Paeoniflorin mitigates MMP-12 inflammation in silicosis via Yang-Yin-Qing-Fei Decoction in murine models.

BACKGROUND: Silicosis presents a significant clinical challenges and economic burdens, with Traditional Chinese Medicine (TCM) emerging as a potential therapeutic avenue. However, the precise effects and mechanisms of TCM in treating silicosis remain uncertain and subject to debate. OBJECTIVE: The study aims to elucidate the therapeutic role and mechanisms of the Yang-Yin-Qing-Fei Decoction (YYQFD) and its key component, paeoniflorin, in silicosis using a murine model. METHODS: Silicotic mice were treated with YYQFD, pirfenidone (PFD), or paeoniflorin. RAW264.7 cells and mouse lung fibroblasts (MLF) were stimulated with silica, matrix metalloproteinase-12 (MMP-12), or TGF-ß1, followed by treatment with paeoniflorin, PFD, or relevant inhibitors. YYQFD constituents were characterized using High-Performance Liquid Chromatography (HPLC). Lung fibrosis severity was assessed via histopathological examination, micro-CT imaging, lung functions, and Western blot analysis. Transcriptome sequencing and bioinformatics analysis were employed to delineate the gene expression profile and target genes modulated by YYQFD in silicosis. RESULTS: Treatment with YYQFD ameliorated silica-induced lung fibrosis. Transcriptome sequencing identified MMP-12 as a potential common target of YYQFD and PFD. Additionally, a potential pro-inflammatory role of MMP-12, regulated by silica-induced TLR4 signaling pathways, was revealed. Paeoniflorin, one of the most distinctive compounds in YYQFD, attenuated silica-induced MMP-12 increase and its derived inflammatory factors in macrophages through a direct binding effect. Notably, paeoniflorin treatment exerted anti-fibrotic effects by inhibiting MMP-12-derived inflammatory factors and TGF-ß1-induced myofibroblast differentiation in silica-exposed mice. CONCLUSIONS: This study underscores paeoniflorin as one of the most principal bioactive compounds in YYQFD, highlighting its capacity to attenuate lung inflammation driven by macrophage-derived MMP-12 and reduce lung fibrosis both in vivo and in vitro.

The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs/Th1/Th2/Th17/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver.

Inorganic arsenic is a well-established environmental toxicant linked to acute liver injury, fibrosis, and cancer. While oxidative stress, pyroptosis, and ferroptosis are known contributors, the role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in arsenic-induced hepatic immunotoxicity remains underexplored. Our study revealed that acute arsenic exposure prompts differentiation of hepatic dendritic cells (DCs) and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells, alongside increased transcription factors and cytokines. Inorganic arsenic triggered liver redox imbalance, leading to elevated alanine transaminase (ALT), hydrogen peroxide (H2O2), malondialdehyde (MDA), and activation of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway. PINK1-mediated mitophagy was initiated, and its inhibition exacerbates H2O2 accumulation while promoting DCs/Th1/Th2/Treg differentiation in the liver of arsenic-exposed mice. Mitoquinone (MitoQ) pretreatment relieved arsenic-induced acute liver injury and immune imbalance by activating Nrf2/HO-1 and PINK1-mediated mitophagy. To our knowledge, this is the first report identifying PINK1-mediated mitophagy as a protective factor against inorganic arsenic-induced hepatic DCs/Th1/Th2 differentiation. This study has provided new insights on the immunotoxicity of inorganic arsenic and established a foundation for exploring preventive and therapeutic strategies targeting PINK1-mediated mitophagy in acute liver injury. Consequently, the application of mitochondrial antioxidant MitoQ may offer a promising treatment for the metalloid-induced acute liver injury.

OC-STAMP Overexpression Drives Lung Alveolar Epithelial Cell Type II Senescence in Silicosis.

Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.

Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways.

