Identification of idiopathic pulmonary fibrosis hub genes and exploration of the mechanisms of action of Jinshui Huanxian formula.

Idiopathic pulmonary fibrosis (IPF) is a common and heterogeneous chronic disease, and the mechanism of Jinshui Huanxian formula (JHF) on IPF remains unclear. For a total of 385 lung normal tissue samples from the Gene Expression Omnibus database, 37,777,639 gene pairs were identified through microarray and RNA-seq platforms. Using the individualized differentially expressed gene (DEG) analysis algorithm RankComp (FDR < 0.01), we identified 344 genes as DEGs in at least 95 % (n = 81) of the IPF samples. Of these genes, IGF1, IFNGR1, GLI2, HMGCR, DNM1, KIF4A, and TNFRSF11A were identified as hub genes. These genes were verified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in mice with pulmonary fibrosis (PF) and MRC-5 cells, and they were highly effective at classifying IPF samples in the independent dataset GSE134692 (AUC = 0.587-0.788) and mice with PF (AUC = 0.806-1.000). Moreover, JHF ameliorated the pathological changes in mice with PF and significantly reversed the changes in hub gene expression (KIF4A, IFNGR1, and HMGCR). In conclusion, a series of IPF hub genes was identified, and validated in an independent dataset, mice with PF, and MRC-5 cells. Moreover, the abnormal gene expression was normalized by JHF. These findings provide guidance for further exploration of the pathogenesis and treatment of IPF.

Research on Cold Roll Forming Process of Strips for Truss Rods for Space Construction.

In this paper, a new technology for on-orbit cold forming of space truss rods is proposed. For the cold roll forming process of asymmetric cross sections of thin strips, the effects of roll gap and roll spacing on the forming of asymmetric cross sections of strips were investigated using ABAQUS simulation + experiments. The study shows the following. When forming a strip with a specific asymmetric cross section, the stresses are mainly concentrated in corners 2/4/6, with the largest strain value in corner 2. With increasing forming passes, when the roll gap is 0.3 mm, the maximum equivalent strain values are 0.09, 0.24, 0.64 sequentially. Roll gaps of 0.4 mm and 0.5 mm equivalent strain change amplitude are relatively similar, and their maximum equivalent strain values are approximately 0.07,0.15, 0.44. From the analysis of the stress-strain history of the characteristic nodes in corners 2/4/6, it can be seen that the stress and strain changes in the deformation process mainly occur at the moment of interaction between the upper and lower rollers, where the stress type of node 55786 shows two tensile types and one compressive type, the stress type of nodes 48594 and 15928 shows two compressive and one tensile type, and the strain of the three nodes is in accordance with the characteristics of plane strain. When the roll gap is about 0.4 mm, the forming of the strip is relatively good. With increased roll spacing, the strip in the longitudinal stress peak through the rollers shows a small incremental trend, but the peak stresses are 380 Mpa or so. When the roll spacing is 120 mm, the longitudinal strain fluctuation of the strip is the most serious, followed by the roll spacing at 100 mm, and the minimum at 140 mm. Combined with the fluctuation in strip edges under different roll spacings, manufacturing cost and volume and other factors, a roll spacing of 100 mm is more reasonable. It is experimentally verified that when the roll gap is 0.4 mm and the roll spacing is 100 mm, the strip is successfully prepared in accordance with the cross-section requirements. When the rolling gap is 0.3 mm, due to stress-strain concentration, the strip is prone to edge waves in forming. The top of corner 2 of the flange triangular region is susceptible to intermittent tear defects, and the crack extension mechanism is mainly based on the cleavage fracture + ductile fracture.

Study of the Mechanical Properties and Microstructure of Spiral Tubes and Actuators for Controlled Extension Fabricated with Beryllium Bronze Strips.

