease, with chronic, progressive, fibrosis, and high mortality. There is a lack of safe, effective, and affordable treatment methods. Qilongtian (QLT) is a traditional Chinese prescription that is composed of Panax notoginseng, Earthworm, and Rhodiola, and shows the remarkable clinical curative effect of PF. However, the mechanism of QLT remains to be clarified. Therefore, we studied the effectivity of QLT in treating Bleomycin (BLM) induced PF mice. 36 C57BL/6 J mice were randomized into the control group, the model group, the low-, medium- and high-dose QLT group, and Pirfenidone group. After establishing a model of pulmonary fibrosis in mice, the control and model groups were infused with a normal saline solution, and the delivery group was infused with QLT. Pulmonary function in the mice from each group was detected. Pulmonary tissue morphologies and collagen deposition were stained by HE and Masson. The content of hydroxyproline (HYP) was detected by alkaline hydrolysis and the mRNA and protein expression of related genes in pulmonary tissues were detected by using q-PCR, ELISA, and Western blot. Our studies have shown that QLT significantly reduced the inflammatory injury, hydroxy-proline content, and collagen deposition of pulmonary tissue in BLM-induced PF mice and down-regulated the cytokine related to inflammation and fibrosis and PF expression on the mRNA and protein level in PF mice. To identify the mechanism of QLT, the Transcriptome was measured and the IL-17 signal pathway was screened out for further research. Further studies indicated that QLT reduced the mRNAs and protein levels of interleukin 17 (IL-17), c–c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 5 (CXCL5), fos-like antigen 1 (FOSL1), matrix metalloproteinase-9 (MMP9), and amphiregulin (AREG), which are inflammation and fibrosis-related genes in the IL-17 signal pathway. The results indicated that the potential mechanism for QLT in the prevention of PF progression was by inhibiting inflammation resulting in the IL-17 signal pathway. Our study provides the novel scientific basis of QLT and represents new therapeutics for PF in clinical. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a chronic, progressive, and fibrotic interstitial lung disease with a high mortality rate. Qi-Long-Tian (QLT) capsule is an herbal formula with great potential for antifibrotic effects, consisting of San Qi (Notoginseng Radix et Rhizoma), Di Long [Pheretima aspergillum (E. Perrier)], and Hong Jingtian (Rhodiolae Crenulatae Radix et Rhizoma), and has been used in clinical practice for many years. To explore the relationship between the effects of Qi-Long-Tian capsule and gut microbiota of PF mice, pulmonary fibrosis model were established by tracheal drip injection of bleomycin. Thirty-six mice were randomly divided into 6 groups: control group (control), model group (model), QLT capsule low dose group (QL), QLT capsule medium dose group (QM), QLT capsule high dose group (QH), and pirfenidone group (PFD). After 21 days of treatment, after pulmonary function tests, the lung tissues, serums, and enterobacterial samples were collected for further analysis. HE staining and Masson’s staining were used to detect changes as the main indicators of PF in each group, and the expression of hydroxyproline (HYP) related to collagen metabolism was detected by and alkaline hydrolysis method. qRT-PCR and ELISA were used to detect the mRNA and protein expressions of pro-inflammatory factors include interleukin 1β (IL-1β), interleukin 6 (IL-6), transforming growth factor β1 (TGF-β1), tumor necrosis factor α (TNF-α) in lung tissues and serums, and the inflammation-mediating factors include tight junction protein (ZO-1, Claudin, Occludin). ELISA was used to detect the protein expressions of secretory immunoglobulin A (sIgA), short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS) in colonic tissues. 