BACKGROUND: Silica-induced inflammatory activation is associated with silicosis and various non-respiratory conditions. The present study was designed to examine the anti-inflammatory effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on lung macrophages and bone osteoclasts after silica inhalation in rats. METHODS: Wistar rats and NR8383 and RAW 264.7 cell lines were used in the present study. The receptor activator of nuclear factor kappa-B ligand (RANKL) and toll-like receptor 4 (TLR4) signaling pathways was measured in the lung tissue of rats or NR8383/RAW 264.7 cells exposed to silica. The microarchitecture of the trabecular bone in the tibia and femur was evaluated in silicotic rats. Furthermore, the roles of Ac-SDKP on silicotic rats, silica-treated NR8383/RAW 264.7 cells, and RANKL-induced osteoclast differentiation were studied. RESULTS: The data indicated that silica inhalation might activate the RANKL and TLR4 signaling pathways in lung macrophages, thus inducing the lung inflammatory and proteolytic phenotype of macrophages and osteoclasts in lung and bone. Ac-SDKP maintained the lung elastin level by inhibiting lung inflammation and macrophage activation via the RANKL and TLR4 signaling pathways. Ac-SDKP also attenuated the reduction in femoral bone mineral density in silicotic rats by inhibiting osteoclast differentiation via the RANKL signaling pathway. CONCLUSION: Our findings support the hypothesis that inhalation of crystalline silica induces activation of lung macrophages and bone osteoclasts via the RANKL and TLR4 signaling pathways. Ac-SDKP has the potential to stabilize lung homeostasis and bone metabolism.

Matrix stiffness regulates α-TAT1-mediated acetylation of α-tubulin and promotes silica-induced epithelial-mesenchymal transition via DNA damage.

Silicosis is characterized by silica exposure-induced lung interstitial fibrosis and formation of silicotic nodules, resulting in lung stiffening. The acetylation of microtubules mediated by α-tubulin N-acetyltransferase 1 (α-TAT1) is a posttranslational modification that promotes microtubule stability in response to mechanical stimulation. α-TAT1 and downstream acetylated α-tubulin (Ac-α-Tub) are decreased in silicosis, promoting the epithelial-mesenchymal transition (EMT); however, the underlying mechanisms are unknown. We found that silica, matrix stiffening or their combination triggered Ac-α-Tub downregulation in alveolar epithelial cells, followed by DNA damage and replication stress. α-TAT1 elevated Ac-α-Tub to limit replication stress and the EMT via trafficking of p53-binding protein 1 (53BP1, also known as TP53BP1). The results provide evidence that α-TAT1 and Ac-α-Tub inhibit the EMT and silicosis fibrosis by preventing 53BP1 mislocalization and relieving DNA damage. This study provides insight into how the cell cycle is regulated during the EMT and why the decrease in α-TAT1 and Ac-α-Tub promotes silicosis fibrosis.This article has an associated First Person interview with the first authors of the paper.

Letrozole and the Traditional Chinese Medicine, Shaofu Zhuyu Decoction, Reduce Endometriotic Disease Progression in Rats: A Potential Role for Gut Microbiota.

We previously showed that the Chinese herbal medicine, Shaofu Zhuyu decoction (SFZYD), shrank the size of endometriotic lesions in rats with endometriosis. We therefore conducted the present study to investigate the effects of letrozole and SFZYD on gut microbiota in endometriotic rats. Rats were divided into four groups: a blank group, model group, letrozole group, and SFZY group. Ectopic lesion size and COX-2 expression in the endometrium and endometriotic lesions were compared, and the community of gut microbiota was detected using 16S rRNA gene sequencing. Both letrozole and SFZYD reduced the size of ectopic lesions as well as lowered the expression of COX-2, thus reducing the inflammatory response. Compared with the blank group, the α-diversity of gut microbiota in endometriotic rats decreased, the Firmicutes/Bacteroidetes ratio increased, and the abundance of Ruminococcaceae was reduced. The α-diversity of gut microbiota in the letrozole group was similar to that in the model group, but the Firmicutes/Bacteroidetes ratio was diminished. The α-diversity in the SFZY group was similar to that in the blank group, the Firmicutes/Bacteroidetes ratio was attenuated, and the abundance of Ruminococcaceae was elevated compared with the model group. These results indicated that the therapeutic mechanisms of both letrozole and SFZYD were related to the restoration of gut microbiota.

Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling.

To identify potential therapeutic targets for pulmonary fibrosis induced by silica, we studied the effects of this disease on the expression of microRNAs (miRNAs) in the lung. Rattus norvegicus pulmonary silicosis models were used in conjunction with high-throughput screening of lung specimens to compare the expression of miRNAs in control and pulmonary silicosis tissues. A total of 70 miRNAs were found to be differentially expressed between control and pulmonary silicosis tissues. This included 41 miRNAs that were upregulated and 29 that were downregulated relative to controls. Among them, miR-292-5p, miR-155-3p, miR-1193-3p, miR-411-3p, miR-370-3p, and miR-409a-5p were found to be similarly altered in rat lung and transforming growth factor (TGF)-ß1-induced cultured fibroblasts. Using miRNA mimics and inhibitors, we found that miR-1193-3p, miR-411-3p, and miR-370-3p exhibited potent anti-fibrotic effects, while miR-292-5p demonstrated pro-fibrotic effects in TGF-ß1-stimulated lung fibroblasts. Moreover, we also found that miR-411-3p effectively reduced pulmonary silicosis in the mouse lung by regulating Mrtfa expression, as demonstrated using biochemical and histological assays. In conclusion, our findings indicate that miRNA expression is perturbed in pulmonary silicosis and suggest that therapeutic interventions targeting specific miRNAs might be effective in the treatment of this occupational disease.

Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex.

The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling. Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO2. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation. Results: Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed. Loss and shedding of primary cilia were also found during silicosis. Treatment of MRC-5 fibroblasts with silica and then transfection of KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3R on ACTA2. Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO2.

MiR-411-3p alleviates Silica-induced pulmonary fibrosis by regulating Smurf2/TGF-ß signaling.

Occupational exposure to silica dust particles was the major cause of pulmonary fibrosis, and many miRNAs have been demonstrated to regulate target mRNAs in silicosis. In the present study, we found that a decreasing level of miR-411-3p in silicosis rats and lung fibroblasts induced by TGF-ß1. Enlargement of miR-411-3p could inhibit the cell proliferation and migration in lung fibroblasts with TGF-ß1 treatment and attenuate lung fibrosis in silicotic mice. In addition, a mechanistic study showed that miR-411-3p exert its inhibitory effect on Smad ubiquitination regulatory factor 2 (Smurf2) expression and decrease ubiquitination degradation of Smad7 regulated by smurf2, result in blocking of TGF-ß/Smad signaling. We proposed that increased expression of miR-411-3p abrogates silicosis by blocking activation of TGF-ß/Smad signaling through decreasing ubiquitination degradation effect of smurf2 on Smad7.

Inhibition of miR-155-5p Exerts Anti-Fibrotic Effects in Silicotic Mice by Regulating Meprin α.

Silicosis is a fatal profession-related disease linked to long-term inhalation of silica. The present study aimed to determine whether meprin α, a master regulator of anti-fibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), is diminished by miR-155-5p in silicotic and control lung macrophages and fibroblasts upon activation. NR8383 macrophages, primary lung fibroblasts, and mouse embryonic fibroblasts were used to evaluate the expression and function of meprin α and miR-155-5p. In vitro meprin α manipulation was performed by recombinant mouse meprin α protein, actinonin (its inhibitor), and small interfering RNA knockdown. Macrophage and fibroblast activation was assessed by western blotting, real-time PCR, matrix deposition, and immunohistochemical staining. The roles of meprin α and miR-155-5p were also investigated in mice exposed to silica. We found that the meprin α level was stably repressed in silicotic rats. In vitro, silica decreased meprin α, and exogenous meprin α reduced activation of macrophages and fibroblasts induced by profibrotic factors. miR-155-5p negatively regulated Mep1a by binding to the 3' untranslated region. Treatment with anti-miR-155-5p elevated meprin α, ameliorated macrophage and fibroblast activation, and attenuated lung fibrosis in mice induced by silica. The sustained repression of meprin α and beneficial effects of its rescue by inhibition of miR-155-5p during silicosis indicate that miR-155-5p/meprin α are two of the major regulators of silicosis.