QBe2.0 strips were used to fabricate spiral tubes and actuators for controlled extension (STACERs) through the winding and stabilization method, which is a novel technique for obtaining STACERs. The raw strips and the STACERs were investigated using tensile tests and SEM for the mechanical properties and fractography observation, employing specialized test equipment for service performance, and via XRD, EBSD, and TEM were used to test the residual stress and microstructure evolution. The tensile strength/elongation for raw strips was 485.8 MPa/60%, while for STACERs, tensile strength increased by 834.67 MPa to 646 MPa, and the elongation rate decreased by 12% to 19.3%. The fractography showed that the fracture mode was ductile. The service performance tests indicated that STACERs obtained under 320 °C had a higher driving force, good pointing accuracy, and high bending stiffness, while the residual stress of raw strips was τxy = -6 MPa; for STACERs obtained between 290 °C and 350 °C, τxy decreased from -5 MPa to -74 MPa, then increased from -74 MPa to 21 MPa, and the optimum fabricating parameter was 320 °C + 2 h. The EBSD results showed that LABs and HABs for raw strips and STACERs at 320 °C + 2 h accounted for 3-97% and 24.5-75.5%, the grain sizes were 7.07 µm and 3.67 µm, and the twin fraction decreased from 57.3% to 31.8%, respectively. The KAM and Schmid factor maps indicated that the STACER was prone to recovering and recrystallizing. Coupled with the EBSD results, the TEM results indicated that the strengthening mechanism for raw strips is twinning strengthening, while that for STACER is grain-refining strengthening with a precipitation of the γ″ phase. It is a meaningful novelty that the relationship between the macro properties and microstructure has been elucidated.

Numerical Study of Ti6Al4V Alloy Tube Heated by Super-Frequency Induction Heating.

Ti6Al4V alloys have a narrow processing window, which complicates temperature control, especially during large-scale production. Therefore, a numerical simulation and experimental study on the ultrasonic induction heating process of a Ti6Al4V titanium alloy tube were conducted to obtain stable heating. The electromagnetic and thermal fields in the process of ultrasonic frequency induction heating were calculated. The effects of the current frequency and current value on the thermal and current fields were numerically analyzed. The increase in current frequency enhances the skin and edge effects, but heat permeability was achieved in the super audio frequency range, and the temperature difference between the interior and exterior of the tube was less than 1%. An increase in the applied current value and current frequency caused an increase in the tube's temperature, but the influence of current was more prominent. Therefore, the influence of stepwise feeding, reciprocating motion, and stepwise feeding superimposed motion on the heating temperature field of the tube blank was evaluated. The coil reciprocating with the roll can maintain the temperature of the tube within the target temperature range during the deformation stage. The simulation results were validated experimentally, which demonstrated good agreement between the results. The numerical simulation method can be used to monitor the temperature distribution of Ti6Al4V alloy tubes during the super-frequency induction heating process. This is an economical and effective tool for predicting the induction heating process of Ti6Al4V alloy tubes. Moreover, online induction heating in the form of reciprocating motion is a feasible strategy for processing Ti6Al4V alloy tubes.

Investigation of the Mechanical Properties and Microstructure of the Co40NiCrMo Alloy Used for STACERs and Prepared by the CSPB Process and the Winding and Stabilization Method.

The Co40NiCrMo alloy, used for STACERs fabricated by the CSPB (compositing stretch and press bending) process (cold forming) and the winding and stabilization (winding and heat treatment) method, was investigated with regard to its tensile property, residual stress, and microstructure. The Co40NiCrMo STACER prepared by the winding and stabilization method was strengthened with lower ductility (tensile strength/elongation: 1562 MPa/5%) compared to that prepared by CSPB (tensile strength/elongation: 1469 MPa/20.4%). The residual stress of the STACER prepared by winding and stabilization (τxy = -137 MPa) showed consistency with that obtained through CSPB (τxy = -131 MPa). Combined with the driving force and pointing accuracy performances, the optimum heat treatment parameters for the winding and stabilization method were determined as 520 °C + 4 h. The HABs in the winding and stabilization STACER (98.3%, of which 69.1% were Σ3 boundaries) were much higher than those in the CSPB STACER (34.6%, of which 19.2% were Σ3 boundaries), while deformation twins and h.c.p ε-platelet networks were present in the CSPB STACER, and many more annealing twins appeared in the winding and stabilization STACER. It was concluded that the strengthening mechanism in the CSPB STACER is the combined action of deformation twins and h.c.p ε-platelet networks, while for the winding and stabilization STACER, annealing twins play the dominant role.

Effective-compound combination of Bufei Yishen formula III combined with ER suppress airway mucus hypersecretion in COPD rats: via EGFR/MAPK signaling.

