Molecular Insight into the Pozzolanic Reaction of Metakaolin and Calcium Hydroxide.

The reaction mechanism of the pozzolanic reaction of metakaolin (MK) from the atomic point of view has not yet been explored. To explain the process and mechanism of the pozzolanic reaction from the atomic point of view, molecular insight into the pozzolanic reaction of MK and calcium hydroxide (CH) was analyzed through the reaction molecular dynamics (MD) simulation. The results show that the pozzolanic reaction of MK and CH can be essentially regarded as the CH decomposition and penetration into MK. Also, the structure evolution after the pozzolanic reaction shows that the water molecules cannot penetrate the MK structure till the participation of Ca2+ and OH- ions of CH. The Ca2+ and OH- ions have strong interaction with MK and drill into the MK structure, followed by the destruction of a part of the MK structure and water penetration. The final structure of CH removed by MK can be regarded as the precursor of the CASH gel structure.

In-situ construction of fluorescent probes for hydrogen peroxide detection in mitochondria and lysosomes with on-demand modular assembling and double turn-on features.

Due to the diverse H2O2 distribution in organelles, fluorescent probes were usually required to be prepared separately, which limited the convenience and practicability. Herein, we reported a flexible strategy to in-situ construct H2O2 fluorescent probes in different organelles. A tetrazine fused probe TP was developed with rapid click reaction capacity and sensitive H2O2 response. When treated with H2O2, the turn-on fluorescence was effectively quenched by the tetrazine part. Only after click reaction with dienophiles, the fluorescence resumed. In application, cells were firstly treated with triphenylphosphorus tagged norbornene (TPP-NB) to label mitochondria, which was followed by the introduction of probe TP to trigger click reaction. The in-situ constructed probe P1 served as a local H2O2 sensor. In a similar way, probe P2 was in-situ constructed in lysosomes via probe TP and morpholine tagged norbornene (MP-NB). With this on-demand modular assembling and double turn-on features, our strategy to construct fluorescent probes presented high flexibility and anti-interference performance, which was expected to inspired more applications in biological studies.

Machine-learning screening of luminogens with aggregation-induced emission characteristics for fluorescence imaging.

Due to the excellent biocompatible physicochemical performance, luminogens with aggregation-induced emission (AIEgens) characteristics have played a significant role in biomedical fluorescence imaging recently. However, screening AIEgens for special applications takes a lot of time and efforts by using conventional chemical synthesis route. Fortunately, artificial intelligence techniques that could predict the properties of AIEgen molecules would be helpful and valuable for novel AIEgens design and synthesis. In this work, we applied machine learning (ML) techniques to screen AIEgens with expected excitation and emission wavelength for biomedical deep fluorescence imaging. First, a database of various AIEgens collected from the literature was established. Then, by extracting key features using molecular descriptors and training various state-of-the-art ML models, a multi-modal molecular descriptors strategy has been proposed to extract the structure-property relationships of AIEgens and predict molecular absorption and emission wavelength peaks. Compared to the first principles calculations, the proposed strategy provided greater accuracy at a lower computational cost. Finally, three newly predicted AIEgens with desired absorption and emission wavelength peaks were synthesized successfully and applied for cellular fluorescence imaging and deep penetration imaging. All the results were consistent successfully with our expectations, which demonstrated the above ML has a great potential for screening AIEgens with suitable wavelengths, which could boost the design and development of novel organic fluorescent materials.

Molecular Insights into the Reaction Process of Alkali-Activated Metakaolin by Sodium Hydroxide.

When metakaolin (MK) is alkalized with an alkaline activator, it depolymerizes under the action of the alkali. However, the process of MK alkalinization is still unrevealed. Here, we supplied a molecular insight into the process of MK alkalinization through reaction molecular dynamics (MD) simulation. The structure, dynamics, and process of MK alkalinization are systematically investigated. The results showed that the layered structure of MK was destroyed and the silicates in MK were dissolved by sodium hydroxide solution during the alkalinization reaction of MK. The aluminates in MK are not dissolved, indicating that aluminates are more stable than silicates. Moreover, the equilibrium structures of MK with H2O and MK with NaOH solution show that only when both sodium hydroxide and water are involved in the alkalinization reaction, the silicates in MK undergo depolymerization. Also, the observed final state of MK alkalinization can be recognized as the precursor of alkali-activated materials (AAMs).

Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.

The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm's canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ∼1 µm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm's canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in glaucoma.

Metal organic framework-coated gold nanorod as an on-demand drug delivery platform for chemo-photothermal cancer therapy.

