A Nanozyme-Boosted MOF-CRISPR Platform for Treatment of Alzheimer's Disease.

Rectifying the aberrant microenvironment of a disease through maintenance of redox homeostasis has emerged as a promising perspective with significant therapeutic potential for Alzheimer's disease (AD). Herein, we design and construct a novel nanozyme-boosted MOF-CRISPR platform (CMOPKP), which can maintain redox homeostasis and rescue the impaired microenvironment of AD. By modifying the targeted peptides KLVFFAED, CMOPKP can traverse the blood-brain barrier and deliver the CRISPR activation system for precise activation of the Nrf2 signaling pathway and downstream redox proteins in regions characterized by oxidative stress, thereby reinstating neuronal antioxidant capacity and preserving redox homeostasis. Furthermore, cerium dioxide possessing catalase enzyme-like activity can synergistically alleviate oxidative stress. Further in vivo studies demonstrate that CMOPKP can effectively alleviate cognitive impairment in 3xTg-AD mouse models. Therefore, our design presents an effective way for regulating redox homeostasis in AD, which shows promise as a therapeutic strategy for mitigating oxidative stress in AD.

ARTIFICIAL INTELLIGENCE FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-BASED DISEASE ACTIVITY PREDICTION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans. METHODS: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories. RESULTS: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was 0.4286 active choroidal neovascularization, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, and 0.9762, respectively. The overall AI classification prediction was significantly better than the human (odds ratio = 1.95, P = 0.0021). CONCLUSION: These data show that choroidal neovascularization morphology can be used to predict disease activity by AI; longitudinal studies are needed to better understand the evolution of choroidal neovascularization and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.

Hydrogen-bonded organic frameworks: new horizons in biomedical applications.

Hydrogen-bonded organic frameworks (HOFs) are an emerging attractive class of highly crystalline porous materials characterized by significant biocompatibility, rich chemical functionalities and well-defined porosity. The unique advantages including metal-free nature and reversible binding manner significantly distinguish HOFs from other porous materials in the biotechnology and biomedical field. However, the relevant HOF studies still remain in their infancy despite the promising and remarkable results that have been presented in recent years. Due to the intricate and dynamic nature of physiological conditions, the major challenge lies in the stability and structural diversity of HOFs in vivo. In this Tutorial Review, we summarize the common building blocks for the construction of HOF-based functional biomaterials and the latest developments in the biological field. Moreover, we highlight current challenges regarding the stability and functionalization of HOFs along with the corresponding potential solutions. This Tutorial Review will have a profound effect in future years on the design and applications of HOF-based biomaterials.

Spin Coherence and Spin Relaxation in Hybrid Organic-Inorganic Lead and Mixed Lead-Tin Perovskites.

Metal halide perovskites make up a promising class of materials for semiconductor spintronics. Here we report a systematic investigation of coherent spin precession, spin dephasing and spin relaxation of electrons and holes in two hybrid organic-inorganic perovskites MA0.3FA0.7PbI3 and MA0.3FA0.7Pb0.5Sn0.5I3 using time-resolved Faraday rotation spectroscopy. With applied in-plane magnetic fields, we observe robust Larmor spin precession of electrons and holes that persists for hundreds of picoseconds. The spin dephasing and relaxation processes are likely to be sensitive to the defect levels. Temperature-dependent measurements give further insights into the spin relaxation channels. The extracted electron Landé g-factors (3.75 and 4.36) are the biggest among the reported values in inorganic or hybrid perovskites. Both the electron and hole g-factors shift dramatically with temperature, which we propose to originate from thermal lattice vibration effects on the band structure. These results lay the foundation for further design and use of lead- and tin-based perovskites for spintronic applications.

Broadband electrically controlled reflective metasurface for reconfigurable circularly polarized wavefront manipulation.

A broadband, electrically controlled, reconfigurable, circularly polarized reflective metasurface is presented. The chirality of the metasurface structure is changed by switching active elements, which benefits from the tunable current distributions generated by the elaborately designed structure under x-polarized and y-polarized waves. Notably, the proposed metasurface unit cell maintains a good circular-polarization efficiency in a broadband range of 6.82-9.96 GHz (fractional bandwidth of 37%) with a phase difference of π between the two states. As a demonstration, a reconfigurable circularly polarized metasurface containing 8 × 8 elements was simulated and measured. The results verify that the proposed metasurface can flexibly control circularly polarized waves in a broadband, realizing beam splitting, mirror reflection, and other beam manipulations from 7.4 GHz to 9.9 GHz (fractional bandwidth of 28.9%) by simply adjusting the loaded active elements. The proposed reconfigurable metasurface may offer a promising approach to electromagnetic wave manipulation or communication systems.

Construction of organic/GaN heterostructures for DUV-to-NIR broadband photodetection.

Herein, a broadband photodetector (BPD) is constructed with consistent and stable detection abilities for deep ultraviolet to near-infrared spectral range. The BPD integrates the GaN template with a hybrid organic semiconductor, PM6:Y6, via the spin-coating process, and is fabricated in the form of asymmetric metal-semiconductor-metal structure. Under an optimal voltage, the device shows consistent photoresponse within 254 to 850 nm, featuring high responsivity (10 to 60 A/W), photo-to-dark-current ratio over 103, and fast response time. These results show the potential of such organic/GaN heterojunctions as a simple and effective strategy to build BPDs for a reliable photo-sensing application in the future.

