miR-455-3p regulates lymphangiogenesis in silicosis by regulating VEGF-C/VEGFR3.

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

Ultrasensitivity Detecting AChE through "Covalent Assembly" and Signal Amplification Strategic Approaches and Applied to Screen Its Inhibitor.

An ultrasensitivity detecting assay for acetylcholinesterase (AChE) activity was developed based on "covalent assembly" and signal amplification strategic approaches. After hydrolyzing thioacetylcholine by AChE and participation of thiol in a self-inducing cascade accelerated by the Meldrum acid derivatives of 2-[bis(methylthio) methylene] malonitrile (CA-2), mercaptans triggered an intramolecular cyclization assembly by the probe of 2-(2,2-dicyanovinyl)-5-(diethylamino) phenyl 2,4-dinitrobenzenesulfonate (Sd-I) to produce strong fluorescence. The limit of detection for AChE activity was as low as 0.0048 mU/mL. The detection system also had a good detecting effect on AChE activity in human serum and could also be used to screen its inhibitors. By constructing a Sd-I@agarose hydrogel with a smartphone, a point-of-care detection of AChE activity was achieved again.

Organophosphate Level Evaluation for the Poisoning Treatment by Enzyme Activation Regeneration Strategy with Oxime-Functionalized ZIF-8 Nanoparticles.

In this work, two nanometal-organic frameworks (NMOFs) of ZIF-8-1 and ZIF-8-2 were designed and synthesized with a "missing linker" defects strategy by using Oxime-1 and Oxime-2 as coligands, respectively. ZIF-8-2 exhibited an excellent performance in comparison to that of ZIF-8-1 in activating and regenerating the activity of BChE suppressed by demeton-S-methyl (DSM) and could rapidly detoxify DSM in poisoned serum samples within 24 min. Additionally, the synthesized fluorescence probe of IND-BChE with high quantum yields, large Stokes shifts, and superior water solubility could be used for the detection of both butyrylcholinesterase (BChE) and DSM in a lower LOD of 0.63 mU/mL (BChE) and 0.086 µg/mL (DSM). By the difference in fluorescent intensity of IND-BChE with and without ZIF-8-2, a highly linear relationship of IND-BChE with DSM concentration was found (R2 = 0.9889), and the LOD was 0.073 µg/mL. In addition, an intelligent detection platform of ZIF-8-2@IND-BChE@agarose hydrogel combined with a smartphone formed a point-of-care test for DSM -poisoned serum samples and also realized satisfactory results. Unlike other detection methods of nerve agents, this assay first combined an NMOF reactivator for detoxification and detection of BChE enzyme activity and then quantification of OP nerve agents, which was of great significance in treatment of organophosphate poisoning.

Exploration on the Value of Circulation Quality Control Intervention Mode in Percutaneous Coronary Intervention in Patients with Coronary Heart Disease and Chronic Heart Failure.

BACKGROUND: Patients with coronary heart disease (CHD) often have other diseases due to organ dysfunction, among which chronic heart failure (CHF) is the most common. Percutaneous coronary intervention (PCI) is the mainstream method for the treatment of such diseases. Because most of the patients are the elderly and the functions of various organs are declining, it is necessary to implement scientific and efficient management methods. OBJECTIVE: To explore the application value of circulation quality control intervention (CQCI) mode in PCI of patients with CHD and CHF. Time: From June 2021 to June 2023. METHODS: The clinical data of 197 CHD patients with CHF were retrospectively analyzed, and 14 patients who did not meet the inclusion criteria were excluded. According to different perioperative management methods, the remaining cases were divided into the reference group (RG, receiving routine clinical management) and observation group (OG, receiving routine clinical management and CQCI). The cardiac function indexes and emotional state before and after management were compared between the two groups, and the quality of life in two groups was compared. RESULTS: In this study, 100 patients were included in the RG and 83 patients were included in the OG finally. Compared with the RG, the OG had lower levels of left ventricular end systolic diameter and left ventricular end-diastolic diameter after management (p < 0.05), while the OG had significantly higher left ventricular ejection fraction level (p < 0.001). The OG had overtly higher clinical satisfaction than the RG (p < 0.05). After management, the Hospital Anxiety and Depression Scale score in the OG were distinctly lower than those in the RG (p < 0.001). After management, the OG had significantly higher scores of physiological field, psychological field, social relationship and environmental field than the RG (p < 0.001). CONCLUSION: The application of CQCI mode in the perioperative period of PCI has certain benefits for improving the cardiac function of patients. At the same time, this program can also improve the quality of life of patients to a certain extent, which is helpful to accelerate postoperative rehabilitation.