16sRNA gene sequencing was used to detect changes in the abundance and diversity of intestinal flora in the control, model, and QM groups, to search for differential genera, and analyze the correlation with inflammatory factors. QLT capsule effectively improved the status of pulmonary fibrosis and reduced HYP. In addition, QLT capsule significantly reduced the abnormal levels of pro-inflammatory factors, including IL-1β, IL-6, TNF-α, and TGF-β in lung tissue and serum, while improving the levels of pro-inflammatory related factors ZO-1, Claudin, Occludin, sIgA, SCFAs, and reducing LPS in the colon. The comparison between the alpha diversity and beta diversity in enterobacteria suggested that the composition of the gut flora in the control, model, and QLT capsule groups were different. QLT capsule significantly increased the relative abundance of Bacteroidia (which might limit the onset of inflammation) and decreased the relative abundance of Clostridia (which might promote inflammation). In addition, these two enterobacteria were closely associated with pro-inflammatory-related indicators and pro-inflammatory factors in PF. All these results suggest that QLT capsule intervenes in pulmonary fibrosis by regulating the differential genera of intestinal flora, increasing immunoglobulin secretion, repairing the intestinal mucosal barrier, reducing LPS entry into the blood, and decreasing inflammatory factor secretion in the serum, which in turn alleviates pulmonary inflammation. This study clarifies the therapeutic mechanism of QLT capsule in PF and provides a theoretical basis for it. It provides a theoretical basis for its further clinical application. [ABSTRACT FROM AUTHOR]

Background. Asthma is a chronic inflammatory disease of the airways with recurrent attacks, which seriously affects the patients' quality of life and even threatens their lives. The disease can even threaten the lives of patients. Sijunzi decoction (SJZD), a classical Chinese medicine formula with a long history of administration, is a basic formula used for the treatment of asthma and demonstrates remarkable efficacy. However, the underlying mechanism has not been elucidated. Materials and Methods. We aimed to integrate network pharmacology and intestinal flora sequencing analysis to study the mechanism of SJZD in the treatment of allergic asthmatic mice. The active compounds of SJZD and their asthma-related targets were predicted by various databases. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify potentially relevant pathways for target genes. Furthermore, the active compound-target and target-signaling pathway network maps were constructed by using Cytoscape 3.8.2. These results were combined with those of the intestinal flora sequencing analysis to study the influence of SJZD on airway inflammation in allergic asthmatic mice. Result. We obtained 137 active compounds from SJZD and associated them with 1445 asthma-related targets acquired from the databases. A total of 109 common targets were identified. We visualized active compound-target and target-signaling pathway network maps. The pathological analysis and inflammation score results suggested that SJZD could alleviate airway inflammation in asthmatic mice. Sequencing analysis of intestinal flora showed that SJZD could increase the relevant abundance of beneficial bacterial genus and maintain the balance of the intestinal flora. The core toll-like receptor (TLR) signaling pathway was identified based on network pharmacology analysis, and the important role TLRs play in intestinal flora and organismal immunity was also recognized. The analysis of the correlation between environmental factors and intestinal flora revealed that beneficial bacterial genera were negatively correlated with TLR2 and positively correlated with the TLR7 expression. Furthermore, they were positively correlated with IFN-γ and IL-10 levels and negatively correlated with IL-4 and IL-17 levels. Conclusion. SJZD alleviated the airway inflammation state in asthmatic mice. The findings suggest that increasing the relevant abundance of beneficial intestinal bacteria in mice with asthma, regulating intestinal flora, interfering with the level of TLR2 and TLR7 expression to adjust the secretion of inflammatory factors, and alleviating asthmatic airway inflammation may be the possible mechanism involved in the treatment of asthma by SJZD, providing a basis for further studies on SJZD. [ABSTRACT FROM AUTHOR]

