Rational Design of Quinoxalinone-Based Red-Emitting Probes for High-Affinity and Long-Term Visualizing Amyloid‑β In Vivo

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with insidious onset, and the deposition of amyloid-β (Aβ) is believed to be one of the main cause. Fluorescence imaging is a promising technique for this task, but the Aβ gold standard probe ThT developed based on this still has shortcomings. The development of a new fluorescent probe to detect Aβ plaques is thought to be essential. Herein, a series of red to near-infrared emitting fluorescent probes QNO-ADs with newly quinoxalinone skeleton are designed to detect Aβ plaques. They all demonstrate excellent optical properties and high binding affinity (∼Kd = 20 nM) to Aβ aggregates. As the most outstanding candidate, QNO-AD-3 shows significant signal-to-noise (S/N) ratio at the level of in vitro binding studies, and the brilliant fluorescence staining results in favor of grasping the approximate distribution of Aβ plaques in the brain slice. In vivo Aβ plaques imaging suggests that QNO-AD-3 can cross the BBB and have a long retention time in the brain with low biological toxicity. In addition, the results of docking theoretical calculation also provide some references for the design of Aβ probe. Overall, given the high affinity of QNO-AD-3 and the ability to monitor Aβ plaques for a long time that is not common now, we believe QNO-AD-3 will be an effective tool for an Aβ-related matrix and AD disease research in the future

Additional file 1 of Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis

Additional file 1: Fig. S1. Nanoplatform characterisation. (a) Sizes and (b) ζ-potentials of HMON NPs, Fe-HMON NPs, Fe-HMON-PEG NPs, and Fe-HMON-Tf NPs. (c) Nitrogen sorption isotherms and (d) pore size distribution curves for Fe-HMON NPs. Fig. S2. Nanoplatform composition. (a) Coomassie Blue analysis of particles after transferrin modification with UV–vis spectroscopy. Fe-HMON-Tf NPs stained blue while Fe-HMON-PEG NPs stained green. (b) FTIR spectra of HMON NPs, Fe-HMON NPs, Fe-HMON-PEG NPs, and Fe-HMON-Tf NPs. Fig. S3. TEM images of DOX@Fe-HMON-Tf NPs after biodegradation in FBS at 1d, 3d, 5d, 7d, and 14d. Scale bar = 100 nm. Fig. S4. Cell viability under different treatments. (a) Cytotoxicity of HMON-Tf NPs and Fe-HMON-Tf NPs after incubation with LO2 cells for 24h. ****P < 0.0001, two-tailed t test; mean ± SD. (b) Cytotoxicity of HMON-Tf NPs and Fe-HMON-Tf NPs after incubation with HepG2 cancer cells for 24 h. ****P < 0.0001, two-tailed t test; mean ± SD. (c) Cell viability of HepG2 cells treated with PBS, DOX, HMON-Tf NPs, Fe-HMON-Tf NPs, DOX@HMON-Tf NPs, DOX@Fe-HMON-PEG NPs or DOX@Fe-HMON-Tf NPs at different DOX dosage. Fig. S5. H2O2 levels in tumor tissue and changes in the intracellular lipid ROS levels after different treatments. (a) Western blot analysis on the expression of HIF-1α in HepG2 cells cultured in a normoxic environment and a hypoxic environment. (b) H2O2 levels of tumor tissues extracted from HepG2 tumor–bearing mice after the treatment with varied concentrations of DOX. n = 6; ****P < 0.0001, two-tailed t test; mean with SD. (c) Flow cytometric analysis and (d) CLSM observation on the intracellular lipoperoxide levels in HepG2 cells incubated with varied concentrations of DOX for 24h. Scale bar = 50um. (e) MDA levels in HepG2 cells incubated with PBS, DOX, HMON-Tf NPs, Fe-HMON-Tf NPs, DOX@HMON-Tf NPs, DOX@Fe-HMON-PEG NPs and DOX@Fe-HMON-Tf NPs for 24h. ***P < 0.001; ****P < 0.0001, two-tailed t test; mean ± SD. Fig. S6. Body weight changes of mice after different treatments and the corresponding in vivo biosafety evaluation. (a) Changes in the average body weight of tumor-bearing mice through the 21-day treatment period, which were recorded every 2 days. (b) Red blood cell (RBC); (c) white blood cell (WBC); (d) hemoglobin (HGB) and (e) blood platelet (PLT). (f) Blood levels of ALT, AST and ALP as liver function markers. (g) Blood urea nitrogen (BUN) and (h) creatinine (CREA) represent as kidney function markers. n = 6; mean ± SD. (i) Histological analysis of the major organs (lung, liver, spleen, kidney, heart) extracted from HepG2 -tumor bearing mice after the 21 days treatment with PBS, DOX, HMON-Tf NPs, Fe-HMON-Tf NPs, DOX@HMON-Tf NPs, DOX@Fe-HMON-PEG NPs and DOX@Fe-HMON-Tf NPs, for which the organ slices were processed for H&E staining. Scale bar = 100um