A Single-Centre, Retrospective Research Evaluation of the Effect of Extended Intervention Model Based on Case Management of Treatment Compliance and Cardiac Function on Patients with Chronic Heart Failure.

OBJECTIVE: To explore the effect of case management-based extended intervention model on treatment compliance and cardiac function in patients with chronic heart failure. METHODS: This study retrospectively analysed the clinical data of 203 patients with chronic heart failure at Xingtai Third Hospital from January 2019 to January 2022. In accordance with different intervention programs, the patients were divided into a study group (SG, n = 102) and a reference group (RG, n = 101). The SG received the extended intervention model based on case management, and the RG adopted the conventional intervention model. Comparison was conducted on the treatment compliance, cardiac function, activity of daily living scale (ADL) scores and readmission rates in both groups. RESULTS: After intervention, the SG showed higher treatment compliance (p < 0.05), lower heart rate, higher left ventricular ejection fraction, ratio of transmitral peak rapid filling velocity to transmitral peak atrial filling velocity at mitral orifice and six-minute walk distance (p < 0.001) and significantly lower ADL score and readmission rates than the RG (p < 0.05). CONCLUSION: The extended intervention model based on case management positively influences the treatment compliance of patients with chronic heart failure and continuously improves patients' cardiac function, reduces the readmission rate, enhances daily living ability, comprehensively increases clinical efficacy and benefits patients for a long period.

miR-29a-3p Regulates Autophagy by Targeting Akt3-Mediated mTOR in SiO2-Induced Lung Fibrosis.

Silicosis is a refractory pneumoconiosis of unknown etiology that is characterized by diffuse lung fibrosis, and microRNA (miRNA) dysregulation is connected to silicosis. Emerging evidence suggests that miRNAs modulate pulmonary fibrosis through autophagy; however, its underlying molecular mechanism remains unclear. In agreement with miRNA microarray analysis, the qRT-PCR results showed that miR-29a-3p was significantly decreased in the pulmonary fibrosis model both in vitro and in vivo. Increased autophagosome was observed via transmission electron microscopy in lung epithelial cell models and lung tissue of silicosis mice. The expression of autophagy-related proteins LC3α/ß and Beclin1 were upregulated. The results from using 3-methyladenine, an autophagy inhibitor, or rapamycin, an autophagy inducer, together with TGF-ß1, indicated that autophagy attenuates fibrosis by protecting lung epithelial cells. In TGF-ß1-treated TC-1 cells, transfection with miR-29a-3p mimics activated protective autophagy and reduced alpha-smooth muscle actin and collagen I expression. miRNA TargetScan predicted, and dual-luciferase reporter experiments identified Akt3 as a direct target of miR-29a-3p. Furthermore, Akt3 expression was significantly elevated in the silicosis mouse model and TGF-ß1-treated TC-1 cells. The mammalian target of rapamycin (mTOR) is a central regulator of the autophagy process. Silencing Akt3 inhibited the transduction of the mTOR signaling pathway and activated autophagy in TGF-ß1-treated TC-1 cells. These results show that miR-29a-3p overexpression can partially reverse the fibrotic effects by activating autophagy of the pulmonary epithelial cells regulated by the Akt3/mTOR pathway. Therefore, targeting miR-29a-3p may provide a new therapeutic strategy for silica-induced pulmonary fibrosis.

Inhibition of Oncogenic Src Ameliorates Silica-Induced Pulmonary Fibrosis via PI3K/AKT Pathway.