Chemo-photothermal therapy based on nanoparticles has emerged as a promising strategy for cancer treatment. However, its therapeutic efficacy and application potential are largely subjected to the uncontrollability and biotoxicity of functional nanoplatforms. Herein, a novel biocompatible and biodegradable metal organic framework (MOF), which was constructed by growing crystalline zeolitic imidazolate framework-8 on gold nanoroad (Au@ZIF-8), was designed and fabricated for efficient drug loading and controlled release. Owing to the large surface area and guest-matching pore size of ZIF-8, doxorubicin (DOX) was successfully loaded into the Au@ZIF-8 with a high drug loading efficiency of ~ 37%. Under NIR light or weakly acidic environment, the ZIF-8 layer was quickly degraded, which resulted in an on-demand drug release in tumour site. More importantly, under the irradiation of near infrared (NIR) laser, highly efficient cancer treatment was achieved in both in vitro cell experiment and in vivo tumour-bearing nude mice experiment due to the synergistic effect of photothermal (PTT) therapy and chemotherapy. In addition, the in vivo study revealed the good biocompatibility of Au@ZIF-8. This work robustly suggested that Au@ZIF-8 could be further explored as a drug delivery system for chemo-photothermal synergistic therapy.

Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy.

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression.

Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting. Recent discoveries in the genetic and epigenetic determinants of BTIC tumorigenesis offer novel opportunities for RNAi-mediated targeting of BTICs. Here we show that BTIC growth arrest in vitro and in vivo is accomplished via concurrent siRNA knockdown of four transcription factors (SOX2, OLIG2, SALL2, and POU3F2) that drive the proneural BTIC phenotype delivered by multiplexed siRNA encapsulation in the lipopolymeric nanoparticle 7C1. Importantly, we demonstrate that 7C1 nano-encapsulation of multiplexed RNAi is a viable BTIC-targeting strategy when delivered directly in vivo in an established mouse brain tumor. Therapeutic potential was most evident via a convection-enhanced delivery method, which shows significant extension of median survival in two patient-derived BTIC xenograft mouse models of GBM. Our study suggests that there is potential advantage in multiplexed targeting strategies for BTICs and establishes a flexible nonviral gene therapy platform with the capacity to channel multiplexed RNAi schemes to address the challenges posed by tumor heterogeneity.

Leakage behavior of toxic substances of naphthalene sulfonate-formaldehyde condensation from cement based materials.

Naphthalene sulfonate-formaldehyde condensatation (NSF) is the main component of the naphthalene based water reducers for cement based materials, as well as an organic substance with potential toxicity. However it is still uncertain whether it can leak from the cement based materials. In this work, the leakage ratio and adsorption behavior of NSF from various cement based materials such as the different water/cement (w/c) ratio, NSF content, types of cementitious materials as well as at different hydration time were evaluated. The product components of the cement based materials cured for different times were also quantified to explore the mechanisms which are responsible for the leakage and adsorption behaviors. The results indicate that more NSF, lower w/c ratio and less mineral admixture decrease the NSF leakage ratio. The leakage ratio of NSF from cement paste mixed 0.3% NSF is up to 50.8% at 0.5 h, and it decreases to 31.0% at 28 d. The leakage ratio of NSF from cement paste decreases as the hydration time prolongs. The lower leakage ratio corresponds to the higher adsorption capacity. Less adsorption capacity and thinner adsorption film imply that lower temperature and mineral admixture decrease the NSF adsorption behavior. When 0.3% NSF is added into the cement paste, the adsorption amount and NSF layer thickness are 5.53 mg/g and 0.98 nm, 5.87 mg/g and 4.7  nm at 0.5 h and 28 d respectively. The result demonstrates that the adsorption behavior of NSF in cement significantly increases at the initial several hours and gradually stabilizes after the first day. The X-ray powder diffractometer (XRD) results show that the contents of tricalcium silicate (C3S) and dicalcium silicate (C2S) continuously decline and the amorphous phases and ettringite (AFt) increase rapidly in the early stage. NSF adsorption and leakage behaviors are closely related to the hydration process of cement. These results indicate that NSF can definitely leak from the cement based materials and thus the NSF potential environmental pollution cannot be ignored. At least, it should be restricted or cautious to produce the water tower and pipe concrete structure with it. These results will sever as a theoretically reference for the pollution control as well as better application of NSF in cement-based materials.

Multicolor super-resolution imaging using spectroscopic single-molecule localization microscopy with optimal spectral dispersion.