BACKGROUND: The aim of this study was to explore the combined efficacy ofeffective-component compatibility of Bufei Yishen formula III (ECC-BYF III) and exercise rehabilitation (ER) in inhibiting airway mucus hypersecretion in a chronic obstructive pulmonary disease (COPD) rat model. METHODS: A total of 48 SD rats were divided into control, model, acetylcysteine (NAC), ECC-BYF III, ER, and ECC-BYF III + ER groups (n=8). COPD rats were exposed to cigarette smoke and bacteria for 8 weeks and administered various treatments over the next eight weeks. Rats were euthanized at week 17 after pulmonary function testing. Pathological examination of lung tissues was performed. IL-6 and IL-10 levels were measured in bronchoalveolar lavage fluid (BALF) and protein levels of MUC5AC, MUC5B, AQP-5, EGFR, ERK, JNK, and p38 were measured in lung tissues. RESULTS: Improved pulmonary function and pathological changes were observed in ECC-BYF III, ECC-BYF III + ER, and NAC groups. ECC-BYF III and ECC-BYF III + ER had greater mean alveolar number (MAN) compared with NAC. Lung inflammation and goblet cell generation were reduced and MUC5AC, MUC5B and AQP-5 expressions were lower in all treatment groups. ECC-BYF III has more significant effect on MUC5AC than ER and NAC. ECC-BYFIII + ER had a greater effect on suppressing IL-6 in BALF compared with other treatments. ECC-BYFIII, ER, and ECC-BYF III + ER reduced EGFR, ERK, JNK, and p38 phosphorylated protein levels. ECC-BYFIII+ER had a greater effect on p-JNK and p-p38 than ECC-BYFIII and NAC. CONCLUSION: ECC-BYF III, ER, and ECC-BYF III + ER have efficacy in inhibiting airway mucus hypersecretion with improved pulmonary function and pathological changes. ECC-BYF III had a greater effect in improving MAN and MUC5AC in lung tissue. ECC-BYF III+ER had a greater effect in alleviating pulmonary pathology and inflammation. These effects may be mediated by inhibition of the EGFR/MAPK pathway.

Network Pharmacology and Experimental Validation to Reveal Effects and Mechanisms of Icariin Combined with Nobiletin against Chronic Obstructive Pulmonary Diseases.

Background: Chronic obstructive pulmonary disease (COPD) is a long-term respiratory disorder marked by restricted airflow and persistent respiratory symptoms. According to previous studies, icariin combined with nobiletin (I&N) significantly ameliorates COPD, but the therapeutic mechanisms remain unclear. Purpose: The aim of the study is to investigate the therapeutic mechanisms of I&N against COPD using network pharmacology and experimental validation. Methods: The targets of I&N and related genes of COPD were screened and their intersection was selected. Next, the protein-protein interaction (PPI) networks, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Further, a COPD rat model was established to validate the effect and mechanisms of I&N. Results: 445 potential targets I&N were obtained from SwissTargetPrediction, STITCH 5.0, and PharmMapper databases. 1831 related genes of COPD were obtained from GeneCards, DrugBank, and DisGeNet databases. 189 related genes were screened via matching COPD targets with I&N. 16 highest score targets among 189 targets were obtained according to PPI networks. GO and KEGG pathway enrichment analyses of 16 highest score targets suggested that these key genes of I&N were mostly enriched in the tumor necrosis factor (TNF) pathway, mitogen-activated protein kinase (MAPK) pathway, and phosphatidyl inositol 3-kinase (PI3K)-protein kinase B (AKT) pathway. Therefore, the treatments of I&N for COPD were connected with inflammation-related pathways. In in vivo experiments, the studies indicated that I&N improved the lung function and alleviated the damage of pulmonary histopathology. Moreover, I&N reduced levels of interleukin (IL)-6, IL-1ß, and TNF-α in lung tissues of COPD rats and inhibited the activation of the MAPK pathway and PI3K-Akt pathway. Conclusions: Icariin combined with nobiletin has therapeutic effects on COPD by inhibiting inflammation. The potential mechanisms of I&N may relate to the MAPK pathway and PI3K-Akt pathway.

Poly I:C Exacerbates Airway Inflammation and Remodeling in Cigarette Smoke-Exposed Mice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder characterized by chronic inflammation and airway remodeling. Cigarette smoke (CS) and respiratory viruses are major causes of COPD development and exacerbation, but the mechanisms of these compounding factors on inflammation and pathological changes in airway structure still need further investigation. PURPOSE: This work aimed to investigate the effects and mechanisms of Poly I:C on pathological changes in CS-induced COPD mice, such as airway inflammation and remodeling. METHODS: From 1 to 8 weeks, the mice were exposed to CS, Poly I:C, or a combination of both. To compare the pathological changes among different groups over time, the mice were sacrificed at week 4, 8, 16, and 24, then the lungs were harvested to measure pulmonary pathology, inflammatory cytokines, and airway remodeling. RESULTS: Our data revealed that the fundamental characteristics of COPD, such as pulmonary pathological damage, the release of inflammatory mediators, and the remodeling of airway walls, were observed at week 8 in CS-exposed mice and these pathological changes persisted to week 16. Compared with the CS group, the pathological changes, including decreased lung function, inflammatory cell infiltration, alveolar destruction, and airway wall thickening, were weaker in the Poly I:C group. These pathological changes were observed at week 8 and persisted to week 16 in Poly I:C-induced mice. Furthermore, Poly I:C exacerbated lung tissue damage in CS-induced COPD mice. The decreased lung function, airway inflammation and remodeling were observed in the combined group at week 4, and these pathological changes persisted to week 24. Our research indicated that Poly I:C enhanced the expression of p-P38, p-JNK and p-NF-κB in CS-exposed mice. CONCLUSION: Poly I:C could promote airway inflammation and remodeling in CS-induced COPD mice probably by NF-κB and MAPK signaling.