Silicosis is a refractory disease. Previous studies indicate that damaged alveolar epithelial cells act as a driver in pulmonary fibrosis. Our results show that epithelial cells that acquire the mesenchymal phenotype are associated with the pathogenesis of silicosis. c-Src kinase, a non-receptor tyrosine kinase, has been shown to be a positive regulator of organ fibrosis, but specific mechanisms remain unclear and rarely researched in silicosis. The activated Phosphatidylinositol-3 kinases/AKT(PI3K/AKT) pathway promotes fibrosis. We aimed to determine whether c-Src regulates fibrosis via the PI3K/AKT signaling pathway in the development of silicosis. C57/BL mice were intratracheally perfused with 10 mg silica suspension to establish a model of silicosis. In vivo, silica particles induced lung fibrosis. The profibrotic cytokine transforming growth factor-ß1 (TGF-ß1) exhibited a high expression in pulmonary fibrosis. The phosphorylated c-Src protein was increased and the PI3K/AKT pathway was activated in model lung tissue. In vitro, silica increased the expression of TGF-ß1- and TGF-ß1-induced mesenchymal phenotype and fibrosis in a mouse epithelial cells line. siRNA-Src inhibited the c-Src, the phosphorylation of the PI3K/AKT pathway, and the mesenchymal phenotype induced by TGF-ß1. LY294002, a specific inhibitor of PI3K, suppressed the phosphorylation of PI3K/AKT but did not affect Src activation. SU6656, a selective Src inhibitor, attenuated fibrosis in silicosis model. In summary, c-Src promotes fibrosis via the PI3K/AKT pathway in silica-induced lung fibrosis, and Src kinase inhibitors are potentially effective for silicosis treatment.

[The causal relationship between gut microbiota and male reproductive and sexual health].

OBJECTIVE: The purpose of this study was to use the MR method to explore the causal relationship between 211 gut microbiota and male reproductive and sexual health. METHODS: The MiBioGen alliance published genome-wide association study (GWAS) related genetic variation data was used as instrumental variables (IVs) for gut microbiota, and the Finngen biobank GWAS related genetic variation data was used as IVs for male infertility, abnormal sperm, sexual dysfunction, erectile dysfunction, and testicular dysfunction. The inverse variance-weighted (IVW) method was used as the MR analysis method, the results were evaluated according to the odds ratio and 95% confidence interval of the effect measures, and data sensitivity analysis was performed. RESULTS: The results showed that 6 types of gut microbiota were related to male infertility, 12 types were related to abnormal sperm, 5 types were related to sexual dysfunction, 4 types were related to erectile dysfunction, and 4 types were related to testicular dysfunction. And there was no abnormality in the data sensitivity analysis. CONCLUSION: The intestinal microbiota is closely related to male reproductive and sexual health.

Lead Tellurite Crystals BaPbTe2O6 and PbVTeO5F with Large Nonlinear-/Linear-Optical Responses due to Active Lone Pairs and Distorted Octahedra.

The exploration of nonlinear-/linear-optical crystal materials with high performance is an extremely difficult research project. Herein, the two new lead tellurite crystals BaPbTe2O6 and PbVTeO5F were successfully obtained through a facile hydrothermal synthesis strategy. BaPbTe2O6 lies in the noncentrosymmetric (NCS) and chiral orthorhombic space group P212121, featuring a unique ∞1[PbTe2O6] chain consisting of the PbO4 and TeO3 building units, while PbVTeO5F belonging to the centrosymmetric (CS) orthorhombic space group Pbca manifests a 2D layer made up of ∞1[PbO4F2] chains and novel [V2Te2O10F2] clusters. Further, a systematic analysis of lead tellurites finds that the coordination geometries of the Pb atom exert a considerable influence on the connection modes of Pb-O and Te-O building units. BaPbTe2O6 shows a great second-harmonic-generation (SHG) effect of ∼5× the benchmark KH2PO4 (KDP) and a large optical birefringence of 0.086 at 590 ± 3 nm. PbVTeO5F demonstrates a remarkably larger birefringence of 0.142 at 590 ± 3 nm, benefiting from the introduction of the VO5F octahedral unit. Theoretical studies reveal that the large SHG and birefringence in BaPbTe2O6 can be attributed to TeO3 and PbO4 polyhedra with active lone pairs, while the remarkably enlarged birefringence in PbVTeO5F is attributable to the highly distorted octahedral VO5F. The functional orientations of active building units may offer a practical insight into the design of the desired optical functional materials.