Interaction of N-acetyl-seryl-aspartyl-lysyl-proline with the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis attenuates pulmonary fibrosis in silicotic rats.

NEW FINDINGS: What is the central question of this study? What are the effects of the antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas axis during the occurrence and progression of silicosis? What is the main finding and its importance? Ac-SDKP inhibited lung fibrosis in rats exposed to silica by activation of the ACE2-angiotensin-(1-7)-Mas axis. Angiotensin-(1-7) potentially promotes Ac-SDKP by increasing the level of meprin α, the major synthetase of Ac-SDKP. Thus, the interaction Ac-SDKP and angiotesin-(1-7) in silicosis could provide a new therapeutic strategy. ABSTRACT: The central role of angiotensin-converting enzyme (ACE) in the occurrence and progression of silicosis has been established. The antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) can be degraded by ACE. The ACE2-angiotensin-(1-7)-Mas axis is protective and acts to counterbalance the detrimental effects of ACE-angiotensin II (Ang II)-Ang II type 1 receptor and exerts antifibrotic effects. Here, we demonstrate an interaction between Ac-SDKP and Ang-(1-7) in the inhibition of collagen deposition and myofibroblast differentiation in rats exposed to silica. Treatment with Ac-SDKP increased the level of ACE2-Ang-(1-7)-Mas in rats or in cultured fibroblasts and decreased the levels of collagen type I and α-smooth muscle actin. Furthermore, exogenous Ang-(1-7) had similar antifibrotic effects and increased the level of meprin α, a major Ac-SDKP synthetase, both in vivo and in vitro. Compared with non-silicotic patients exposed to silica, the level of serum ACE was increased in patients with silicosis phase III; the levels of Ang II and Ang-(1-7) were high in patients with silicosis phase II; and the level of Ac-SDKP was high in the silicosis phase III group. These data imply that Ac-SDKP and Ang-(1-7) have an interactive effect as regulatory peptides of the renin-angiotensin system and exert antifibrotic effects.

Targeting the RAS axis alleviates silicotic fibrosis and Ang II-induced myofibroblast differentiation via inhibition of the hedgehog signaling pathway.

The hedgehog (HH) signaling pathway plays an important role in lung development, but its significance in silicosis is unclear. We showed that in human coal pneumoconiosis autopsy specimens, Sonic Hedgehog (SHH) and the Glioma-associated oncogene homolog transcription factors family (GLI) 1 proteins were up-regulated, whereas Patch-1 (PTC) was down-regulated. The protein levels of SHH, smoothened (SMO), GLI1, GLI2, α-smooth muscle actin (α-SMA) and collagen type Ⅰ (Col Ⅰ) were also elevated gradually in the bronchoalveolar lavage fluid (BALF) of different stages of coal pneumoconiosis patients, dynamic silica-inhalation rat lung tissue and MRC-5 cells induced by Ang II at different time points, whereas the PTC and GLI3 levels were diminished gradually. Ac-SDKP, an active peptide of renin-angiotensin system (RAS), is an anti-fibrotic tetrapeptide. Targeting RAS axis also has anti-silicotic fibrosis effects. However, their roles on the HH pathway are still unknown. Here, we reported that Ac-SDKP + Captopril, Ac-SDKP, Captopril, or Ang (1-7) could alleviate silicotic fibrosis and collagen deposition, as well as improve the lung functions of silicotic rat. These treatments decreased the expression of SHH, SMO, GLI1, GLI2, α-SMA, and Col Ⅰ and increased the expression of PTC and GLI3 on both the silicotic rat lung tissue and MRC-5 cells induced by Ang II. We also reported that Ang II may promote myofibroblast differentiation via the GLI1 transcription factor and independently of the SMO receptor.

