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Pasteurella multocida (P. multocida) can cause infection in various animals, especially livestock and poultry, which can lead to substantial losses to the breeding industry. However, the pathogenesis of avian P. multocida remains largely unknown. In this study, the mechanisms of avian P. multocida pathogenesis were explored. Chicken macrophage HD11 cells were infected with the avian strain PmQ and the bovine strain PmCQ2. PmQ induced higher cytotoxicity and apoptosis and exerted a stronger anti-phagocytotic effect on HD11 cells than PmCQ2. RNA sequencing analysis revealed that focal adhesion (FA)-related genes were significantly downregulated in PmQ-infected HD11 cells compared with that of PmCQ2. Subsequently, phalloidin staining of the F-actin assembly revealed that PmQ more significantly inhibited the formation of FAs in HD11 than PmCQ2. Western blot analysis revealed that the levels of Zyxin and phosphorylated focal adhesion kinase (FAK) were significantly decreased in PmQ-infected cells, confirming that PmQ inhibited FAs. Consequently, PmQ inhibited the FA downstream factor Akt, which decreased NF-κB and FoxO1 phosphorylation, as evidenced by the decreased expression of downstream anti-apoptotic genes (GADD45B, BCL2L1, BCL2A1, and BIRC2) and increased expression of downstream pro-apoptotic genes (BCL6, PKL2, PKL3, and KLF2). Conversely, pharmaceutically inhibiting FA formation using latrunculin A better enhanced PmCQ2-induced than PmQ-induced apoptosis in HD11 cells. Similarly, the knockdown of Zyxin or FoxO1 by siRNA both boosted the PmCQ2-induced apoptosis rates equal to those of PmQ. These results demonstrated that PmQ inhibited Zyxin-dependent FA formation and disrupted the FAK-AKT-FoxO1/NF-κB pathway to induce apoptosis in chicken macrophages. This study thus offers insights into the pathogenesis of avian P. multocida, which could facilitate the development of new strategies against P. multocida infection.

Abstract Pasteurella multocida is an opportunistic zoonotic pathogen that primarily causes fatal respiratory diseases, such as pneumonia and respiratory syndromes. However, the precise mechanistic understanding of how P. multocida disrupts the epithelial barrier in mammalian lung remains largely unknown. In this study, using unbiased RNA-seq analysis, we found that the evolutionarily conserved Hippo-Yap pathway was dysregulated after P. multocida infection. Given the complexity of P. multocida infection associated with lung injury and systemic inflammatory processes, we employed a combination of cell culture models, mouse models, and rabbit models to investigate the dynamics of the Hippo-Yap pathway during P. multocida infection. Our findings reveal that P. multocida infection activates the Hippo-Yap pathway both in vitro and in vivo, by upregulating the upstream factors p-Mst1/2, p-Lats1, and p-Yap, and downregulating the downstream effectors Birc5, Cyr61, and Slug. Conversely, pharmacological inhibition of the Hippo pathway by XMU-MP-1 significantly rescued pulmonary epithelial cell apoptosis in vitro and reduced lung injury, systemic inflammation, and mouse mortality in vivo. Mechanistic studies revealed that P. multocida induced up-regulation of Rassf1 expression, and Rassf1 enhanced Hippo-Yap pathway through phosphorylation. Accordingly, in vitro knockdown of Rassf1 significantly enhanced Yap activity and expression of Yap downstream factors and reduced apoptosis during P. multocida infection. P. multocida-infected rabbit samples also showed overexpression of Rassf1, p-Lats1, and p-Yap, suggesting that P. multocida activates the Rassf1-Hippo-Yap pathway. These results elucidate the pathogenic role of the Rassf1-Hippo-Yap pathway in P. multocida infection and suggest that this pathway has the potential to be a drug target for the treatment of pasteurellosis.

Abstract Crystalline porous materials such as covalent organic frameworks (COFs), metal-organic frameworks (MOFs) and porous organic cages (POCs) have been widely applied in various fields with outstanding performances. However, the lack of general and effective methodology for large-scale production limits their further industrial applications. In this work, we developed a general approach comprising high pressure homogenization (HPH), which can realize large-scale synthesis of crystalline porous materials including COFs, MOFs, and POCs under benign conditions. This universal strategy, as illustrated in the proof of principle studies, has prepared 4 COFs, 4 MOFs, and 2 POCs. It can circumvent some drawbacks of existing approaches including low yield, high energy consumption, low efficiency, weak mass/thermal transfer, tedious procedures, poor reproducibility, and high cost. On the basis of this approach, an industrial homogenizer can produce 0.96 ~ 580.48 ton of high-performance COFs, MOFs, and POCs per day, which is unachievable via other methods.