The significance of serum S100 calcium-binding protein A4 in silicosis.

BACKGROUND: Silicosis is a chronic occupational pulmonary disease characterized by persistent inflammation and irreversible fibrosis. Considerable evidences now indicate that S100 calcium-binding protein A4 (S100A4) has been associated with fibrotic diseases. However, the role of S100A4 in silicosis is still unclear. METHODS: In this study, serum levels of S100A4, transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in patients with silicosis (n = 42) and control group (CG, n = 12) were measured by ELISA. S100A4 expression in lung tissues and primary alveolar macrophages (AMs) of mice with and without silicosis was detected by immunohistochemistry (IHC)/real-time PCR. The correlations between S100A4 and cytokines or lung function were assessed by Spearman's rank correlation analyses. RESULTS: Compared with CG, the levels of S100A4 were significantly increased in silicosis patients (70.84 (46.22, 102.46) ng/ml vs (49.84 (42.86, 60.02) ng/ml). The secretions of TGF-ß1, CTGF, IL-6 and TNF-α in silicosis group were significantly higher than that in control group (p < 0.05). Serum S100A4 levels were positively correlated with TGF-ß1 and IL-6, while were negatively correlated with lung function parameters including percentage of predicted forced vital capacity (FVC%pre), maximum vital capacity (Vcmax), deep inspiratory capacity (IC) and peak expiratory flow at 75% of vital capacity (PEF75). In receiver operating characteristic (ROC) analyses, S100A4 > 61.7 ng/ml had 63.4% sensitivity and 83.3% specificity for silicosis, and the area under the curve (AUC) was 0.707. Furthermore, immunostaining of lung tissues showed the accumulation of S100A4-positive cells in the areas of nodules of silicotic mice. The mRNA expression of S100A4 in the lung tissues and AMs of silicotic mice were significantly higher than controls. CONCLUSION: These data suggested that increased S100A4 might contribute to the pathogenesis of silicosis.

The regulatory effect of pulmonary lymphatic drainage on silicosis fibrosis.

Silicosis is a fibrotic disease caused by long-term inhalation of SiO2 particles that currently has no effective treatment. Earlier studies have suggested that pulmonary lymphatic vessels play a key role in the transport of silica but have not address the long-term effects of altered pulmonary lymphatic drainage on silicosis. Here, we investigated the impact of impaired pulmonary lymphatic drainage on silicosis. In the past, lymphatic drainage disorders were established mainly through the use of VEGF inhibitors. For the first time, we established a model of pulmonary lymphatic drainage disorder by ligating the thoracic duct in rats. Impaired pulmonary lymphatic drainage was found to aggravate inflammation and oxidative damage in silicosis rats and accelerate silicosis progression. Next, we investigated the effect of pulmonary lymphatic drainage on silicosis. We have demonstrated the effect of sodium tanshinone IIA sulfonate(STS) on lymphangiogenesis, which revealed that STS promotes lymphangiogenesis and can delay inflammation, oxidative damage, and fibrosis progression in silicosis rats by promoting the pulmonary lymphatic drainage response, and this effect is mediated by the VEGFR-3/PI3K/AKT signaling pathway. These findings suggest that pulmonary lymphogenesis plays an important role in silicosis pathogenesis, and targeted intervention in pulmonary lymphangiogenesis may be a potential strategy for treating of silicosis in the future.

Silicon, an important exposure marker in vivo in silicosis research.

