Dual biomarkers-activatable hollow MnO2-Based theranostic nanoplatform for efficient breast cancer-specific multisite fluorescence imaging and synergistic therapy.

BACKGROUND: Theranostic nanoplatforms with integrated diagnostic imaging and multiple therapeutic functions play a vital role in precise diagnosis and efficient treatment for breast cancer, but unfortunately, these nanoplatforms are usually stuck in single-site imaging and single mode of treatment, causing unsatisfactory diagnostic and therapeutic efficiency. Herein, a dual biomarkers-activatable facile hollow mesoporous MnO2 (H-MnO2)-based theranostic nanoplatform, DNAzyme@H-MnO2-MUC1 aptamer (DHMM), was constructed for the simultaneous multi-site diagnosis and multiple treatment of breast cancer. RESULTS: The DHMM acted as an integrated diagnostic and therapeutic nanoplatform that realizes multi-site fluorescence imaging-guided high-efficient photothermal/chemodynamic/gene synergistic therapy (PTT/CDT/GT) for breast cancer. The H-MnO2 exhibits high loading capacity for Cy5-MUC1 aptamer (3.05 pmoL µg-1) and FAM-DNAzyme (3.37 pmoL µg-1), and excellent quenching for the probes. In the presence of MUC1 on the cell membrane and GSH in the cytoplasm, Cy5-MUC1 aptamer and FAM-DNAzyme was activated triggering dual-channel fluorescence imaging at different sites. Moreover, the self-supplied Mn2+ was further supplied as DNAzyme cofactors to catalytic cleavage intracellular EGR-1 mRNA for high-efficient GT and stimulated the Fenton-like reaction for CDT. The H-MnO2 also showcases a favorable photothermal performance with a photothermal conversion efficiency of 44.16%, which ultimately contributes to multi-site fluorescence imaging-guided synergistic treatment with an apoptosis rate of 71.82%. SIGNIFICANCE: This dual biomarker-activatable multiple therapeutic nanoplatform was realized multi-site fluorescence imaging-guided PTT/CDT/GT combination therapy for breast cancer with higher specificity and efficiency, which provides a promising theranostic nanoplatform for the precision and efficiency of breast cancer treatment.

UB2/UB3/TSH4-anchored transcriptional networks regulate early maize inflorescence development in response to simulated shade.

Increasing planting density has been adopted as an effective means to increase maize (Zea mays) yield. Competition for light from neighbors can trigger plant shade avoidance syndrome, which includes accelerated flowering. However, the regulatory networks of maize inflorescence development in response to high-density planting remain poorly understood. In this study, we showed that shade-mimicking treatments cause precocious development of the tassels and ears. Comparative transcriptome profiling analyses revealed the enrichment of phytohormone-related genes and transcriptional regulators among the genes co-regulated by developmental progression and simulated shade. Network analysis showed that three homologous Squamosa promoter binding protein (SBP)-like (SPL) transcription factors, Unbranched2 (UB2), Unbranched3 (UB3), and Tasselsheath4 (TSH4), individually exhibited connectivity to over 2,400 genes across the V3-to-V9 stages of tassel development. In addition, we showed that the ub2 ub3 double mutant and tsh4 single mutant were almost insensitive to simulated shade treatments. Moreover, we demonstrated that UB2/UB3/TSH4 could directly regulate the expression of Barren inflorescence2 (BIF2) and Zea mays teosinte branched1/cycloidea/proliferating cell factor30 (ZmTCP30). Furthermore, we functionally verified a role of ZmTCP30 in regulating tassel branching and ear development. Our results reveal a UB2/UB3/TSH4-anchored transcriptional regulatory network of maize inflorescence development and provide valuable targets for breeding shade-tolerant maize cultivars.

A DNA-Au nanomachine activated by dual types of biomarkers for multi-site imaging and gene silencing.

A programmed DNA-Au nanomachine has been constructed to achieve in situ imaging of transmembrane glycoprotein MUC1 and cytoplasmic miRNA-21 and trigger gene silencing therapy. The results of MCF-7 cell-specific imaging and apoptosis experiments demonstrate that the nanomachine provides a valuable nanotheranostic platform for accurate multi-site imaging and intracellular gene silencing.

Construction of an in vivo NIR fluorescent probe for revealing the correlation between inflammation and mitochondrial hydrogen sulfide and viscosity.

As an indispensable part of immune response, inflammation plays a critical role in the occurring and advancing of many diseases. It is reported that the emergence of inflammation can be indicated by the change of intracellular viscosity and overexpression of the hydrogen sulfide (H2S) in mitochondria. So far, elucidating the relationship between inflammation and the above parameters remains a challenge due to the lack of validated analytical tools. Herein, a novel dual-function NIR fluorescent probe CMQT with excellent biological compatibility and mitochondrial targeting ability is designed and synthesized by using 7-diethylaminocoumarin and 4-ethylphenolate quinoline acetate through twistable vinyl bonds. With the functional probe, enhanced fluorescent signals at 570 nm and 721 nm are produced in the presence of H2S and changes of viscosity. The CMQT can be applied in living cells and zebrafish, which reveals the increases of mitochondrial H2S and viscosity generated by inflammatory response through dual-channel fluorescence imaging mode. The in vivo dual-functional probe serves as an efficient tool for imaging analysis of H2S and viscosity, and has profound implications for the early diagnosis of inflammatory diseases.

Prepared carbon dots from wheat straw for detection of Cu2+ in cells and zebrafish and room temperature phosphorescent anti-counterfeiting.

The green synthesis of fluorescent carbon dots from biomass is critical for their sustainable application. Herein, using wheat straw as a single precursor, carbon dots (CDs) were prepared through a one-step carbonization process, and the obtained CDs have intense blue luminescence and excitation-independent photoluminescent behavior. The solution of CDs shows good biocompatibility, and low cytotoxicity successfully used as hopeful bioimaging and biosensing probe for Cu2+ in HepG2 cells and zebrafish. Based on CDs, boron-doped carbon dots with IPA shells (CDs@IPA) can be obtained by doping boron element and isophthalic acid (IPA) coating. CDs@IPA irradiated with different wavelength ultraviolet lamps shows different solid fluorescence, while turning off the ultraviolet lamp can produce green visible room temperature phosphorescence (RTP) to the naked eyes for 5 s. The two kinds of wheat straw-based carbon dots have bifunctional luminescence properties and can be used to detect Cu2+ and serve as RTP anti-counterfeiting signs to ensure information security.

A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease.

Alzheimer's disease (AD) is one of the major worldwide causes of dementia that is characterized by irreversible decline in learning, memory loss, and behavioral impairments. Mitophagy is selective autophagy through the clearance of aberrant mitochondria, specifically for degradation to maintain energy generation and neuronal and synaptic function in the brain. Accumulating evidence shows that defective mitophagy is believed to be as one of the early and prominent features in AD pathogenesis and has drawn attention in the recent few years. APOE ε4 allele is the greatest genetic determinant for AD and is widely reported to mediate detrimental effects on mitochondria function and mitophagic process. Given the continuity of the physiological process, this review takes the mitochondrial dynamic and mitophagic core events into consideration, which highlights the current knowledge about the molecular alterations from an APOE-genotype perspective, synthesizes ApoE4-associated regulations, and the cross-talk between these signaling, along with the focuses on general autophagic process and several pivotal processes of mitophagy, including mitochondrial dynamic (DRP1, MFN-1), mitophagic induction (PINK1, Parkin). These may shed new light on the link between ApoE4 and AD and provide novel insights for promising mitophagy-targeted therapeutic strategies for AD.