In this study, the electrodes (PbO 2 , PbO 2 –SiO 2 , PbO 2 –ZrO 2 and PbO 2 –SiO 2 –ZrO 2) were prepared by galvanostatic electrodeposition in a lead nitrate system and used as anode materials for trivalent chromium plating. Physical characterizations show that the successful doping of SiO 2 and ZrO 2 can refine the grain of PbO 2. Electrochemical tests show that the PbO 2 –SiO 2 –ZrO 2 electrode has good electrocatalytic activity and corrosion resistance, which is mainly attributed to the increase of active surface area. In the process of trivalent chromium plating, the initial and increasing range of the cell voltage of the PbO 2 –SiO 2 –ZrO 2 electrode were the lowest, and the amount of hexavalent chromium generated was much smaller than that obtained using the pure PbO 2 electrode, which had obvious advantages in energy savings. This study provides a concise method for PbO 2 electrode modification and provides a reference for the subsequent use of anode materials for trivalent chromium plating and electrodeposition of other metals. [Display omitted] • The PbO 2 –SiO 2 –ZrO 2 electrode doped by nano-oxides was prepared via electrodeposition. • The electrode a large active surface area and excellent electrocatalytic activity. • The functions of SiO 2 and ZrO 2 are to refine grains and promote OER, respectively. [ABSTRACT FROM AUTHOR]

Background: Nickel nanoparticles (Nano-Ni) are increasingly used in industry and biomedicine with the development of nanotechnology. However, the genotoxic and carcinogenic effects of Nano-Ni and the underlying mechanisms are still unclear. Methods: At first, dose–response (0, 10, 20, and 30 μg/mL) and time-response (0, 3, 6, 12, and 24 h) studies were performed in immortalized normal human bronchial epithelial cells BEAS-2B to observe the effects of Nano-Ni on DNA damage response (DDR)-associated proteins and the HIF-1α/miR-210/Rad52 pathway by real-time PCR or Western blot. Then, a Hsp90 inhibitor (1 µM of 17-AAG, an indirect HIF-1α inhibitor), HIF-1α knock-out (KO) cells, and a miR-210 inhibitor (20 nM) were used to determine whether Nano-Ni-induced Rad52 down-regulation was through HIF-1α nuclear accumulation and miR-210 up-regulation. In the long-term experiments, cells were treated with 0.25 and 0.5 µg/mL of Nano-Ni for 21 cycles (~ 150 days), and the level of anchorage-independent growth was determined by plating the cells in soft agar. Transduction of lentiviral particles containing human Rad52 ORF into BEAS-2B cells was used to observe the role of Rad52 in Nano-Ni-induced cell transformation. Nano-Ni-induced DNA damage and dysregulation of HIF-1α/miR-210/Rad52 pathway were also investigated in vivo by intratracheal instillation of 50 µg per mouse of Nano-Ni. gpt delta transgenic mice were used to analyze mutant frequency and mutation spectrum in mouse lungs after Nano-Ni exposure. Results: Nano-Ni exposure caused DNA damage at both in vitro and in vivo settings, which was reflected by increased phosphorylation of DDR-associated proteins such as ATM at Ser1981, p53 at Ser15, and H2AX. Nano-Ni exposure also induced HIF-1α nuclear accumulation, miR-210 up-regulation, and down-regulation of homologous recombination repair (HRR) gene Rad52. Inhibition of or knocking-out HIF-1α or miR-210 ameliorated Nano-Ni-induced Rad52 down-regulation. Long-term low-dose Nano-Ni exposure led to cell malignant transformation, and augmentation of Rad52 expression significantly reduced Nano-Ni-induced cell transformation. In addition, increased immunostaining of cell proliferation markers, Ki-67 and PCNA, was observed in bronchiolar epithelial cells and hyperplastic pneumocytes in mouse lungs at day 7 and day 42 after Nano-Ni exposure. Finally, using gpt delta transgenic mice revealed that Nano-Ni exposure did not cause increased gpt mutant frequency and certain DNA mutations, such as base substitution and small base insertions/deletions, are not the main types of Nano-Ni-induced DNA damage. Conclusions: This study unraveled the mechanisms underlying Nano-Ni-induced cell malignant transformation; the combined effects of Nano-Ni-induced DNA damage and DNA repair defects through HIF-1α/miR-210/Rad52 pathway likely contribute to Nano-Ni-induced genomic instability and ultimately cell transformation. Our findings will provide information to further elucidate the molecular mechanisms of Nano-Ni-induced genotoxicity and carcinogenicity. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia nowadays. The occurrence of AF is closely associated with obesity. Cadherin‐11 (Cad‐11), as a member of the cadherin family, can make a contribution to diet‐induced obesity and it will be informative to know whether Cad‐11 exerts its effects on atrial remodeling and AF vulnerability in a diet‐induced obesity model. In this study, we demonstrated that the expression of Cad‐11 was significantly upregulated in the left atrium of AF patients with obesity and mice following 16 weeks of high‐fat diet (HFD) feeding. Further confirmed that Cad‐11 could regulate the activity of atrial fibroblasts by participating in inducing proinflammatory cytokines production. At animal levels, we found that although there was a lack of statistical difference in body weight, Cad‐11−/− mice could markedly improve impaired glucose tolerance and hyperlipidemia. Adverse atrial structural remodeling, including atrial enlargement, inflammation, and fibrosis provoked by HFD feeding were mitigated in Cad‐11−/− mice. Mechanistically, Cad‐11 activated mitogen‐activated protein kinases and nuclear factor‐κB for interleukin‐6 production in atrial fibroblasts that may contribute to the atrial fibrosis process in obesity‐related AF, suggesting Cad‐11 might be a new therapeutic target for obesity‐related AF. [ABSTRACT FROM AUTHOR]

Gegenqinlian decoction (GD) has been extensively used for the treatment of diarrhea with intestinal dampness-heat syndrome (IDHS) with a satisfying therapeutic effect. The purpose of this study is to clarify the active ingredients and mechanism of GD in the treatment of diarrhea with IDHS. The TCMSP database was used to screen out the active ingredients of the four Chinese herbal medicines in GD, and the targets of the active ingredients were predicted. We selected the targets related to diarrhea through the DisGeNET database, then used the NCBI database to screen out related targets of lactase and sucrase, and constructed the visual network to search for the active ingredients of GD in the treatment of diarrhea and related mechanisms of the targets. Combined with network pharmacology, we screened out 146 active ingredients in GD corresponding to 252 ingredient targets, combined with 328 disease targets in diarrhea, and obtained 12 lactase targets and 11 sucrase targets. The key active ingredients involved quercetin, formononetin, β-sitosterol kaempferol, and wogonin. Furthermore, molecular docking showed that these five potential active ingredients had good affinities with the core targets PTGS2. The active ingredients in GD (such as quercetin, formononetin, and β-sitosterol) may increase the microbial activity of the intestinal mucosa of mice and reduce the microbial activity of the intestinal contents through multiple targets, thereby achieving the effect of treating diarrhea. [ABSTRACT FROM AUTHOR]

In this work, a novel three-dimensional(3D) hierarchical porous lead-carbon composite (Nano-PbO@3DCSHPAC) derived from corn stover biomass was prepared by chemical deposition coupled with pyrolysis to alleviate the problems associated with the high occurrence of the hydrogen evolution reaction (HER) and irreversible sulfation of the negative electrode under a high-rate partial state of charge (HRPSoC). As an additive of negative electrode in lead-carbon battery. PbO, evenly distributed on the Nano-PbO@3DCSHPAC composite, effectively inhibits the HER, acting as a nucleus for the active substance Pb, refining the grains of sponge Pb, and maintaining the high electrochemical active area of the electrode. The Nano-PbO@3DCSHPAC composite with a high specific surface area and porosity possesses good ion channels, provides an ion reservoir, and effectively inhibits irreversible sulfation. As a result, the initial discharge capacity of the battery with Nano-PbO@3DCSHPAC (164 mAh·g-1) is greater than that of the blank battery (109 mAh·g-1). The cycling life of the