Rho GDP dissociation inhibitor α silencing attenuates silicosis by inhibiting RhoA/Rho kinase signalling.

Transforming growth factor-ß1 (TGF-ß1) alters the fibroblast phenotype by promoting transdifferentiation into myofibroblasts, which exhibit the ability to promote collagen synthesis and extracellular matrix (ECM) deposition, thereby playing a significant role in the pathology of silicosis. In this study, we investigated the regulatory mechanisms involved in myofibroblast transdifferentiation. Two-dimensional gel electrophoresis showed that Rho GDP-dissociation inhibitor α (RhoGDIα) was upregulated following myofibroblast transdifferentiation stimulated by TGF-ß1. We hypothesised that RhoGDIα may induce myofibroblast transdifferentiation and thus result in silicosis. Accordingly, the biological significance of RhoGDIα in cell proliferation and apoptosis was investigated by deletion of RhoGDIα in MRC-5 cells. In addition, a mechanistic study showed that fasudil, an inhibitor of the RhoA/Rho kinase (ROCK) signalling pathway, reduced the levels of RhoGDIα, RhoA, and phospho-myosin phosphatase （phospho-MYPT） in MRC-5 cells and silicosis model rats. Knockdown of RhoGDIα inhibited myofibroblast transdifferentiation and collagen deposition through RhoGDIα/RhoA/ROCK signalling in silicosis model mice. Overall, downregulation of RhoGDIα may significantly promote cell apoptosis and inhibit cell growth, resulting in reversal of myofibroblast transdifferentiation by RhoA/ROCK in vitro and in vivo. These data will facilitate further exploration of the potential use of RhoGDIα as a target for silicosis therapy.

An Improved Modified Universal Ultra-Wideband Antenna Designed for Step Frequency Continuous Wave Ground Penetrating Radar System.

Step Frequency Continuous Wave Ground Penetrating Radar (SFCW-GPR), as a tool for nondestructive testing of shallow soil surface targets, the realization of the function of SFCW-GPR is mainly based on the theory of refraction, reflection and scattering of electromagnetic wave in the discontinuity of dielectric constant. So, the UWB antenna system, an important part of SFCW-GPR, becomes more indispensable. In this paper, an improved modified universal antenna is designed, simulated and fabricated. Based on a typical Bow-tie antenna, it is modified by the methods of lumped loads, cavity-backed loading and structure loading. The simulated and measured results show that the UWB antenna has 1.36 GHz bandwidth from 0.64 to 2.0 GHz with three resonant wavelength peaks, and having been modified and improved, the UWB antenna performances including voltage standing-wave ratio (VSWR), input impedance, the boresight gain and current distribution, are much better than the typical Bow-tie antenna. In addition, the results of verification experiment of Step Frequency Continuous Wave (SFCW) show that the antenna can be applied to the working scenarios of SFCW-GPR.

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) attenuates silicotic fibrosis by suppressing apoptosis of alveolar type II epithelial cells via mediation of endoplasmic reticulum stress.