Super-Resolution Exciton Imaging of Nanobubbles in 2D Semiconductors with Near-Field Nanophotoluminescence Microscopy

Two-dimensional (2D) semiconductors, such as transition metal dichalcogenides, have emerged as important candidate materials for next-generation chip-scale optoelectronic devices with the development of large-scale production techniques, such as chemical vapor deposition (CVD). However, 2D materials need to be transferred to other target substrates after growth, during which various micro- and nanoscale defects, such as nanobubbles, are inevitably generated. These nanodefects not only influence the uniformity of 2D semiconductors but also may significantly alter the local optoelectronic properties of the composed devices. Hence, super-resolution discrimination and characterization of nanodefects are highly demanded. Here, we report a near-field nanophotoluminescence (nano-PL) microscope that can quickly screen nanobubbles and investigate their impact on local excitonic properties of 2D semiconductors by directly visualize the PL emission distribution with a very high spatial resolution of ∼10 nm, far below the optical diffraction limit, and a high speed of 10 ms/point under ambient conditions. By using nano-PL microscopy to map the exciton and trion emission intensity distributions in transferred CVD-grown monolayer tungsten disulfide (1L-WS2) flakes, it is found that the PL intensity decreases by 13.4% as the height of the nanobubble increases by every nanometer, which is mainly caused by the suppression of trion emission due to the strong doping effect from the substrate. In addition to the nanobubbles, other types of nanodefects, such as cracks, stacks, and grain boundaries, can also be characterized. The nano-PL method is proven to be a powerful tool for the nondestructive quality inspection of nanodefects as well as the super-resolution exploration of local optoelectronic properties of 2D materials

Additional file 1 of Ultra-thin layered double hydroxide-mediated photothermal therapy combine with asynchronous blockade of PD-L1 and NR2F6 inhibit hepatocellular carcinoma

Additional file 1: Figure S1. Size distribution of CCF-LDH in three mediums. Figure S2. Stability tests of CCF-LDHs in PBS, water and 1640 by monitoring particle size for 7 days. Error bars stand for ± SD (n = 3). Figure S3. XRD pattern of CCF-LDHs nanosheets. Figure S4. EDS of the CCF-LDHs. Figure S5. 1H NMR spectrum of PEG-DMMA. Figure S6. FTIR spectra. Figure S7. HRTEM image of C@P (Scale bar = 100 nm). Figure S8. Temperature elevation of C@P (100 μg/mL) under 808 nm NIR laser with different irradiation power in pH 6.5. Figure S9. Thermal infrared images of C@P (100 μg/mL) in tubes. Figure S10. HRTEM image of CCF-LDHs-siRNA. Scale bar = 100 nm. Figure S11. Zeta potential of CCF-LDHs-siRNA. Figure S12. Stability tests of CS@P in PBS, water and 1640 (with and without FBS) by monitoring particle size for 7 days. Digital photos of CCF-LDHs, C@P, and CS@P in 1640 with 10% FBS (bottom left). Error bars stand for ± SD (n = 3). Figure S13. The confocal images of intracellular localization of fluorescent FITC-CS@P in H22 and T cells for 4 h. Scale bar = 10 μm. Figure S14. The fluorescence intensity of FITC in H22 cell after the indicated treatments. Figure S15. In vitro cell viability of H22 tumor cells incubated with C@P for 24h. Figure S16. In vitro cell viability of H22 tumor cells incubated with C@P for 24h with laser irradiation (300s, 1 W cm−2). Figure S17. Fluorescence images of H22 tumor-bearing mice pre, 6, 12, 24, and 48 postinjection with CS or CS@P. Figure S18. Ex vivo fluorescence images of harvested organs and tumors at 48 h after the indicated treatments. Figure S19. In vivo MR imaging before and after intravenous injection of CS@P (dose:1 mg kg−1) within 48h. Figure S20. Thermal images of tumor-bearing mice injected with PBS and C@P, respectively, with irradiation. Figure S21. The tumor digital images obtained from H22 tumor-bearing mice on day 21 after treatment treated with PBS, aPD-L1, C@P, C@P + Laser, C@P + Laser + aPD-L1, CS@P, CS@P + Laser, and CS@P + Laser + aPD-L1. Figure S22. Survival curves of H22 tumor-bearing mice in different groups (n = 6). Figure S23. Change in body weight after the indicated treatment. Figure S24. H&E staining of the major organs. Figure S25. Flow cytometry analysis of the CD44 and CD62L expressions on primary tumor sites (a) and spleens (b) with various treatments (gated on CD3+CD8+)