Nano-PbO@3DCSHPAC battery (10120 cycles) is 9.4 times that of a blank battery (1073 cycles). Our work provides insights into how to regulate the specific surface area and porosity of lead-carbon additives and makes full use of biomass straw to provide new ideas for solving the environmental problems caused by straw incineration. It is the embodiment of the circular economy. [Display omitted] • Nano-PbO@3DCSHPAC composite has high specific surface area and porosity. • The composite maintains the high electrochemically active area of the electrode. • Nano-PbO@3DCSHPAC composite effectively inhibits the hydrogen evolution. • Nano-PbO@3DCSHPAC battery has excellent performance. • Make full use of biomass stover to alleviate the problems caused by incineration. [ABSTRACT FROM AUTHOR]

Lead-carbon batteries (LCBs) possess the dual functions of supercapacitors and lead-acid batteries (LABs), which can meet the demand for renewable energy and in mild hybrid electric vehicles (HEVs) for energy storage and short-term high-rate charging and discharging. With the cycle of high-rate partial state-of-charge (HRPSoC), irreversible sulfation of the positive electrode becomes increasingly prominent and serious, resulting in low discharge capacity and short cycle life. In this study, to reduce the sulfation of the positive plate and improve the battery capacity and cycle life, a lead dioxide nanoparticle-doped graphene oxide (nano-PbO 2 /GO) composite material with dual functions of conducting and nucleating was prepared by a hydrothermal method as a positive electrode additive. The results show that the addition of nano-PbO 2 /GO promotes the formation of a three-dimensional short rod-like structure of PbO 2 nanoparticles in a dendritic arrangement, accelerates the generation of new phases and inhibits the growth of bulk PbSO 4. Moreover, the positive plate with nano-PbO 2 /GO exhibits good electrochemical activity to maintain the stability and reversibility of the electrode redox reaction. Finally, the initial discharge specific capacity of the LCBs with nano-PbO 2 /GO is increased to 153.85 mAh/g, and the HRPSoC cycle life is up to 15658 cycles at a 2 C discharge rate. Overall, the dual functions of nano-PbO 2 /GO greatly alleviate battery sulfation and provide a reference for improving the performance of LCBs by modifying the electrode structure. [Display omitted] • nano-PbO 2 doped graphene composites were successfully prepared. • nano-PbO 2 /GO has electrical conductivity and nucleation. • nano-PbO 2 / GO can deposit nano-PbO 2 and inhibit PbSO 4 growth. • Increased cycle life of batteries with the addition of nano-PbO 2 /GO. • The positive plate forms a micro-nanostructure to mitigate sulfation. [ABSTRACT FROM AUTHOR]

Silica-induced pulmonary fibrosis is a kind of worldwide occupational disease, and there is no effective treatment at present. Peptide therapy has attracted significant attention due to its simple structure, high selectiveness, strong bioactivity, relative safety, and high patient tolerance. In this study, we first confirmed that M10, a 10 amino acid peptide, has anti-fibrotic effects during the early and late stages of silica-induced fibrosis in mouse models and then partly explored the underlying mechanisms in vitro. M10 was detected in both the cell cytoplasm and nuclei. M10 showed no cytotoxicity to pulmonary epithelial cells and fibroblasts at the given concentrations. Functionally, M10 can reverse the silica-induced EMT process in epithelial cells and decrease TGF-β1-stimulated fibroblast activation. Further mechanism investigations supported that M10 can block TGF-β1 signalling by inhibiting phosphorylation of Smad2 protein in vitro and in vivo. All of the results indicate that M10 peptide may be a new method for the treatment of silica-induced pulmonary fibrosis. • M10 peptide prevents silica-induced pulmonary fibrosis in the early fibrotic stage. • M10 attenuates silica-induced pulmonary fibrosis in the late fibrotic stage. • M10 suppresses silica-induced EMT process of the pulmonary epithelial cells. • M10 inhibits TGF-β1-stimulated pulmonary fibroblast activation. • M10 downregulates the expression of phosphorylated