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This study tested the hypothesis that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances polymorphonuclear neutrophils (PMNs) via interleukin (IL)-1β to improve the prognosis of secondary infection in sepsis. The latter stage of sepsis is prone to induce immunosuppression, resulting in secondary fatal infections. Recombinant GM-CSF has become a way for sepsis-induced immunosuppression due to its immunomodulatory effect. However, the functional impact of GM-CSF on PMNs in sepsis remains obscure. This study aimed to study the role of recombinant GM-CSF on the bactericidal ability of PMNs in septic mice, assessing its effect on the prognosis of secondary pneumonia, and explore the mechanism of recombinant GM-CSF by intervening PMNs in patients with sepsis. The C57BL/6J sepsis mouse model was induced by cecal ligation and puncture. Recombinant murine GM-CSF (rmGM-CSF) was used in vivo when mice developed immunosuppression, which was characterized by abnormal bactericidal function of PMNs in peripheral blood. rmGM-CSF improved the prognosis of secondary pneumonia and reversed the function of PMNs. PMNs isolated by Percoll from septic patients were treated by recombinant human GM-CSF (rhGM-CSF) in vitro. The expression of CD11b, reactive oxygen species, phagocytosis, and neutrophil extracellular trap release in PMNs were enhanced by rhGM-CSF treatments. Whole-transcriptomic sequencing of mouse PMNs indicated that recombinant GM-CSF increased the expression of Il1bgene in PMNs. Blocking and inhibiting IL-1β release effectively counteracted the enhancing effect of GM-CSF on the bactericidal function of PMNs. rmGM-CSF enhances the bactericidal function of PMNs in vivo and improves the prognosis of secondary pneumonia in septic mice, and recombinant GM-CSF increases IL-1β precursor reserves, which, if stimulated, can rapidly enhance the bactericidal capacity of PMNs.Pro-IL-1β upraised by recombinant GM-CSF leads to enhanced bactericidal capacity of PMNs and a better outcome of secondary pneumonia in sepsis.

Environmental contextAntibiotic resistance by microorganisms in the natural environment poses a threat to ecosystems and public health. We report findings suggesting kaolinite can effectively inhibit the development of antibiotic resistance genes in microorganisms, and present a new understanding of the molecular mechanisms that promote the development of antibiotic resistance. These results are critical to mitigating environmental and public health risks resulting from the abuse of antibiotics. AbstractAntibiotic resistance and antibiotic resistance genes (ARGs) in the natural environment pose a threat to ecosystems and public health; therefore, better strategies are needed to mitigate the emergence of resistance. This study examined the expression of ARGs in Escherichia coli (E. coli) after exposure to sub-MIC (minimum inhibitory concentration) antibiotics for 15 days in the presence and absence of kaolinite. The results of the real-time polymerase chain reaction (PCR) showed that the expression levels of the eight target genes of E. coli adhering to kaolinite were relatively decreased, and the MIC results also indicated that the final resistance was lower than that of the strains without kaolinite. A close relationship between E. coli and kaolinite was also revealed, as well as a unique interfacial interaction. In addition, the differential protein expression was further analysed to detect proteins and genes associated with ARGs mutations, and then the underlying mechanisms of cell growth and metabolism were identified under low dose ampicillin stress to elucidate the role of kaolinite in the process. Molecular mechanisms analysis determined that when cells adhering to kaolinite were stressed, transport of ampicillin to the periplasmic space was reduced, and the redox metabolism of bacteria was promoted to combat the harsh environment. Moreover, cells synthesised related peptides or proteins under the action of ribosomal proteins to prevent toxic damage. Therefore, this work not only provides new insights into the cellular response to antibiotic stress, but also provides a topic for more research on methods to delay the emergence of ARGs.

Long noncoding RNAs (lncRNAs), defined as the transcripts longer than 200 nt without protein-coding capacity, have been found to be aberrantly expressed in diverse human diseases including leukemia. Our previous study identified Familial acute myelogenous leukemia related factor ( FAMLF) in an acute myeloblastic leukemia (AML) pedigree. Two splice variants of FAMLF, FAMLF-1 and FAMLF-2were detected. FAMLF-1 is upgraded in AML patients and associated with poor prognosis. However, the full cDNA sequence of FAMLF-2is not verified and its role in leukemogenesis remain unclear. Herein, we aim to investigate the functional and mechanistic roles of FAMLF-2in leukemia.

Environmental contextInteractions between microbes and minerals can influence geochemical reactions, and hence are of fundamental importance in natural environmental processes. We investigate the effects of Sphingomonas sp. on the structure and physicochemical properties of montmorillonite, a common clay mineral, and determine how this interaction influences the biodegradation of phenanthrene. The findings have profound impact on the clay-modulated biodegradation of organic compounds in the environment. AbstractWe investigate the effect of Sphingomonas sp. GY2B on the structure and physicochemical properties of montmorillonite (Mt). The simultaneous biodegradation of a polycyclic aromatic hydrocarbon compound, phenanthrene, was also monitored. After interaction with bacteria for 2 days, the increases of the specific surface area (SSA) and micropore volume, differences of the thermogravimetric analysis and differential scanning calorimetry (TGA-DSC) patterns and the morphological changes revealed modification of the physicochemical properties and mineral surface. Although the interlayer spacing of Mt remained unchanged, the appearance and shift of several vibration peaks in the Fourier transform infrared (FTIR) spectra confirmed the structural changes of Mt arising from bacterial activities. Concentrations of the major elements of montmorillonite changed greatly in the aqueous solution, especially Si, Al, Fe and Ca. Based on the analyses of X-ray diffraction (XRD) and FTIR, these changes were mainly ascribed to the formation of precipitates and minerals in the biotic experiment. Changes in the release rate of different elements also substantiated that the GY2B strain has a considerable impact on the dissolution of montmorillonite. Additionally, a preferential release of Si and the 27Al and 29Si cross-polarisation magic-angle spinning nuclear magnetic resonance (CP/MAS NMR) spectra of bacteria-untreated samples demonstrated that tetrahedral sheets were preferentially destroyed and octahedral sheets in montmorillonite were dissolved. These results showed that microorganisms can greatly affect the physical and chemical properties of clay minerals in the clay-modulated biodegradation of hydrophobic organic contaminants. This study provides valuable insight into the clay-modulated microbial remediation of organic pollutants in the environment.