Difluoromethylated Difunctionalization of Alkenes under Visible Light.

Difluoromethylated compounds usually act as bioisosteres for alcohol functional groups and show unique physicochemical and biological properties. The cyano-difluoromethylation of alkenes using 5-((difluoromethyl)sulfonyl)-1-phenyl-1H-tetrazole as a CF2H radical difluoromethyl precursor was developed to afford nitriles including a CF2H group. A low-cost, stable, easily handled 5-((difluoromethyl)sulfonyl)-1-methyl-1H-tetrazole (DFSMT) was synthesized and applied as the radical CF2H reagent. Using DFSMT as the radical CF2H precursor, the oxyl-difluoromethylation of alkenes was developed to obtain difluoromethylated ether products. All of the reactions showed good functional group tolerability. Initial mechanistic experiments indicated that the CF2H radical was involved as the key active intermediate.

Pollinator Proboscis Length Plays a Key Role in Floral Integration of Honeysuckle Flowers (Lonicera spp.).

Pollinator-mediated selection is supposed to influence floral integration. However, the potential pathway through which pollinators drive floral integration needs further investigations. We propose that pollinator proboscis length may play a key role in the evolution of floral integration. We first assessed the divergence of floral traits in 11 Lonicera species. Further, we detected the influence of pollinator proboscis length and eight floral traits on floral integration. We then used phylogenetic structural equation models (PSEMs) to illustrate the pathway through which pollinators drive the divergence of floral integration. Results of PCA indicated that species significantly differed in floral traits. Floral integration increased along with corolla tube length, stigma height, lip length, and the main pollinators' proboscis length. PSEMs revealed a potential pathway by which pollinator proboscis length directly selected on corolla tube length and stigma height, while lip length co-varied with stigma height. Compared to species with short corolla tubes, long-tube flowers may experience more intense pollinator-mediated selection due to more specialized pollination systems and thus reduce variation in the floral traits. Along elongation of corolla tube and stigma height, the covariation of other relevant traits might help to maintain pollination success. The direct and indirect pollinator-mediation selection collectively enhances floral integration.

Neutrophils inhibit CD8+ T cells immune response by arginase-1 signaling in patients with sepsis.

BACKGROUND: Patients with sepsis often exhibit an acute inflammatory response, followed by an immunosuppressive phase with a poor immune response. However, the underlying mechanisms have not been fully elucidated. METHODS: We sought to comprehensively characterize the transcriptional changes in neutrophils of patients with sepsis by transcriptome sequencing. Additionally, we conducted a series of experiments, including real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry to investigate the role of arginase-1 signaling in sepsis. RESULTS: Through the analysis of gene expression profiles, we identified that the negative regulation of T cell activation signaling was enriched, and the expression of arginase-1 was high in neutrophils from patients with sepsis. Furthermore, we conducted flow cytometry and found that the function of CD8+ T cells in septic patients was impaired. Moreover, neutrophils from septic patients inhibited the percentage of polyfunctional effector CD8+ T cells through arginase-1. Additionally, the proportions of granzyme B+IFN-γ+CD8+ T and TNF-α+IFN-γ+CD8+ T cells increased after inhibition of arginase-1 signaling. CONCLUSION: The impaired effector function of CD8+ T cells could be restored by blocking arginase-1 signaling in patients with sepsis.

Effects of prehospital management in out-of-hospital cardiac arrest: advanced airway and adrenaline administration.

BACKGROUND: There is uncertainty about the best approaches for advanced airway management (AAM) and the effectiveness of adrenaline treatments in Out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate whether AAM and adrenaline administration provided by Emergency Medical Service (EMS) can improve the outcomes of OHCA. METHODS: This study was a prospective analysis of collected data based on OHCA adult patients treated by the EMS in China from January 2019 to December 2020.The patients were divided into AAM group and no AAM group, and into subgroups according to whether adrenaline was used. The outcome was rate of return of spontaneous circulation (ROSC), survival to admission and hospital discharge. RESULTS: 1533 OHCA patients were reported. The probability of ROSC outcome and survival admission in the AAM group was significantly higher, compared with no AAM group. The probability of ROSC outcome in the AAM group increased by 66% (adjusted OR: 1.66, 95%CI, 1.02-2.71). There were no significant differences in outcomes between the adrenaline and no adrenaline groups. The combined treatment of AAM and adrenaline increased the probability of ROSC outcome by 114% (adjusted OR, 2.14, 95%CI, 1.20-3.81) and the probability of survival to admission increased by 115% (adjusted OR, 2.15, 95%CI, 1.16-3.97). CONCLUSIONS: The prehospital AAM and the combined treatment of AAM and adrenaline in OHCA patients are both associated with an increased rate of ROSC. The combined treatment of AAM and adrenaline can improve rate of survival to admission in OHCA patients.