Smad2 both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Chronic constipation is a common gastrointestinal dysfunction, but its aetiology and pathogenesis are still unclear. Interestingly, the compositions of the gut microbiota in constipation patients and healthy controls are different. Various studies reported the different gut microbiota alterations in constipation patients, but most studies indicated that constipation patients showed the decreased beneficial bacteria and the reduced species richness of gut bacteria. Besides, the alterations in the gut microbiota may lead to constipation and constipation-related symptoms and the regulation of gut microbiota has a positive effect on gut functional diseases such as constipation. Microbial treatment methods, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can be used to regulate gut microbiota. Increasing evidences have suggested that Chinese medicine (CM) has a good therapeutic effect on chronic constipation. Chinese medicine is well known for its multitarget and multimode effects on diseases as well as less side effects. In previous studies, after the treatment of constipation with CM, the gut microbiota was restored, indicating that the gut microbiota might be the target or important way for CM to exert its efficacy. In this review, we summarized the effects of microbial treatment and CM on the gut microbiota of constipation patients and discussed the relationship between CM and gut microbiota. [ABSTRACT FROM AUTHOR]

Highlights • Post-translational of epigenetic plays a key role in lung fibroblast activation and silica-induced fibrosis. • MiR-125a-3p regulates lung fibroblast activation and silica-induced fibrosis by targeting Fyn. • MiR-125a-3p/Fyn/STAT3signaling pathway is a potential therapeutic approach for pulmonary fibrosis. Abstract Various miRNAs are dysregulated during initiation and progression of pulmonary fibrosis. However, their function remains limited in silicosis. Here, we observed that miR-125a-3p was downregulated in silica-induced fibrotic murine lung tissues. Ectopic miR-125a-3p expression with chemotherapy attenuated silica-induced pulmonary fibrosis. Further in vitro experiments revealed that TGF-β1 effectively decreased miR-125a-3p expression in fibroblast lines (NIH/3T3 and MRC-5). Overexpression of miR-125a-3p blocked fibroblast activation stimulated by TGF-β1. Mechanistically, miR-125a-3p could bind to the 3′-untranslated region of Fyn and inhibit its expression in both mRNA and protein levels, thus causing inactivation of Fyn downstream effector STAT3. Fyn and p-STAT3, as opposed to miR-125a-3p expression, were elevated in silica-induced fibrotic murine lung tissues and TGF-β1-treated fibroblast lines. Furthermore, Fyn knockdown or p-STAT3 suppression effectively attenuated fibroblast activation and ECM production. Taken together, miR-125a-3p is involved in fibrosis pathogenesis by fibroblast activation, suggesting that targeting miR-125a-3p/Fyn/STAT3 signaling pathway could be a potential therapeutic approach for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Silicosis is one of the typical forms of pneumoconiosis characterized by abnormal proliferation of fibroblasts and deposition of extracellular matrix. Recent findings have shown that microRNAs and circular RNAs (circRNAs) are implicated in many diseases. However, the function of noncoding RNAs in pulmonary fibrosis remain to be elucidated. Here, miR-7 was found significantly decreased in silica-treated pulmonary epithelial cells as well as in fibrotic lung tissues of mice. Elevated expression of miR-7 via agomir injection relieved lung fibrosis in vivo. Further molecular study showed that miR-7 played its role against pulmonary fibrosis by blocking epithelial-mesenchymal transition (EMT) progression of human bronchial epithelial cells and A549 cells. Notably, transforming growth factor beta receptor 2 (TGFBR2) was identified as a target gene of miR-7 with bioinformatics tools, which was verified by dual luciferase receptor gene assay in human bronchial epithelial cells and A549 cells. Silica induced elevation of TGFBR2 could be abolished by exogenous expression of