We developed transmission diffraction grating-based spectroscopic single-molecule localization microscopy (sSMLM) to collect the spatial and spectral information of single-molecule blinking events concurrently. We characterized the spectral heterogeneities of multiple far-red emitting dyes in a high-throughput manner using sSMLM. We also investigated the influence of spectral dispersion on the single-molecule identification performance of fluorophores with large spectral overlapping. The careful tuning of spectral dispersion in grating-based sSMLM permitted simultaneous three-color super-resolution imaging in fixed cells with a single objective lens at a relatively low photon budget. Our sSMLM has a compact optical design and can be integrated with conventional localization microscopy to provide add-on spectroscopic analysis capability.

Superresolution intrinsic fluorescence imaging of chromatin utilizing native, unmodified nucleic acids for contrast.

Visualizing the nanoscale intracellular structures formed by nucleic acids, such as chromatin, in nonperturbed, structurally and dynamically complex cellular systems, will help expand our understanding of biological processes and open the next frontier for biological discovery. Traditional superresolution techniques to visualize subdiffractional macromolecular structures formed by nucleic acids require exogenous labels that may perturb cell function and change the very molecular processes they intend to study, especially at the extremely high label densities required for superresolution. However, despite tremendous interest and demonstrated need, label-free optical superresolution imaging of nucleotide topology under native nonperturbing conditions has never been possible. Here we investigate a photoswitching process of native nucleotides and present the demonstration of subdiffraction-resolution imaging of cellular structures using intrinsic contrast from unmodified DNA based on the principle of single-molecule photon localization microscopy (PLM). Using DNA-PLM, we achieved nanoscopic imaging of interphase nuclei and mitotic chromosomes, allowing a quantitative analysis of the DNA occupancy level and a subdiffractional analysis of the chromosomal organization. This study may pave a new way for label-free superresolution nanoscopic imaging of macromolecular structures with nucleotide topologies and could contribute to the development of new DNA-based contrast agents for superresolution imaging.

Effect of Oxidization Temperatures and Aging on Performance of Carbonate Melt Oxidized Iridium Oxide pH Electrode.

Iridium oxide pH electrodes employing the carbonate melt oxidation method were fabricated with oxidation temperatures of 750 °C, 800 °C and 850 °C, respectively. Scanning electron microscope (SEM) and atomic force microscope (AFM) images showed that the oxide film regularized with the increase in oxidation temperatures. The pH response, response time and long-term stability of the electrodes indicated that the electrodes made at 850 °C had the best performance. X-ray photoelectron spectra (XPS) surveys investigated the change in the electrodes' chemical composition and element oxidation states at 850 °C, and the results showed that the relative content of Ir3+ had increased by 23.9%, and the Ir4+ and Ir6+ had decreased by 10.9% and 13%, respectively, in the surface oxide layer after one month of aging. However, the relative contents of Ir3+, Ir4+ and Ir6+ were almost constant for the inner oxide layer. Meanwhile, the XPS result also indicated that the outer oxide layer of the electrode had a higher hydration degree than the inner oxide layer.

Patterned-illumination second harmonic generation microscopy of collagen fibrils in rat scleras.

We developed a patterned-illumination second harmonic generation (PI-SHG) microscopy, which combines the principle of structured illumination reconstruction with SHG microscopy for label-free super-resolution imaging. We confirmed that PI-SHG microscopy can achieve 1.59-time resolution improvement compared to conventional SHG microscopy by imaging nanowire samples. We further demonstrated three-dimensional PI-SHG microscopy in imaging ex vivo collagen fibrils in rat scleras.

Sub-10-nm imaging of nucleic acids using spectroscopic intrinsic-contrast photon-localization optical nanoscopy (SICLON).

Elucidating chromatin structure in vitro requires resolution below 10 nm to visualize the mononucleosome has been an ongoing challenge. In this work, we achieve sub-10-nm imaging of nucleic acids via spectroscopic intrinsic-contrast photon-localization optical nanoscopy (SICLON) without the use of external labels. SICLON leverages two key innovations: using endogenous nucleotides as the emission source and a custom-made imaging system that can simultaneously record the position and optical spectra of emitting molecules. With a novel spectral regression algorithm that identifies the spectroscopic fingerprints of neighboring molecules that were previously indistinguishable, we demonstrate the utility of SICLON by visualizing unlabeled poly-nucleotides and linear single-stranded DNA fibers with a resolution of 6.2 nm.

Stochastic fluorescence switching of nucleic acids under visible light illumination.

