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Matrix metalloproteinase (MMP) secretion is highly associated with tumor invasion and metastasis; therefore, monitoring MMP secretion is important for disease progression study and therapy choosing. Though working well for intracellular MMP imaging, the performance of current MMP detection probes is impaired in secretion monitoring due to the diffusion of MMP in an extracellular environment after secretion and low secreted amount. Here, we design a cell membrane-anchored ratiometric upconversion nanoprobe (UCNPs-Cy3/Pep-QSY7/Ab) for in situ MMP secretion visualization. Anti-EGFR is functionalized on the nanoprobe to provide specific recognition to tumor cells and guarantee fast response to MMP2 in the local place of secretion. MMP-responsive cleavage of Pep-QSY7 results in Cy3 luminescence recovery at 580 nm, which is ratioed over an internal standard of UCNP emission at 654 nm for MMP2 detection. The presented cell membrane-anchored ratiometric upconversion nanoprobe demonstrated that satisfactory results for in situ monitoring of MMP2 secretion from MDA-MB-231 cells and MCF-7 cells, as well as in vivo imaging of metastatic lymph nodes, would provide a universal platform for protease secretion study and contribute to tumor invasiveness assessment.The lack of specific-targeting therapy to precisely identify and kill malignant cells while sparing others is a great challenge in colorectal cancer (CRC) treatment. In the era of molecular classification of tumors, CRC has been grouped into four Consensus Molecular Subtypes. Accounting for 37% of all types, the CMS2 group (canonical type) shows distinguishing features WNT and MYC signaling activation. In this study, we designed an RNA-only delivery kill switch to specifically eliminate CMS2 type CRC cells. The sensing and logic processing functions are integrated by the newly engineered L7Ae, which can not only detect the stability of β-catenin protein and the presence of cytoplasm located Myc/Myc-nick, but also do logic computation. The circuit specifically eliminated HCT-116 cells while sparing other kinds of cells, showing a proof-of-principle approach to precisely target CMS2 type CRC.Microbial contamination and the prevalence of resistant bacteria is considered a worldwide public health problem. Therefore, recently, great efforts have been made to develop photoresponsive platforms for the simultaneous photodynamic antibacterial (PDA) and photothermal antibacterial (PTA) therapy processes as mediated by specific light. However, owing to the absorption mismatches of the photothermal agents and photodynamic photosensitizers, it has been discovered that many synergistic photoresponsive antibacterial platforms cannot be excited by a single-wavelength light. In this study, silver bismuth sulfide quantum dots (AgBiS2 QDs) identified from the literature as a near-infrared light (NIR) that triggers bifunctional materials with simultaneous photodynamic and photothermal effects for photoresponsive bacterial killing were used. Specifically, AgBiS2 QDs were successfully synthesized via a bottom-up approach, using polyethylenimine (PEI) as an assistant molecule. With PEI wrapping, the attachment between the negatively charged membrane surfaces of the bacterial cells and AgBiS2 QDs was enhanced via the electrostatic interactions. The photodriven antibacterial activity of AgBiS2 QDs was then investigated against both S. aureus and E. coli. The results revealed a significant reduction in bacterial survival. The killing effect was found to be independent of the AgBiS2 QDs, and redox potentials controlled the photogenerated electrons that thermodynamically favored the formation of multiple reactive oxygen species (ROS). Eeyarestatin 1 nmr A possible phototriggered antibacterial mechanism was then proposed in which the AgBiS2 QDs are anchored first to the bacterial surface and then induce breaking on its outer membrane by high local heat and ROS under single 808 nm NIR laser illumination to finally induce bacterial death.Adenosine Deaminases Acting on RNA (ADARs) convert adenosine to inosine in double stranded RNA. Human ADARs can be directed to predetermined target sites in the transcriptome by complementary guide strands, allowing for the correction of disease-causing mutations at the RNA level. Here we use structural information available for ADAR2-RNA complexes to guide the design of nucleoside analogs for the position in the guide strand that contacts a conserved glutamic acid residue in ADARs (E488 in human ADAR2), which flips the adenosine into the ADAR active site for deamination. Mutating this residue to glutamine (E488Q) results in higher activity because of the hydrogen bond donating ability of Q488 to N3 of the orphan cytidine on the guide strand. We describe the evaluation of cytidine analogs for this position that stabilize an activated conformation of the enzyme-RNA complex and increase catalytic rate for deamination by the wild-type enzyme. A new crystal structure of ADAR2 bound to duplex RNA bearing a cytidine analog revealed a close contact between E488, stabilized by an additional hydrogen bond and altered charge distribution when compared to cytidine. In human cells and mouse primary liver fibroblasts, this single nucleotide modification increased directed editing yields when compared to an otherwise identical guide oligonucleotide. Our results show that modification of the guide RNA can mimic the effect of hyperactive mutants and advance the approach of recruiting endogenous ADARs for site-directed RNA editing.When dealing with reactions of a liquid reactant and a solid catalyst, macroreactors with vigorous stirring equipment may be dangerous and cause wastage of energy. Reducing the diffusion distance and promoting reactants to reach the catalyst surface for efficient reaction remain the key challenges. Here, inspired by capillary-driven water motion in plants, we propose to implement a self-driven multiplex reaction (SMR) in nanocatalyst-loaded microchannels. Unlike the classical capillary rise, the droplet in SMR has variable pressure difference, leading to tunable flow velocity for controlling the reaction rate without any auxiliary equipment. The SMR in microchannels contributes to an increase in the reaction rate by more than 2 orders of magnitude compared to that in macroreactors. Specifically, this strategy reduces the reaction volume by 170 times, the catalyst usage by about 12 times, and the energy consumption by 50 times. This apparatus with a small volume and less catalyst content promises to provide an efficient strategy for the precise manipulation of chemical reactions.
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