Damage to alveolar epithelial cells (AECs) caused by long-term inhalation of large amounts of silica dust plays a significant role in the pathology of silicosis. The present study was undertaken to investigate the regulatory mechanism(s) involved in type II AEC damage from silicon dioxide (SiO2) as well as the mechanism(s) related to the prevention of silicosis by the antifibrotic tetra peptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). The 2-DE results showed that SiO2 induced endoplasmic reticulum (ER) stress in A549 cells. In addition, typical apoptotic characteristics were observed using a transmission electron microscope (TEM) in A549 cells stimulated by SiO2 and in type II AECs from silicotic rats. Mechanistic study showed that both Ac-SDKP and 4-phenylbutyrate (4-PBA), an inhibiter of ER stress, attenuated GRP78, phosphor-PERK, phosphor-eIF2α, CHOP and Caspase-12 protein expression in A549 cells stimulated by SiO2 and in type II AECs from silicotic rats. Treatment with Ac-SDKP and 4-PBA in vivo effectively inhibited collagen deposition in the lungs of silicotic rats. In summary, ER stress is involved in the apoptosis of type II AECs both in vitro and in vivo. Ac-SDKP effectively suppresses SiO2-induced apoptosis in type II AECs by attenuating the Caspase-12 and PERK/eIF2α/CHOP pathway activation caused by ER stress, thus preventing silicotic fibrosis.

Shaofu Zhuyu Decoction Regresses Endometriotic Lesions in a Rat Model.

The current therapies for endometriosis are restricted by various side effects and treatment outcome has been less than satisfactory. Shaofu Zhuyu Decoction (SZD), a classic traditional Chinese medicinal (TCM) prescription for dysmenorrhea, has been widely used in clinical practice by TCM doctors to relieve symptoms of endometriosis. The present study aimed to investigate the effects of SZD on a rat model of endometriosis. Forty-eight female Sprague-Dawley rats with regular estrous cycles went through autotransplantation operation to establish endometriosis model. Then 38 rats with successful ectopic implants were randomized into two groups: vehicle- and SZD-treated groups. The latter were administered SZD through oral gavage for 4 weeks. By the end of the treatment period, the volume of the endometriotic lesions was measured, the histopathological properties of the ectopic endometrium were evaluated, and levels of proliferating cell nuclear antigen (PCNA), CD34, and hypoxia inducible factor- (HIF-) 1α in the ectopic endometrium were detected with immunohistochemistry. Furthermore, apoptosis was assessed using the terminal deoxynucleotidyl transferase (TdT) deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL) assay. In this study, SZD significantly reduced the size of ectopic lesions in rats with endometriosis, inhibited cell proliferation, increased cell apoptosis, and reduced microvessel density and HIF-1α expression. It suggested that SZD could be an effective therapy for the treatment and prevention of endometriosis recurrence.

Robust Angle Estimation for MIMO Radar with the Coexistence of Mutual Coupling and Colored Noise.

This paper deals with joint estimation of direction-of-departure (DOD) and direction-of- arrival (DOA) in bistatic multiple-input multiple-output (MIMO) radar with the coexistence of unknown mutual coupling and spatial colored noise by developing a novel robust covariance tensor-based angle estimation method. In the proposed method, a third-order tensor is firstly formulated for capturing the multidimensional nature of the received data. Then taking advantage of the temporal uncorrelated characteristic of colored noise and the banded complex symmetric Toeplitz structure of the mutual coupling matrices, a novel fourth-order covariance tensor is constructed for eliminating the influence of both spatial colored noise and mutual coupling. After a robust signal subspace estimation is obtained by using the higher-order singular value decomposition (HOSVD) technique, the rotational invariance technique is applied to achieve the DODs and DOAs. Compared with the existing HOSVD-based subspace methods, the proposed method can provide superior angle estimation performance and automatically jointly perform the DODs and DOAs. Results from numerical experiments are presented to verify the effectiveness of the proposed method.

Dibutyryl-cAMP attenuates pulmonary fibrosis by blocking myofibroblast differentiation via PKA/CREB/CBP signaling in rats with silicosis.

