Pasteurella multocida activates apoptosis via the FAK-AKT-FOXO1 axis to cause pulmonary integrity loss, bacteremia, and eventually a cytokine storm.

Pasteurella multocida is an important zoonotic respiratory pathogen capable of infecting a diverse range of hosts, including humans, farm animals, and wild animals. However, the precise mechanisms by which P. multocida compromises the pulmonary integrity of mammals and subsequently induces systemic infection remain largely unexplored. In this study, based on mouse and rabbit models, we found that P. multocida causes not only lung damage but also bacteremia due to the loss of lung integrity. Furthermore, we demonstrated that bacteremia is an important aspect of P. multocida pathogenesis, as evidenced by the observed multiorgan damage and systemic inflammation, and ultimately found that this systemic infection leads to a cytokine storm that can be mitigated by IL-6-neutralizing antibodies. As a result, we divided the pathogenesis of P. multocida into two phases: the pulmonary infection phase and the systemic infection phase. Based on unbiased RNA-seq data, we discovered that P. multocida-induced apoptosis leads to the loss of pulmonary epithelial integrity. These findings have been validated in both TC-1 murine lung epithelial cells and the lungs of model mice. Conversely, the administration of Ac-DEVD-CHO, an apoptosis inhibitor, effectively restored pulmonary epithelial integrity, significantly mitigated lung damage, inhibited bacteremia, attenuated the cytokine storm, and reduced mortality in mouse models. At the molecular level, we demonstrated that the FAK-AKT-FOXO1 axis is involved in P. multocida-induced lung epithelial cell apoptosis in both cells and animals. Thus, our research provides crucial information with regard to the pathogenesis of P. multocida as well as potential treatment options for this and other respiratory bacterial diseases.

Pasteurella multocida activates Rassf1-Hippo-Yap pathway to induce pulmonary epithelial apoptosis.

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.

Transcriptomic Analysis Reveals the Potential Mechanisms for Improving Carotenoid Production in Rhodosporidium toruloides Z11 under Light Stress.

Carotenoids, as a type of tetraterpene compound, have been widely used in food, medical, and health areas owing to their antioxidant, immune enhancement, and disease risk reduction effects. Rhodosporidium toruloides is a promising oleaginous red yeast that can industrially synthesize carotenoids. In this study, the effects of different light exposure times and intervals on carotenoid production by R. toruloides Z11 were first investigated. Results showed that a higher carotenoid content (1.29 mg/g) can be achieved when R. toruloides Z11 was exposed to light for 12 h per day, which was increased by 1.98 times compared with that of dark cultivation. Transcriptome profiling revealed that light stress could effectively promote the gene expression levels of GGPS1 and AL1 in the carotenoid biosynthesis pathway and phr in the DNA photolysis pathway of R. toruloides. This work will provide a molecular foundation to further improve the production efficiency of carotenoids by genetic engineering.

Emergence and genomic analysis of a novel sublineage of bovine ephemeral fever virus in Southwest China.

Introduction: Bovine ephemeral fever virus (BEFV), belonging to the genus Ephemerovirus under the family Rhabdoviridae, is the etiological cause for the bovine ephemeral fever (BEF) in cattle and water buffalo. Methods: In this study, we report recent BEF outbreaks in Southwest China and sequence the complete genome sequence of one BEFV isolate BEFV/CQ1/2022. Results and Discussion: Comparative genomic analyses between BEFV/CQ1/2022 and isolates available in GenBank revealed remarkable inter-isolate divergence. Meanwhile, the sequence divergence was related to the evolutionary relationships and geographical distribution of the isolates. Phylogenetic analysis indicated that the global BEFV isolates can be divided into 4 distinct lineages. The East Asia lineage was the most diverse and could be subdivided into 4 sublineages. Notably, BEFV/CQ1/2022 and other 10 recent isolates from Mainland China were found to be clustered in sublineage 2. Additionally, recombination analysis provided evidence of BEFV recombination among East Asian isolates for the first time. Taken together, a novel sublineage of the East Asian BEFV emerged in Southwest China, and large divergence and potential recombination among BEFV strains were investigated in this study, which may improve understanding of BEFV epidemiology and evolution.