PURPOSE: The degree of silicosis exposure is closely related to the progress of silicosis. At present, we use animal and human studies to explore whether silicon can be an important exposure marker in the development of silicosis. METHODS: Rats were randomly divided into 2 groups: (1) controls; and (2) silicosis. Rats in the silicosis group were killed at 4, 8, 12, 16, 24 h, 3, 7, 14, 21, and 28 days. Hematoxylin-eosin (HE) and immunohistochemistry (IHC) were performed to observe the histomorphology of lung tissue. The expression levels of CC16 and SP-D were detected using ELISA kits. In addition, we conducted a population study. Workers who have been selected to work in an iron mine for more than 1 year as research objects. The population was divided into four groups: silicosis exposure group (workers exposed to silica dust for more than 1 year in an iron mine were selected); patients group (silicosis patients); observation group (evidence of disease not meeting formal diagnostic criteria) and control group. Both the levels of trace silicon in the urine and blood of rats and human subjects were measured with ICP-MS. RESULTS: Serum levels of silicon were immediately increased in rats exposed to silicon dust. Similarly, our population study revealed that the silicon level in the silica exposure group and the observing group (exposed but no obvious symptoms) were significantly increased over that of the control group (P < 0.05). In subjects with extended exposure to silica, the serum and urine silicon level in exposed workers appeared to rapidly increase, reaching its peak in 1-5 years, followed by a gradual decline thereafter. Workers exposed to dust for less than 10 years were divided into subgroups by 2-year limit. The levels of serum silicon, urine silicon, TGF-ß1, and TNF-α were significantly higher than that of control group. CONCLUSION: Changes of the serum levels of silicon occurred earlier than the expression of cytokines such as TNF-α, TGF-ß1, CC16, and SP-D. The level of silicon in workers rapidly increased after exposure to silica, and the change occurred before the expression of TGF-ß1 and TNF-α. As a whole, the findings suggest that determining the level of silicon in vivo might be an effective exposure marker in the diagnosis and pathogenesis of silicosis.

MiR-186-3p attenuates tumorigenesis of cervical cancer by targeting IGF1.

BACKGROUND: Mounting evidence in the cancer literature suggests that microRNAs (miRNAs) influence the progression of human cancer cells by targeting protein-coding genes. How insulin-like growth factor 1(IGF1) and miR-186-3p contribute to the development of cervical cancer (CC) remains unclear. This study examined the regulatory roles of miR-186-3p and IGF1 in CC development. METHODS: Gene expression levels were determined by qRT-PCR. Proliferation, migration, and apoptosis of CC and normal cells were determined by MTT, Transwell, and caspase-3 activity assays, respectively. Dual-luciferase reporter activity and RNA pull-down assays were performed to identify the target gene of miR-186-3p. RESULTS: IGF1 was the target of miR-186-3p. The expression of miR-186-3p inhibited cell proliferation and migration abilities of CC cell lines, but induced the apoptosis rate of CC cells. IGF1 could restore the inhibitory effects of miR-186-3p on the proliferation, migration, and apoptosis abilities of CC cells. Experimental results revealed that miR-186-3p could inhibit IGF1 expression, thereby reducing the viability of CC cells. CONCLUSIONS: The data suggest that targeting of IGF1 by miR-186-3p could be crucial in regulating the progression of CC.

Increased secretion of VEGF-C from SiO2-induced pulmonary macrophages promotes lymphangiogenesis through the Src/eNOS pathway in silicosis.

Silicosis, a type of lung inflammation and fibrosis caused by long-term inhalation of SiO2 particles, lacks effective treatment currently. Based on the results of our previous animal experiments, in lungs of SiO2-induced silicosis rats, a large number of lymphatic vessels are generated in the early stage of inflammation, which is of great significance for the removal of dust and inflammatory mediators. Here, the molecular mechanism of lymphangiogenesis is further studied. Vascular endothelial growth factor (VEGF-C) is a key pro-lymphangiogenic factor, and its elevated expression is closely related to lymphangiogenesis. In this investigation, we demonstrated that the protein level of VEGF-C was differentially expressed in bronchoalveolar lavage fluid (BALF) and alveolar macrophages (AM) in silicosis patients and healthy controls. We further stimulated human monocyte-macrophage line U937 with SiO2, collected the culture supernatants as conditioned medium (CM) for culturing lymphatic endothelial cells (LECs) in vitro, and observed the expression of VEGF-C in the supernatant and its effect on LEC tube formation. The results showed that both CM and single VEGF-C recombinant protein stimulation significantly enhanced LEC proliferation [(1.80 ± 0.18), (1.73 ± 0.16)], chemotaxis [chemotactic cell number (101.40 ± 13.83), (93.40 ± 9.61)], and tube formation [tube number (32.20 ± 7.26), (25.00 ± 6.25); branch number (77.20 ± 6.80), (84.60 ± 7.90)], whereas CM treated with VEGF-CmAb inhibited the proliferation (1.37 ± 0.17), chemotaxis [chemotactic cell number (57.40 ± 8.62)], and tube formation [tube number (7.40 ± 1.85); branch number (47.20 ± 13.44)] of LECs. In addition, CM and VEGF-C can promote the expression of vascular endothelial growth factor receptor 3 (VEGFR-3) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in LECs, which may further mediate lymphangiogenesis by up-regulating the Src/eNOS downstream signaling molecular pathway. This study is the first to clarify the molecular mechanism of pulmonary lymphangiogenesis in silicosis and may point in the direction of eventual treatments, surveillance, and regulation at a molecular level.