miR-7. Furthermore, bioinformatics software indicated that circRNA CDR1as had several binding sites for miR-7. The inhibitory effects of miR-7 on EMT and its target TGFBR2 were suppressed by circRNA CDR1as, which contributed to pulmonary fibrosis. Our studies also revealed overexpressed miR-7 could repress fibrogenesis of lung fibroblasts induced by TGF-β1. Collectively, circRNA CDR1as stimulated by silica could sponge miR-7 to release TGFBR2, plays an important role during pulmonary fibrosis by promoting EMT process. These results indicated that the interaction between miR-7 and circRNA CDR1as may exert important functions and provide potential therapeutic targets in lung fibrotic diseases. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Qiang Zhang, Ting Luo and Dezheng Yuan. Reference 1 Zhang, Q, Luo, T, Yuan, D, Fu, Y, Yuan J. Mechanism study of Qilongtian on pulmonary fibrosis in bleomycin model mice. [Extracted from the article]

Long non-coding RNAs (lncRNAs) are important signal transduction regulators that act by various patterns. However, little is known about the molecular mechanisms of lncRNA related pathways in occupational lung fibrosis. Our previous study found that epithelial-mesenchymal transition (EMT) was one of the key events in silica-induced pulmonary fibrosis. This study showed that the lncRNA-ATB promoted EMT by acting as a miR-200c sponge. miR-200c was identified by miRNA array as a potential target of lncRNA-ATB and verified by dual luciferase reporter gene together with RNA pull-down assays. Moreover, our findings demonstrated that lncRNA-ATB is abundantly expressed during EMT of lung epithelial cells, which contributes to decreased levels of miR-200c. miR-200c targeted ZEB1 to relief silicosis by blocking EMT in vivo and in vitro. The results also suggested M2 macrophages secreted transforming growth factor-β1 (TGF-β1) to induce EMT process by activating lncRNA-ATB in epithelial cells. Collectively, silica-stimulated macrophages secreted TGF-β1 to induce lncRNA-ATB in epithelia cells, promoting EMT by binding with miR-200c and releasing ZEB1. These observations provide further understanding of the regulatory network of silica-induced pulmonary fibrosis and identify new therapeutic targets hopefully. [ABSTRACT FROM AUTHOR]

This study aims to explore the effect of FMT on regulations of dysbacteriosis of pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups: normal control group (K), model control group (MX), and fecal microbiota transplantation group (FMT); each group contained nine rats. The OTU values of the pulmonary and intestinal flora of the MX group decreased significantly compared with the normal control group. After FMT, the OTU value of pulmonary flora increased, while the value of OTU in intestinal flora declined. At the phylum level, FMT down-regulated Proteobacteria, Firmicutes, and Bacteroidetes in the pulmonary flora. At the genus level, FMT down-regulated Pseudomonas, Sphingobium, Lactobacillus, Rhizobium, and Acinetobacter, thus maintaining the balance of the pulmonary flora. Moreover, FMT could change the structure and diversity of the pulmonary and intestinal flora by positively regulating the pulmonary flora and negatively regulating intestinal flora. This study may provide a scientific basis for FMT treatment of respiratory diseases. [ABSTRACT FROM AUTHOR]

Nonstoichiometric titanium dioxide nanostructured thin film (TNF) has attracted a range of interest in the green energy field. In this paper, we introduce the glancing angle deposition (GLAD) technique to produce the amorphous TNFs with discrete nanoscale columnar structures. In order to improve the crystallinity and/or gain the Ti 3+ doped states, amorphous TNFs were annealed at 400 °C in air or H 2 . XRD, SEM, AFM, XPS and PL were used to characterize the crystallization structure morphology, chemical state, PL properties of the TNFs with different annealing conditions. Photocatalytic activities of the samples were reflected by decolorization experiments of methylene blue (MB) solution irradiated by the simulated sunlight light of AM 1.5 G. The photocatalytic activity of amorphous TNF is higher than that of conventional TiO 2 thin film, indicating the prominent properties of nanostructures. Compared with annealing in air, the photocatalytic activity of TiO 2-x nanostructures annealed in hydrogen is further increased and higher. The results demonstrated that Ti 3+ and oxygen vacancies were beneficial and played the dominant role for the enhancement of photocatalytic activity. [ABSTRACT FROM AUTHOR]