Carotenoids production and genome analysis of a novel carotenoid producing Rhodococcus aetherivorans N1.

Carotenoids are a series of natural pigments with unique structure and physiological functions. In this study, a novel Rhodococcus aetherivorans strain N1 was discovered, which can produce 6.4 mg/g carotenoids including ß-carotene, zeaxanthin and isorenieratene from glucose. Moreover, strain N1 can directly produce 3.0 mg/g carotenoids from the undetoxified straw hydrolysate, representing the highest carotenoids production from the undetoxified lignocellulosic hydrolysate. The crude carotenoid extracts of strain N1 showed efficient free radical scavenging activity and stability. Strain N1 has complete methylerythritol 4-phosphate (MEP) pathway and related genes for carotenoid synthesis, especially the rare aromatic carotenoid of isorenieratene. Genomic comparison between strain N1 and other carotenoid producing Rhodococcus sp. strains showed the conservatism and universality of carotenoids synthesis gene. These results proved that R. aetherivorans strain N1 can serve as a promising producer for the industrialization of carotenoid production.

RAA Enzyme Is a New Family of Class A Extended-Spectrum ß-Lactamase from Riemerella anatipestifer Strain RCAD0122.

Whole-genome sequencing of Riemerella anatipestifer isolate RCAD0122 revealed a chromosomally located ß-lactamase gene, blaRAA-1, which encoded a novel class A extended-spectrum ß-lactamase (ESBL), RAA-1. RAA-1 shared ≤65% amino acid sequence identity with other characterized ß-lactamases. The kinetic assay of native purified RAA-1 revealed ESBL-like hydrolysis activity. Furthermore, blaRAA-1 could be transferred to a homologous strain by natural transformation. However, an epidemiological study showed that the blaRAA-1 gene is not prevalent currently.

Challenges and Future Perspectives of Promising Biotechnologies for Lignocellulosic Biorefinery.

Lignocellulose is a kind of renewable bioresource containing abundant polysaccharides, which can be used for biochemicals and biofuels production. However, the complex structure hinders the final efficiency of lignocellulosic biorefinery. This review comprehensively summarizes the hydrolases and typical microorganisms for lignocellulosic degradation. Moreover, the commonly used bioprocesses for lignocellulosic biorefinery are also discussed, including separated hydrolysis and fermentation, simultaneous saccharification and fermentation and consolidated bioprocessing. Among these methods, construction of microbial co-culturing systems via consolidated bioprocessing is regarded as a potential strategy to efficiently produce biochemicals and biofuels, providing theoretical direction for constructing efficient and stable biorefinery process system in the future.

Introducing Trifluoromethyl to Strengthen Hydrogen Bond for High Efficiency Organic Solar Cells.

Nowadays, the ternary strategy has become a common way to improve the power conversion efficiency (PCE) of organic solar cells (OSCs). The intermolecular interaction between the third component and donor or acceptor plays a key role in achieving a high performance. However, hydrogen bond as a strong intermolecular interaction is rarely considered in ternary OSCs. In this work, we introduce trifluoromethyl on a newly synthesized small molecular DTBO to strength hydrogen bonds between DTBO and IEICO-4F. Due to the existence of hydrogen bonds has a strong impact on electrostatic potential (ESP) and benefits π-π stacking in the active layer, the ternary OSCs show superior charge extraction and low charge recombination. In DTBO, PTB7-Th and IEICO-4F based ternary devices, the PCE increases from 11.02 to 12.48%, and short-circuit current density (J SC ) increases from 24.94 to 26.43 mA/cm2 compared with typical binary devices. Moreover, the addition of DTBO can realize an energy transfer from DTBO to PTB7-Th and broaden the absorption spectrum of blend films. Grazing-incidence wide-angle X-ray scattering (GIWAXS) patterns show that the π-π stacking distance of IEICO-4F decreased after adding 10 wt% DTBO. The effect of the hydrogen bond is also achieved in the PM6: Y6 system, showing 16.64% efficiency by comparison to the 15.49% efficiency of binary system. This work demonstrates that introduce trifluoromethyl to enhance hydrogen bond which improve π-π stacking can achieve higher performance in OSCs.