Silica dust exposure induces pulmonary fibrosis through autophagy signaling.

Silicosis is a well-acknowledged occupational lung disease caused by inhalation of a large amount of free silica dust during the production period and eventually a considerable negative impact on the patients' quality of life. Autophagy exerts a critical influence on immune and inflammatory responses during the pathogenesis of pulmonary fibrosis. In this study, we sought to determine whether autophagy is involved in silicosis's pathogenesis and how it may affect pulmonary cellular physiology. In the animal experiments, we found persistent activation of autophagy in the development of pulmonary fibrosis, which was also accompanied by tumor necrosis factor and transforming growth factor expression increased. Therefore, the autophagy signaling pathway may regulate the inflammatory response and affect the progression of fibrosis. Further, in vitro experiments, we used LY294002, RAPA, and N-acetylcysteine (NAC) intervened autophagy. Our results showed that PI3K/Akt/mTOR signaling pathway is involved in the autophagy changed mediated by SiO2 exposed, and autophagy might play a protective role in the progression of pulmonary fibrosis. Additionally, NAC's effect is not apparent on SiO2 -mediated autophagy through the PI3K/Akt/mTOR signaling pathway, but it can reduce the inflammatory response on NR8383 cells mediated by SiO2-exposed. Nevertheless, it's interesting that NAC can reduce the inflammatory response on NR8383 cells mediated by SiO2 -exposed. Taken together, our data demonstrated that SiO2 -exposed can induce pulmonary fibrosis along with autophagy both in vivo and in vitro, NAC could alleviate the inflammatory response NR8383 cells by SiO2 -exposed through non PI3K/Akt/mTOR signaling pathway, and the specific mechanism of its action needs further studying.

Decreased Soluble Receptor of Advanced Glycation End Product Levels Correlated with Inflammation in Silicosis.

Silicosis is a devastating disease caused by inhalation of silica dust that leads to inflammatory cascade and then scarring of the lung tissue. Increasing evidences indicate that soluble receptor for advanced glycation end products (sRAGE) is involved in inflammatory diseases. However, no data on the possible relationship between sRAGE and inflammation of silicosis are available. In this study, serum from subjects with silicosis (n = 59) or from healthy controls (HC, n = 14) was analyzed for the secretion of sRAGE, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and oxidized low-density lipoprotein (ox-LDL). The associations between sRAGE and cytokines and ox-LDL and lung function were assessed by Pearson's correlation analyses. Mean levels of serum sRAGE were lower in silicosis than those in controls (p < 0.05). The subjects who had a longer term of occupational exposure had higher levels of sRAGE (p < 0.05). The secretion of TNF-α, IL-1ß, IL-6, TGF-ß1, and ox-LDL was significantly higher in the silicosis group than that in the HC group (p < 0.05). Furthermore, the levels of sRAGE were negatively correlated with TNF-α, IL-6, IL-1ß, and ox-LDL. There is no correlation between sRAGE and TGF-ß1 and lung function. The optimal point of sRAGE for differentiating silicosis from healthy controls was 14250.02 pg/ml by ROC curve analysis. A decrease in serum sRAGE and its association with inflammatory response might suggest a role for sRAGE in the pathogenesis of silicosis.

