GPS2 ameliorates cigarette smoking-induced pulmonary vascular remodeling by modulating the ras-Raf-ERK axis.

BACKGROUND: Mitogen-activated protein kinase (MAPK)signaling-mediated smoking-associated pulmonary vascular remodeling (PVR) plays an important role in the pathogenesis of group 3 pulmonary hypertension (PH). And G protein pathway suppressor 2 (GPS2) could suppress G-protein signaling such as Ras and MAPK, but its role in cigarette smoking -induced PVR (CS-PVR) is unclear. METHODS: An in vivo model of smoke-exposed rats was constructed to assess the role of GPS2 in smoking-induced PH and PVR. In vitro, the effects of GPS2 overexpression and silencing on the function of human pulmonary arterial smooth cells (HPASMCs) and the underlying mechanisms were explored. RESULTS: GPS2 expression was downregulated in rat pulmonary arteries (PAs) and HPASMCs after CS exposure. More importantly, CS-exposed rats with GPS2 overexpression had lower right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and wall thickness (WT%) than those without. And enhanced proliferation and migration of HPASMCs induced by cigarette smoking extract (CSE) can be evidently inhibited by overexpressed GPS2. Besides, GPS2siRNA significantly enhanced the proliferation, and migration of HPASMCs as well as activated Ras and Raf/ERK signaling, while these effects were inhibited by zoledronic acid (ZOL). In addition, GPS2 promoter methylation level in rat PAs and HPASMCs was increased after CS exposure, and 5-aza-2-deoxycytidine (5-aza) inhibited CSE-induced GPS2 hypermethylation and downregulation in vitro. CONCLUSIONS: GPS2 overexpression could improve the CS-PVR, suggesting that GPS2 might serve as a novel therapeutic target for PH-COPD in the future.

The alterations of oral, airway and intestine microbiota in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Background: Increasing evidence indicates the microbial ecology of chronic obstructive pulmonary disease (COPD) is intricately associated with the disease's status and severity, and distinct microbial ecological variations exist between COPD and healthy control (HC). This systematic review and meta-analysis aimed to summarize microbial diversity indices and taxa relative abundance of oral, airway, and intestine microbiota of different stages of COPD and HC to make comparisons. Methods: A comprehensive systematic literature search was conducted in PubMed, Embase, the Web of Science, and the Cochrane Library databases to identify relevant English articles on the oral, airway, and intestine microbiota in COPD published between 2003 and 8 May 2023. Information on microbial diversity indices and taxa relative abundance of oral, airway, and intestine microbiota was collected for comparison between different stages of COPD and HC. Results: A total of 20 studies were included in this review, involving a total of 337 HC participants, 511 COPD patients, and 154 AECOPD patients. We observed that no significant differences in alpha diversity between the participant groups, but beta diversity was significantly different in half of the included studies. Compared to HC, Prevotella, Streptococcus, Actinomyces, and Veillonella of oral microbiota in SCOPD were reduced at the genus level. Most studies supported that Haemophilus, Lactobacillus, and Pseudomonas were increased, but Veillonella, Prevotella, Actinomyces, Porphyromonas, and Atopobium were decreased at the genus level in the airway microbiota of SCOPD. However, the abundance of Haemophilus, Lactobacillus and Pseudomonas genera exhibited an increase, whereas Actinomyces and Porphyromonas showed a decrease in the airway microbiota of AECOPD compared to HC. And Lachnospira of intestine microbiota in SCOPD was reduced at the genus level. Conclusion: The majority of published research findings supported that COPD exhibited decreased alpha diversity compared to HC. However, our meta-analysis does not confirm it. In order to further investigate the characteristics and mechanisms of microbiome in the oral-airway- intestine axis of COPD patients, larger-scale and more rigorous studies are needed. Systematic review registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42023418726.

A Novel Superhard, Wear-Resistant, and Highly Conductive Cu-MoSi2 Coating Fabricated by High-Speed Laser Cladding Technique.

The pursuit of an advanced functional coating that simultaneously combines high hardness, wear resistance, and superior electrical conductivity has remained an elusive goal in the field of copper alloy surface enhancement. Traditional solid solution alloying methods often lead to a significant increase in electron scattering, resulting in a notable reduction in electrical conductivity, making it challenging to achieve a balance between high hardness, wear resistance, and high conductivity. The key lies in identifying a suitable microstructure where dislocation motion is effectively hindered while minimizing the scattering of conductive electrons. In this study, a novel Cu-MoSi2 coating was successfully fabricated on a CuCrZr alloy surface using the coaxial powder feeding high-speed laser cladding technique, with the addition of 10-30% MoSi2 particles. The coating significantly enhances the hardness and wear resistance of the copper substrate while maintaining favorable electrical conductivity. As the quantity of MoSi2 particles increases, the coating's hardness and wear resistance gradually improve, with minimal variance in conductivity. Among the coatings, the Cu-30%MoSi2 coating stands out with the highest hardness (974.5 HV0.5) and the lowest wear amount (0.062 mg/km), approximately 15 times the hardness of the copper base material (65 HV0.5) and only 0.45% of the wear amount (13.71 mg/km). Additionally, the coating exhibits a resistivity of 0.173 × 10-6 Ω·m. The extraordinary hardness and wear resistance of these coatings can be attributed to the dispersion strengthening effect of MoxSiy particles, while the high electrical conductivity is due to the low silicon content dissolved into the copper from the released MoSi2 particles, as well as the rapid cooling rates associated with the high-speed laser cladding process.