应对可转移多黏菌素耐药性--饲料添加剂来源的白屈菜红碱具有双重效应

The emergence and spread of the mobile colistin-resistance gene,mcr-1,and its variants pose achallenge to the use of colistin,a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant(XDR)Gram-negative pathogens.Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens;however,few studies have considered the effects of adjuvants on limiting resistance-gene transmission.We found that chelerythrine(4 mg·L^(-1))derived from Macleaya cordata extract,which is used as an animal feed additive,reduced the minimal inhibitory concentration(MIC)of colistin against an mcr-1 positive Escherichia coli(E.coli)strain by 16-fold(from 2.000 to 0.125 mg·L^(-1)).eliminated approximately 10^(4) colony-forming units(CFUs)of an mcr-1-carrying strain in a murine intestinal infection model,and inhibited the conjugation of an mcr-1-bearing plasmid in vitro(by>100-fold)and in a mouse model(by up to 5-fold).A detailed analysis revealed that chelery-thrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity,thereby impairing respiration,disrupting proton motive force(PMF),generating reactive oxygen species(ROS),and decreasing intracellular adenosine triphosphate(ATP)levels,which subsequently downregu-lates mcr-1 and conjugation-associated genes.These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.

Innovation for forming aluminum alloy thin shells at ultra-low temperature by the dual enhancement effect

Integral thin shells made of high strength aluminum alloys are urgently needed in new generation transportation equipment. There are challenges to overcoming the co-existing problems of wrinkling and splitting by the cold forming and hot forming processes. An innovative technology of ultra-low temperature forming has been invented for aluminum alloy thin shells by the new phenomenon of ‘dual enhancement effect’. That means plasticity and hardening are enhanced simultaneously at ultra-low temperatures. In this perspective, the dual enhancement effect is described, and the development, current state and prospects of this new forming method are introduced. This innovative method can provide a new approach for integral aluminum alloy components with large size, ultra-thin thickness, and high strength. An integral tank dome of rocket with 2 m in diameter was formed by using a blank sheet with the same thickness as the final component, breaking through the limit value of thickness-diameter ratio.

Influence of Wind Turbine Structural Parameters on Wind Shear and Tower Shadow Effect

To overcome the problems of natural decreases in power quality,and to eliminate wind speed fluctuation due to wind shear and tower shadow effect arising from wind turbine structural parameters,an improved prediction model accounting for the dual effect of wind shear and tower shadow is,in this paper,built.Compared to the conventional prediction model,the proposed model contains a new constraint condition,which makes the disturbance term caused by the tower shadow effect always negative so that the prediction result is closer to the actual situation.Furthermore,wind turbine structural parameters such as hub height,rotor diameter,the diameter of the tower top,and rotor overhang on wind shear and tower shadow effect are also explored in detail.The results show that the wind shear effect became weaker with the increase in hub height.The hub height is independent of the tower shadow effect.The rotor diameter is positively correlated with the wind shear and tower shadow effect.The tower shadow effect is positively correlated with the diameter of the tower top and negatively correlated with the rotor overhang.

Nanotherapeutics targeting autophagy regulation for improved cancer therapy

The clinical efficacy of current cancer therapies falls short,and there is a pressing demand to integrate new targets with conventional therapies.Autophagy,a highly conserved self-degradation process,has received considerable attention as an emerging therapeutic target for cancer.With the rapid development of nanomedicine,nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance.Hence,considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy,we outline the latest advances in autophagy-based nanotherapeutics.Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression,the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated.Further,emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways,including modulation of the mammalian target of rapamycin(mTOR)pathway,autophagy-related(ATG)and its complex expression,reactive oxygen species(ROS)and mitophagy,interference with autophagosome-lysosome fusion,and inhibition of hypoxia-mediated autophagy.In addition,combination therapies in which nano-autophagy modulation is combined with chemotherapy,phototherapy,and immunotherapy are also described.Finally,the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.

Understanding the attributes of the dual oasis effect in an arid region using remote sensing and observational data

Investigating the attributes of the dual oasis effect and oasis–desert interactions is crucial for understanding the climatic and ecological effects of oases.In this study,oasis effect intensity(OEI)was used as an indicator to investigate the factors that contribute to the dual oasis effect.The oasis effect has two attributes:the surface oasis heating effect(OHE)occurred in winter,while the oasis cooling effect(OCE)occurred in the other three seasons,especially in summer.During the day,the OEI of the whole oasis was−12.8℃,−5.2℃,and−4.5℃ in summer,spring,and autumn,respectively,which indicated a strong OCE;and OEI was 0.5℃ in winter,which indicated a weaker OHE.In arid regions,the OCE dominated most of the time,but the OHE occurred in winter and cannot be ignored.In addition,through statistical analysis and energy balance analysis,high evapotranspiration of the oasis was the main factor leading to the occurrence of OCE in the summer,while low albedo to the occurrence of OHE in winter.