Hierarchical Suppression Based Matched Filter for Hyperspertral Imagery Target Detection.

Target detection in hyperspectral imagery (HSI) aims at extracting target components of interest from hundreds of narrow contiguous spectral bands, where the prior target information plays a vital role. However, the limitation of the previous methods is that only single-layer detection is carried out, which is not sufficient to discriminate the target parts from complex background spectra accurately. In this paper, we introduce a hierarchical structure to the traditional algorithm matched filter (MF). Because of the advantages of MF in target separation performance, that is, the background components are suppressed while preserving the targets, the detection result of MF is used to further suppress the background components in a cyclic iterative manner. In each iteration, the average output of the previous iteration is used as a suppression criterion to distinguish these pixels judged as backgrounds in the current iteration. To better stand out the target spectra from the background clutter, HSI spectral input and the given target spectrum are whitened and then used to construct the MF in the current iteration. Finally, we provide the corresponding proofs for the convergence of the output and suppression criterion. Experimental results on three classical hyperspectral datasets confirm that the proposed method performs better than some traditional and recently proposed methods.

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.

Increased Concentrations of Extracellular Histones in Patients with Tuberculous Pleural Effusion.

BACKGROUND Extracellular histones have recently been suggested as critical mediators in many inflammatory diseases. However, the role of extracellular histones in tuberculous pleural effusion (TPE) is unclear. The goal of this study was to explore the potential involvement of extracellular histones in patients with TPE. MATERIAL AND METHODS Samples of pleural effusion and peripheral blood were obtained from 58 patients with tuberculosis. Extracellular histones were determined in both TPE and serum samples. Moreover, the biomarkers for cellular damage, inflammatory cell activation, and systemic inflammation including lactate dehydrogenase (LDH), myeloperoxidase (MPO), S100A8/A9, as well as multiple inflammatory cytokines were measured. RESULTS Extracellular histone levels were significantly elevated in TPE (4.762 mg/mL [3.336, 7.307]) and serum samples (1.502 mg/mL [1.084, 2.478]) from tuberculosis patients as compared with the serum (0.585 mg/mL [0.285, 0.949]) from healthy controls. Notably, extracellular histones in TPE were also much higher than in serum of patients (P=0.002). LDH, MPO, and S100A8/A9 levels were all increased in TPE, along with a remarkable elevation of various cytokines. A correlation analysis showed that extracellular histones were positively associated with LDH, MPO, and S100A8/A9, and a panel of inflammatory cytokines in TPE. CONCLUSIONS These results suggest that high concentrations of extracellular histones are markedly present in TPE, which may play an inflammatory role towards the progression of tuberculosis.

Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective, multicenter, randomized controlled study in China.

BACKGROUND: Clofazimine (Cfz) has shown activity against Mycobacterium tuberculosis, including multidrug-resistant (MDR) strains in vitro and in animal studies. Here we evaluate the clinical efficacy and tolerability of using Cfz to treat MDR tuberculosis in China. METHODS: We enrolled 105 patients who had sputum culture-positive MDR tuberculosis in 6 major tuberculosis specialty hospitals in China. Patients were randomly assigned to either the Cfz therapy group (n = 53) or control group (n = 52). Patients in the 2 groups were given 21 months of individual-based chemotherapy regimens based on medication history and drug susceptibility test results. The Cfz therapy group regimens incorporated 100 mg of Cfz once daily for 21 months. RESULTS: Three patients in each group discontinued therapy because of side effects or other reasons. Sputum culture conversion to negative was earlier in patients who received Cfz compared with controls (P = .042 by log-rank test). Chest computed tomography showed cavitary changes in 46 patients in the Cfz therapy group and 45 in the control group. Cavity closure was earlier in patient who received Cfz compared with controls (P = .047 by log-rank test). The treatment success rate in the Cfz group was 73.6%, higher than that in control group (53.8%; P = .035). Side effects in skin only occurred in the Cfz group. The rates of skin discoloration and ichthyosis were 94.3% and 47.2%, respectively. CONCLUSIONS: Using Cfz to treat MDR tuberculosis promotes cavity closure, accelerates sputum culture conversion, and improves treatment success rates.