Regulation Mechanism of Phenolic Hydroxyl Number on Self-Assembly and Interaction between Edible Dock Protein and Hydrophobic Flavonoids

In this study, galangin (Gal), kaempferol (Kae), quercetin (Que), and myricetin (Myr) were chosen as the representative flavonoids with different phenolic hydroxyl numbers in the B-ring. The edible dock protein (EDP) was chosen as the new plant protein. Based on this, the regulation mechanism of the phenolic hydroxyl number on the self-assembly behavior and molecular interaction between EDP and flavonoid components were investigated. Results indicated that the loading capacity order of flavonoids within the EDP nanomicelles was Myr (10.92%) > Que (9.56%) > Kae (6.63%) > Gal (5.55%). Moreover, this order was consistent with the order of the hydroxyl number in the flavonoid’s B ring: Myr (3) > Que (2) > Kae (1) > Gal (0). The micro morphology exhibited that four flavonoid-EDP nanomicelles had a core–shell structure. In the meantime, the EDP encapsulation remarkably improved the flavonoids’ water solubility, storage stability, and sustained release characteristics. During the interaction of EDP and flavonoids, the noncovalent interactions including van der Waals forces, hydrophobic interaction, and hydrogen bonding were the main binding forces. All of the results demonstrated that the hydroxyl number of bioactive compounds is a critical factor for developing a delivery system with high loading ability and stability

Quantum Emitters with Narrow Band and High Debye–Waller Factor in Aluminum Nitride Written by Femtosecond Laser

Solid-state quantum emitters (QEs) are central components for photonic-based quantum information processing. Recently, bright QEs in III-nitride semiconductors, such as aluminum nitride (AlN), have attracted increasing interest because of the mature commercial application of the nitrides. However, the reported QEs in AlN suffer from broad phonon side bands (PSBs) and low Debye–Waller factors. Meanwhile, there is also a need for more reliable fabrication methods of AlN QEs for integrated quantum photonics. Here, we demonstrate that laser-induced QEs in AlN exhibit robust emission with a strong zero phonon line, narrow line width, and weak PSB. The creation yield of a single QE could be more than 50%. More importantly, they have a high Debye–Waller factor (>65%) at room temperature, which is the highest result among reported AlN QEs. Our results illustrate the potential of laser writing to create high-quality QEs for quantum technologies and provide further insight into laser writing defects in relevant materials

Super stealth dicing of transparent solids with nanometric precision

Laser cutting of semiconductor wafers and transparent dielectrics has become a dominant process in manufacturing industries, encompassing a wide range of applications from flat display panels to microelectronic chips. Limited by Heisenberg's uncertainty principle imposed on the beam width and its longitudinal extend of laser focus, a trade-off must be made between cutting accuracy and aspect ratio in conventional laser processing, with accuracy typically approaching a micron and the aspect ratio on the order of $10^2$. Herein, we propose a method to circumvent this limitation. It is based on the laser modification induced by a back-scattering interference crawling mechanism, which creates a positive feedback for homogenizing longitudinal energy deposition and lateral sub-wavelength light confinement during laser-matter interaction. Consequently, cutting width on the scale of tens of nanometers and aspect ratio $\sim 10^4$ were simultaneously achieved. We refer to this technique as ``super stealth dicing'', which is based on an analytical model and validated through numerical simulations, ensuring its broad applicability. It can be applied to various transparent functional solids, such as glass, laser crystal, ferroelectric, and semiconductor, and is elevating the precision of future advanced laser dicing, patterning, and drilling into the nanometric era