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Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling. [Display omitted] • Inhaled particular matter induced airway smooth muscle remodeling. • PM2.5 led to ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP). • SASP contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. • Inhibition of SASP prevented PM2.5-induced airway remodeling. [ABSTRACT FROM AUTHOR]

Clamping precision as a key factor of precision injection molding of high-quality plastic parts is restricted by low-precision clamping systems. Herein, a novel clamping method capable of sensing mold misalignment and self-adjusting mold position and attitude through floating structures is proposed to eliminate the restriction of clamping system, thereby achieving high clamping precision. The innovative clamping method possesses prestress steel wire-winding frames and rubber capsules filled with hydraulic oil, which ensures the floating structures work. Meanwhile, the hydraulic oil provides isostatic pressure to clamp the mold. The working space of the floating structures and the loading of the prestress steel wire-winding frames have been modeled to confirm their feasibility in the self-adaptive clamping method. Based on the modeling activities, a prototype injection molding machine was developed to evaluate the clamping precision. The experimental results indicate that the parallelism between the mold plates is 0.031 mm, far superior to that in China Machinery Industry Standards, and the uneven clamping force rate on mold cavity surface is 1.3 %. Moreover, the clamping force repeatability is only 0.14 %, superior to toggle and two-platen clamping systems. This method offers a new chance for the development of precision injection molding. • A novel clamping method capable of sensing mold misalignment and self-adjusting mold position and attitude. • The clamping method utilizes capsule with hydraulic oil to provide isostatic pressure and ensure floating structures work. • The prestress steel wire-winding frames in the clamping system cannot restrict degree of freedom of floating structures. • The developed clamping system is verified that the clamping precision is superior to traditional clamping systems. [ABSTRACT FROM AUTHOR]

Monopolar spindle 1 (MPS1) has garnered significant attention due to its pivotal role in regulating the cell cycle. Anomalous expression and hyperactivation of MPS1 have been associated with the onset and advancement of diverse cancers, positioning it as a promising target for therapeutic interventions. This review focuses on MPS1 small molecule inhibitors from the past decade, exploring design strategies, structure-activity relationships (SAR), safety considerations, and clinical performance. Notably, we propose prospects for MPS1 degraders based on proteolysis targeting chimeras (PROTACs), as well as reversible covalent bonding as innovative MPS1 inhibitor design strategies. The objective is to provide valuable information for future development and novel perspectives on potential MPS1 inhibitors. [Display omitted] • This review encapsulates a decade of MPS1 inhibitor advancements, drawing on patent literature insights. • Focuses on design strategies, structure-activity relationships, safety protocols, and clinical outcomes of MPS1 inhibitors. • Foresees advancements in MPS1 degradation via proteolysis targeting chimeras (PROTACs) and reversible covalent inhibitors. [ABSTRACT FROM AUTHOR]

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. The NGPV, a single-stranded DNA virus, is thought to be vertically transmitted. However, the mechanism of NGPV immune evasion remains unclear. In this study, we investigated the impact of NGPV infection on the Cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway in duck embryonic fibroblast (DEF) cells. Our findings demonstrate that NGPV infection stimulates the mRNA expression of cGAS but results in weak IFN-β induction. NGPV impedes the expression of IFN-β and downstream interferon-stimulated genes, thereby reducing the secretion of IFN-β induced by interferon-stimulating DNA (ISD) and poly (I: C). RNA-seq results show that NGPV infection downregulates interferon mRNA expression while enhancing the mRNA expression of inflammatory factors. Additionally, the results of viral protein over-expression indicate that VP1 exhibits a remarkable ability to inhibit IFN-β expression compared to other viral proteins. Results indicated that only the intact VP1 protein could inhibit the expression of IFN-β, while the truncated proteins VP1U and VP2 do not possess such characteristics. The immunoprecipitation experiment showed that both VP1 and VP2 could interact with IRF7 protein, while VP1U does not. In summary, our findings indicate that NGPV infection impairs the host's innate immune response by potentially modulating the expression and secretion of interferons and interferon-stimulating factors via IRF7 molecules, which are regulated by the VP1 protein. [ABSTRACT FROM AUTHOR]

The mitochondrial quality control system is crucial in maintaining cellular homeostasis during environmental stress. Granulosa cells are the main cells secreting steroid hormones, and mitochondria are the key organelles for steroid hormone synthesis. The impact of the mitochondrial quality control system on granulosa cells' steroid hormone synthesis and survival under heat stress is still unclear. Here, we showed that acute heat stress induces mitochondrial damage and significantly increases the number of mitophagy-like vesicles in the cytoplasm of duck ovary granulosa cells at the ultra-structural level. Meanwhile, we also found heat stress significantly increased mitochondrial fission and mitophagy-related protein expression levels both in vivo and in vitro. Furthermore, by confocal fluorescence analysis, we discovered that LC3 was distributed spot-like manner near the nucleus in the heat treatment group, and the LC3 spots and lysosomes were colocalized with Mito-Tracker in the heat treatment group. We further detected the mitophagy-related protein in the cytoplasm and mitochondria, respectively. Results showed that the PINK1 protein was significantly increased both in cytoplasm and mitochondria, while the LC3-Ⅱ/LC3-Ⅰ ratio increase only occurred in mitochondrial. In addition, the autophagy protein induced by acute heat treatment was effectively inhibited by the mitophagy inhibitor CysA. Finally, we demonstrated that the alteration of cellular mitophagy by siRNA interference with Drp1 and PINK1 inhibited the steroid synthesis of granulosa cells and increased cell apoptosis. Study provides strong evidence that the Drp1 regulated PINK1-dependent mitophagy pathway protects follicular granulosa cells from acute heat stress-induced injury. [ABSTRACT FROM AUTHOR]