We report detailed characterizations of stochastic fluorescence switching of unmodified nucleic acids under visible light illumination. Although the fluorescent emission from nucleic acids under the visible light illumination has long been overlooked due to their apparent low absorption cross section, our quantitative characterizations reveal the high quantum yield and high photon count in individual fluorescence emission events of nucleic acids at physiological concentrations. Owing to these characteristics, the stochastic fluorescence switching of nucleic acids could be comparable to that of some of the most potent exogenous fluorescence probes for localization-based super-resolution imaging. Therefore, utilizing the principle of single-molecule photon-localization microscopy, native nucleic acids could be ideal candidates for optical label-free super-resolution imaging.

Gigahertz All-Optical Modulation Using Reconfigurable Nanophotonic Metamolecules.

We report the design of reconfigurable metamolecules consisting a large array of nanowire featuring U-shaped cross section. These nanoscale metamolecules support colocalized electromagnetic resonance at optical frequencies and mechanical resonance at GHz frequencies with a deep-subdiffraction-limit spatial confinement (∼λ2/100). The coherent coupling of those two distinct resonances manifests a strong optical force, which is fundamentally different from the commonly studied forms of radiation forces, gradient forces, or photothermal induced deformation. The strong optical force acting upon the built-in compliance further sets the stage for allowing the metamolecules to dynamically change their optical properties upon the incident light. The all-optical modulation at the frequency at 1.8 GHz has thus been demonstrated experimentally using a monolayer of metamolecules. The metamolecules were conveniently fabricated using complementary metal-oxide-semiconductor-compatible metal deposition and nanoimprinting processes and thus offer promising potential in developing integrated all-optical modulator.

Scalable nanofabrication of U-shaped nanowire resonators with tunable optical magnetism.

Split ring resonators have been studied extensively in reconstituting the diminishing magnetism at high electromagnetic frequencies in nature. However, breakdown in the linear scaling of artificial magnetism is found to occur at the near-infrared frequency mainly due to the increasing contribution of self-inductance while reducing dimensions of the resonators. Although alternative designs have enabled artificial magnetism at optical frequencies, their sophisticated configurations and fabrication procedures do not lend themselves to easy implementation. Here, we report scalable nanofabrication of U-shaped nanowire resonators (UNWRs) using the high-throughput nanotransfer printing method. By providing ample area for conducting oscillating electric current, UNWRs overcome the saturation of the geometric scaling of the artificial magnetism. We experimentally demonstrated coarse and fine tuning of LC resonances over a wide wavelength range from 748 nm to 1600 nm. The added flexibility in transferring to other substrates makes UNWR a versatile building block for creating functional metamaterials in three dimensions.

Single all-fiber-based nanosecond-pulsed supercontinuum source for multispectral photoacoustic microscopy and optical coherence tomography.

We report the usefulness of a single all-fiber-based supercontinuum (SC) source for combined photoacoustic microscopy (PAM) and optical coherence tomography (OCT). The SC light is generated by a tapered photonic crystal fiber pumped by a nanosecond pulsed master oscillator power amplifier at 1064 nm. The spectrum is split into a shorter wavelength band (500-800 nm) for single/multi-spectral PAM and a longer wavelength band (800-900 nm) band for OCT. In vivo mouse ear imaging was achieved with an integrated dual-modality system. We further demonstrated its potential for spectroscopic photoacoustic imaging by doing multispectral measurements on retinal pigment epithelium and blood samples with 15-nm linewidth.

Amorphous diamond-structured photonic crystal in the feather barbs of the scarlet macaw.

Noniridescent coloration by the spongy keratin in parrot feather barbs has fascinated scientists. Nonetheless, its ultimate origin remains as yet unanswered, and a quantitative structural and optical description is still lacking. Here we report on structural and optical characterizations and numerical simulations of the blue feather barbs of the scarlet macaw. We found that the sponge in the feather barbs is an amorphous diamond-structured photonic crystal with only short-range order. It possesses an isotropic photonic pseudogap that is ultimately responsible for the brilliant noniridescent coloration. We further unravel an ingenious structural optimization for attaining maximum coloration apparently resulting from natural evolution. Upon increasing the material refractive index above the level provided by nature, there is an interesting transition from a photonic pseudogap to a complete bandgap.

Photoacoustic probe using a microring resonator ultrasonic sensor for endoscopic applications.

We designed an all-optical photoacoustic (PA) probe for endoscopic applications by employing an optically transparent, coverslip-type, polymeric microring resonator ultrasonic sensor. We experimentally quantified the axial, tangential, and radial resolutions and angular sensitive stability of this probe. Using this probe, we achieved volumetric imaging of several phantoms. Our all-optical probe design offers clear benefit in integrating PA endoscope with other optical endoscopic imaging modalities to facilitate the transformation from bench to bedside.