Metal contamination in soils and windowsill dusts: implication of multiple sources on dust metal accumulation within a city affected by Pb smelting.

The accumulation of total Pb, Cd, Cu, and Zn in soils (0-5 cm) and windowsill dust fractions (45-125, 10-45, and < 10 µm), and soil pollution indices (PI), were investigated in a long-term (~ 70 years) Pb smelter area and in the nearby urban city of Jiyuan, China. Principal component analysis (PCA) was utilized to identify metal contamination sources. Results showed that mean soil Pb, Cd, Cu, and Zn concentrations in the smelter area were 803, 13.8, 118, and 323 mg kg-1, while those of the urban area were 270, 7.95, 51.6, and 244 mg kg-1, respectively. Lead and Cd had greater soil PI than Cu and Zn. Lead concentrations in the 45-125, 10-45, and < 10-µm urban dust fractions ranged from 197.1 to 1953 (mean 1020), 202-3962 (2407), and 51.1-1258 (310.7) mg kg-1, while Cd concentrations ranged from 11.1 to 111 (49.2), 10.4-159 (64.3) and 21.5-131 (60.0) mg kg-1, respectively. Excessive Zn concentrations (5000-22,000 mg kg-1) in some urban dust samples were found at two sampling sites, while Zn concentrations were < 2600 mg kg-1 in all other samples. Based on PCA results, metal accumulation near the Pb smelter was dominated by smelting activities. The PCA results further suggested that mass vehicular transportation modes may be an important source of metals such as Cu and Zn in the urban area. Certain samples in both sub-areas had unsafe potential non-carcinogenic risks of Pb for children. These findings suggest that reducing environmentally relevant metal concentrations in this, and similar areas, will likely require a multi-faceted approach.

Effective Component Compatibility of Bufei Yishen Formula III Which Regulates the Mucus Hypersecretion of COPD Rats via the miR-146a-5p/EGFR/MEK/ERK Pathway.

Background: The effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) with 5 ingredients (ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol) has been shown to protect against chronic obstructive pulmonary disease (COPD). The present study aimed to observe the effects of ECC-BYF III in a COPD rat model and dissect its potential mechanisms in regulating mucus hypersecretion via the miR-146a-5p/epidermal growth factor receptor (EGFR)/MEK/ERK pathway. Methods: COPD model rats were treated with normal saline, ECC-BYF III, or N-acetylcysteine (NAC). Pulmonary function, lung tissue histology with H & E and AB-PAS staining, expression levels of interleukin (IL)-4, IL-6, IL-1ß, MUC5AC, MUC5B, and FOXA2 in lung tissues and the mRNA and proteins involved in the miR-146a-5p/EGFR/MEK/ERK pathway were evaluated. Results: The COPD rats showed a significant decrease in the pulmonary function and serious pathological damage to the lung tissue. ECC-BYF III and NAC significantly improved the ventilation function and small airway pathological damage in the COPD rats. The goblet cells and the expression levels of IL-1ß, IL-6, MUC5AC, and MUC5B were increased in the COPD rats and were significantly decreased after ECC-BYF III or NAC intervention. The expression levels of IL-4 and FOXA2 in the COPD rats were markedly decreased and were improved in the ECC-BYF III and NAC groups. ECC-BYF III appeared to have a potent effect in restoring the reduced expression of miR-146a-5p. The increased phosphorylation levels of EGFR, MEK, and ERK1/2 and the protein expression levels of SPDEF in the lungs of COPD rats could be significantly reduced by ECC-BYF III. Conclusions: ECC-BYF III has a significant effect in improving the airway mucus hypersecretion in COPD model rats, as well as a protective effect against limited pulmonary function and injured lung histopathology. The protective effect of ECC-BYF III in reducing airway mucus hypersecretion in COPD may involve the miR-146a-5p/EGFR/MEK/ERK pathway.