BACKGROUND: Myofibroblasts play a major role in the synthesis of extracellular matrix (ECM) and the stimulation of these cells is thought to play an important role in the development of silicosis. The present study was undertaken to investigate the anti-fibrotic effects of dibutyryl-cAMP (db-cAMP) on rats induced by silica. METHODS: A HOPE MED 8050 exposure control apparatus was used to create the silicosis model. Rats were randomly divided into 4 groups: 1)controls for 16 w; 2)silicosis for 16 w; 3)db-cAMP pre-treatment; 4) db-cAMP post-treatment. Rat pulmonary fibroblasts were cultured in vitro and divided into 4 groups as follows: 1) controls; 2) 10-7mol/L angiotensin II (Ang II); 3) Ang II +10-4 mol/L db-cAMP; and 4) Ang II + db-cAMP+ 10-6 mol/L H89. Hematoxylin-eosin (HE), Van Gieson staining and immunohistochemistry (IHC) were performed to observe the histomorphology of lung tissue. The levels of cAMP were detected by enzyme immunoassay. Double-labeling for α-SMA with Gαi3, protein kinase A (PKA), phosphorylated cAMP-response element-binding protein (p-CREB), and p-Smad2/3 was identified by immunofluorescence staining. Protein levels were detected by Western blot analysis. The interaction between CREB-binding protein (CBP) and Smad2/3 and p-CREB were measured by co-immunoprecipitation (Co-IP). RESULTS: Db-cAMP treatment reduced the number and size of silicosis nodules, inhibited myofibroblast differentiation, and extracellular matrix deposition in vitro and in vivo. In addition, db-cAMP regulated Gαs protein and inhibited expression of Gαi protein, which increased endogenous cAMP. Db-cAMP increased phosphorylated cAMP-response element-binding protein (p-CREB) via protein kinase A (PKA) signaling, and decreased nuclear p-Smad2/3 binding with CREB binding protein (CBP), which reduced activation of p-Smads in fibroblasts induced by Ang II. CONCLUSIONS: This study showed an anti-silicotic effect of db-cAMP that was mediated via PKA/p-CREB/CBP signaling. Furthermore, the findings offer novel insight into the potential use of cAMP signaling for therapeutic strategies to treat silicosis.

Online technique for detecting state of onboard fiber optic gyroscope.

Although angle random walk (ARW) of fiber optic gyroscope (FOG) has been well modeled and identified before being integrated into the high-accuracy attitude control system of satellite, aging and unexpected failures can affect the performance of FOG after launch, resulting in the variation of ARW coefficient. Therefore, the ARW coefficient can be regarded as an indicator of "state of health" for FOG diagnosis in some sense. The Allan variance method can be used to estimate ARW coefficient of FOG, however, it requires a large amount of data to be stored. Moreover, the procedure of drawing slope lines for estimation is painful. To overcome the barriers, a weighted state-space model that directly models the ARW to obtain a nonlinear state-space model was established for FOG. Then, a neural extended-Kalman filter algorithm was implemented to estimate and track the variation of ARW in real time. The results of experiment show that the proposed approach is valid to detect the state of FOG. Moreover, the proposed technique effectively avoids the storage of data.

Online estimation of Allan variance coefficients based on a neural-extended Kalman filter.

As a noise analysis method for inertial sensors, the traditional Allan variance method requires the storage of a large amount of data and manual analysis for an Allan variance graph. Although the existing online estimation methods avoid the storage of data and the painful procedure of drawing slope lines for estimation, they require complex transformations and even cause errors during the modeling of dynamic Allan variance. To solve these problems, first, a new state-space model that directly models the stochastic errors to obtain a nonlinear state-space model was established for inertial sensors. Then, a neural-extended Kalman filter algorithm was used to estimate the Allan variance coefficients. The real noises of an ADIS16405 IMU and fiber optic gyro-sensors were analyzed by the proposed method and traditional methods. The experimental results show that the proposed method is more suitable to estimate the Allan variance coefficients than the traditional methods. Moreover, the proposed method effectively avoids the storage of data and can be easily implemented using an online processor.