The performance of adsorbents for perfluorooctanoic acid (PFOA) removal often suffers from long equilibrium times, weak binding affinities and poor stability. Here the authors report a highly efficient PFOA adsorbents by functionalizing porous organic polymers with electrostatic and hydrophobic binding sites.

Abstract Coordination polymers (CPs), as emerging crystalline porous materials, have exhibited intriguing and promising performance in energy applications for various ion transports including proton, hydroxide, and alkali metal ions. Their advantageous features of high designabilities, stabilities, tunable pore sizes, and adjustable functional sites are beneficial for ion transports. More importantly, these features also exhibit important merits for adjusting ion concentration and enhancing the mobility of carriers in practical applications. To further explore the relationship between chemical structures and transport behaviors, we present an overview of the advancements of CPs as ion conductors in the past two decades in terms of dimensionalities. In this review, we would also discuss the fundamental strategies for enhancing energy ion transfer performance. Furthermore, the challenging issues and future prospects in this area would be also elaborated.

Hedychium puerense, a perennial rhizomatous herb, is used as an ornamental, medicinal, and edible plant in Yunnan Province, China. Essential oils from Hedychium plants are widely used in perfumes and traditional medicine, but there are no studies on the constituents and bioactivities of H. puerense essential oil (EO). Therefore, this study was designed to explore the chemical composition, antibacterial, enzyme-inhibitory, and anti-inflammatory activities of H. puerense rhizome EO. The gas chromatography with flame ionization or mass selective detection (GC-FID/MS) results indicated that H. puerense EO was mainly composed of linalool (26.5%), β-pinene (18.6%), γ-terpinene (12.1%), terpinen-4-ol (7.7%), α-pinene (5.8%), sabinene (4.9%), E-nerolidol (4.1%), and p-cymene (3.6%). For biological activities, H. puerense EO displayed broad-spectrum antibacterial properties against Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, and Escherichia coli with diameter of inhibition zone (DIZ) values ranging from 7.44 to 10.30 mm, a minimal inhibitory concentration (MIC) of 3.13–6.25 mg/m), and a minimal bactericidal concentration (MBC) of 3.13–12.50 mg/mL. Moreover, the EO significantly inhibited acetylcholinesterase (AChE) (IC50 = 0.94 ± 0.02 mg/mL) and butyrylcholinesterase (BChE) (IC50 = 1.32 ± 0.06 mg/mL) activities, and exhibited a moderate inhibitory effect on α-glucosidase (IC50 = 5.42 ± 0.32 mg/mL) and tyrosinase (IC50 = 3.23 ± 0.21 mg/mL). Furthermore, the EO significantly suppressed the secretion of the pro-inflammatory mediator, nitric oxide (NO) (99.23 ± 0.26%), cytokines tumor necrosis factor-α (TNF-α) (97.14 ± 0.11%), and interleukin-6 (IL-6) (82.42 ± 0.16%) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at 250 μg/mL without cytotoxicity. Hence, H. puerense EO can be considered a bioactive, natural product that has great potential for utilization in the fields of food, cosmetics, and pharmaceutics.

The chemical composition and biological activities of the essential oil from Ficus tikoua Bur. were reported for the first time. Fifty-three compounds, accounting for 99.60% of the total essential oil composition, were identified and the main components were palmitic acid (51.13%) and linoleic acid (47.54%). The essential oil revealed significant antibacterial activity with the inhibition zones (7.89-10.59 mm), MIC (0.20-6.25 mg/mL) and MBC (0.20-12.50 mg/mL) against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris. The essential oil exhibited significant cytotoxicity against A549, NCI-H1299, PC-3 and K562 tumor cells with the IC50 values of 131.08, 50.32, 120.58 and 31.68 µg/mL, respectively. The essential oil exhibited selective cytotoxic activity to human tumor cell lines, with a significantly lower cytotoxicity to human normal cell line (MRC-5, IC50 = 161.75 µg/mL) than to tumor cells. Additionally, palmitic acid, as the major compound, aslo revealed significant antibacterial and cytotoxic activities. [ABSTRACT FROM AUTHOR]