Silicosis is a fatal pulmonary fibrotic disorder characterized by accumulation of fibroblasts and myofibroblasts and deposition of extracellular matrix proteins. MiR-449a is a potential mediator of many cellular processes, including cell proliferation, differentiation, and apoptosis. We hypothesized that miR-449a may play a crucial role in the progression of pulmonary fibrogenesis. Here, we described miR-449a as a new autophagy-regulated miRNA. Importantly, miR-449a expression was significantly decreased in lung tissues of mice with silica treatment, and it was similarly expressed in NIH-3T3 and MRC-5 cells stimulated with TGF-β1. The activity of autophagy was inhibited in fibrotic lung tissues and TGF-β1-treated fibroblasts. To investigate the potential effect of miR-449a, we overexpressed miR-449a in mouse models and found that miR-449a significantly reduced both the distribution and severity of lung lesions induced by silica. In addition, miR-449a was observed to induce the activity of autophagy in vivo and in vitro. Notably, Bcl2 was identified as a target of miR-449a. Bcl2 levels were decreased in NIH-3T3 cells upon miR-449a overexpression. Indeed, the Bcl2 3′ UTR contained functional miR-449a responsive sequences. Furthermore, TGF-β1 was observed to increase the expression of Bcl2 via the MAPK/ERK pathway. These results suggest that miR-449a is an important regulator of autophagy, as well as a novel endogenous suppressor of pulmonary fibrosis. Key message: [ABSTRACT FROM AUTHOR]

Compared with pyrometallurgical recycling, hydrometallurgical recycling of spent lead paste has obvious advantages such as energy saving and emission reduction, however, hydrometallurgical recycling of spent lead paste is also characterized by high levels of impurities (e.g.,Fe, Ba and Cu) in the recovered products. In this study, a green process for the conversion of spent lead paste into high-purity lead carbonate is presented. The process consists of four steps: sulfation, desulfurization leaching, distillation and carbonization to obtain high-purity lead carbonate. The details are as follows: (1) Spent lead paste (mainly composed of lead sulfate, lead dioxide, lead oxide and lead monomers) was converted into sulfated lead paste using sulfuric acid, hydrogen peroxide and sodium chloride. (2) The sulfated lead paste was reacted with ammonium acetate to leach the lead while desulfurizing; the leaching rate was reached 99.94% under the conditions of 30 wt% ammonium acetate concentration, 40 °C reaction temperature and 7.5 min reaction time. (3) Glycerol was added to the mother liquor and distilled to obtain a glycerol solution containing lead acetate. (4) Using ammonium carbonate (aq) as a carbonizing agent, reacting for 20 min under the condition that the molar ratio of CO 3 2−/Pb is 1.10 can make more than 99.9% of lead precipitate to obtain high-purity lead carbonate products. (5) The lead carbonate product decomposed into orthorhombic α-PbO at 350 °C. (6) Recovered lead oxide product has better electrochemical performance than commercial lead oxide. This process prepares high-purity lead carbonate and lead oxide products with reduced energy consumption and recycles the spent lead paste. This study provides a feasible technology for green recycling of spent lead paste. [Display omitted] [ABSTRACT FROM AUTHOR]

The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice. Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE. • Gut microbiota signature of un-treated SLE patients was different from that of healthy cohorts. • Fecal transfer from SLE patients to germ free mice caused a series of lupus-like phenotyptic features. • The interplay of gut microbial and histidine metabolism may be one of the mechanisms involved in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]