Light-up luminescence sensors have been employed in real-time in situ visual detection of target molecules including volatile organic compounds (VOCs). However, currently employed light-up sensors, which are generally based on the aggregation-induced emission (AIE) or solvent-induced energy transfer effect, exhibit limited sensitivity for light-up detection and poor recycling performances thereby significantly hindering their industrial applications. Inspired by the low-temperature enhanced luminescence phenomenon, we herein propose and show that a guest-lock-induced luminescence enhancement mechanism can be used to realize the ultrafast light-up detection of target VOCs. Through introduction of chlorinated hydrocarbons to lock the molecular vibrations within a designed [Cu 4 I 4 ]-based metal−organic framework (MOF), luminescence intensity could be enhanced significantly at room temperature. This guest-lockinduced luminescence enhancement is brought about by weak supramolecular interactions between the host framework and the guest molecules, allowing highly sensitive and specific detection of the guest vapor with ultrafast response time (<1 s). Single-crystal X-ray diffraction (SCXRD) analysis of guest molecules-loaded MOFs and density functional theory (DFT) calculations were employed to investigate the host−guest interactions involved in this phenomenon. Moreover, the above MOF sensor successfully achieved real-time detection of a toxic chloroaromatic molecule, chlorobenzene. The guest-lock-induced light-up mechanism opens up a route to discovering high-performance ultrafast light-up luminescent sensors for real-time detection applications.
Methicillin-resistant Staphylococcus aureus (MRSA), are the most frequent cause of sepsis, which urgently demanding new drugs for treating infection. Two homologous insect CSαβ peptides-DLP2 and DLP4 from Hermetia illucens were firstly expressed in Pichia pastoris, with the yields of 873.5 and 801.3 mg/l, respectively. DLP2 and DLP4 displayed potent antimicrobial activity against Gram-positive bacteria especially MRSA and had greater potency, faster killing, and a longer postantibiotic effect than vancomycin. A 30-d serial passage of MRSA in the presence of DLP2/DLP4 failed to produce resistant mutants. Macromolecular synthesis showed that DLP2/DLP4 inhibited multi-macromolecular synthesis especially for RNA. Flow cytometry and electron microscopy results showed that the cell cycle was arrested at R-phase; the cytoplasmic membrane and cell wall were broken by DLP2/DLP4; mesosome-like structures were observed in MRSA. At the doses of 3‒7.5 mg/kg DLP2 or DLP4, the survival of mice challenged with MRSA were 80‒100%. DLP2 and DLP4 reduced the bacterial translocation burden over 95% in spleen and kidneys; reduced serum pro-inflammatory cytokines levels; promoted anti-inflammatory cytokines levels; and ameliorated lung and spleen injury. These data suggest that DLP2 and DLP4 may be excellent candidates for novel antimicrobial peptides against staphylococcal infections.
NAC (NAM, ATAF, and CUC) transcription factors are important regulator in abiotic stress and plant development. However, knowledge concerning the functions of plant NAC TFs functioning in stress tolerance and the underlying molecular basis are still limited. In this study, we report functional characterization of the NAC TF, PbeNAC1, isolated from Pyrus betulifolia. PbeNAC1 were greatly induced by cold and drought, while salt stress had little effect on expression. PbeNAC1 was localized in the nuclei showed transactivation activity. Overexpression of PbeNAC1 conferred enhanced tolerance to multiple stresses, including cold and drought, as supported by lower levels of reactive oxygen species, higher survival rate, higher activities of enzymes, relative to wild-type (WT). In addition, steady-state mRNA levels of 15 stress-responsive genes coding for either functional or regulatory proteins were higher levels in the transgenic plants relative to the WT with drought or cold treatment. yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that PbeNAC1 protein can physically interact with PbeDREB1 and PbeDREB2A. Taken together, these results demonstrate that pear PbeNAC1 plays an important role in improving stress tolerance, possibly by interacting with PbeDREB1 and PbeDREB2A to enhance the mRNA levels of some stress-associated genes.
The receptor for advanced glycation end-products (RAGE) is a multiligand membrane receptor that has been implicated in the cytotoxicity effects of β-amyloid protein (Aβ) in AD. Positive feedback mechanism of RAGE within blood-brain barrier (BBB) and/or cells inside the brain is proposed, including interaction with Aβ stimulating activation of proinflammatory cytokines, release of reactive oxygen species (ROS), which leads to neuron damage and BBB dysfunction. RAGE is the main factor mediating Aβ cytotoxicity. Attenuation of RAGE activity may inhibit Aβ from accumulation in the cerebral blood vessels and prevent neurotoxicity. Furthermore, RAGE may serve as a therapeutic target for Alzheimer's disease by inhibiting pathophysiological consequences of Aβ-RAGE interaction. Tight junctions (TJ) are identified as the basic structure of the BBB and RAGE-mediated Aβ cytotoxicity to the brain microvascular endothelial cells (BMEC), resulting in damaged BBB structural integrity. However, the potential mechanism is poorly studied.
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