Polarization multiplexing metasurface for dual-band achromatic focusing.

We propose a dual-band achromatic focusing metasurface based on polarization multiplexing and dispersion engineering. An anisotropic resonant phase meta-atom is designed to realize independent nonlinear phase manipulation along the orthogonal directions. Achromatic focusing metasurface and broadband reflectarray antenna are further constructed in the microwave region with a computer-assisted particle swarm optimization algorithm. The standard deviation of focus offset at 11-16 GHz (for x-polarization) and 18-24 GHz (for y-polarization) are compressed to 19.83% and 16.60% of the dispersive metasurface, respectively. The radiation gains of the reflectarray antenna increase by an average of 19.49 dB and 15.08 dB in the broadband region compared with the bare standard rectangle waveguides. Furthermore, such an achromatic metasurface can be utilized to realize different functions with polarization selectivity and applied to other frequency ranges, which holds great promise in integrated optics.

Full-space beam scanning based on transmission reflection switchable quadratic phase metasurface.

Beam scanning based on metasurfaces is widely discussed in recent years owing to its high integration, lightweight, and low cost. However, most of the reported beam scanning metasurfaces operate in either transmission or reflection mode. Here, we propose a full-space beam scanning metasurface based on transmission reflection switchable meta-atom and the quadratic phase distribution. As a validation, a metasurface array with 400 units (20 × 20) was experimentally demonstrated. Beam scanning of ± 35 ° was achieved in both transmission mode and reflection mode. A larger scanning angle (± 45 °) was further verified simulatively with a 900-units (30 × 30) array. The method provides an avenue for expanding the space of electromagnetic wave manipulation and may have great potential in wireless communication and radar detection.

Design of Synchronization Tracking Adaptive Control for Bilateral Teleoperation System with Time-Varying Delays.

The performances of position synchronization and force interaction of the teleoperation system provide a safe and efficient way for operators to perform tasks in remote, hazardous environments. In practice, however, communication delays and dynamic uncertainties can impair the performance of position synchronization controls. Under the above factors, it is necessary to study and design appropriate bilateral control methods to achieve stable and effective position synchronization control. In this paper, a new adaptive control architecture based on velocity feedback filter and radial basis function neural network is proposed. In the proposed control scheme, only the position signal is transmitted during the communication process, and the speed feedback filter and compensation method are designed and adopted to avoid the use of acceleration signals. In addition, a new auxiliary variable with a tracking error integral term is used to reduce the steady-state error of position tracking under nonzero external environmental forces. Using the Lyapunov-Krasovskii method, the stability of closed-loop remote operating systems is demonstrated. In the simulation and experiment sections, the algorithm was verified separately and compared with other algorithms. The results of a master-slave robot system verify the tracking performance of our proposed control scheme.

Pt/AlGaN Nanoarchitecture: Toward High Responsivity, Self-Powered Ultraviolet-Sensitive Photodetection.

Energy-saving photodetectors are the key components in future photonic systems. Particularly, self-powered photoelectrochemical-type photodetectors (PEC-PDs), which depart completely from the classical solid-state junction device, have lately intrigued intensive interest to meet next-generation power-independent and environment-sensitive photodetection. Herein, we construct, for the first time, solar-blind PEC PDs based on self-assembled AlGaN nanostructures on silicon. Importantly, with the proper surface platinum (Pt) decoration, a significant boost of photon responsivity by more than an order of magnitude was achieved in the newly built Pt/AlGaN nanoarchitectures, demonstrating strikingly high responsivity of 45 mA/W and record fast response/recovery time of 47/20 ms without external power source. Such high solar-blind photodetection originates from the unparalleled material quality, fast interfacial kinetics, as well as high carrier separation efficiency which suggests that embracement of defect-free wide-bandgap semiconductor nanostructures with appropriate surface decoration offers an unprecedented opportunity for designing future energy-efficient and large-scale optoelectronic systems on a silicon platform.

Site-Directed Chemical Modification of Amyloid by Polyoxometalates for Inhibition of Protein Misfolding and Aggregation.

Post-translational modification (PTM) of protein can significantly change protein conformation and function. Inspired by the natural PTM, we present a new approach to inhibit amyloid aggregation by chemical PTM modification. Polyoxometalates (POMs) were used as examples of inhibitors of ß-amyloid peptide (Aß) aggregation to illustrate the chemical PTM method. After the POMs were modified with thiazolidinethione (TZ), the resulting POMD-TZ acted as a chemical PTM agent and could covalently modify Aß site-selectively at Lys16. Multiple biophysical techniques and biochemical assays have been employed to show the superiority of the chemical PTM method compared to traditional Aß inhibitors. Since Aß oligomers are more cytotoxic, we further functionalized POMD-TZ with an Aß-targeted peptide and a fluorescent probe to obtain an "Aß oligomer sensitive" probe. The use of PTM agents for the site-directed chemical modification of proteins provides a new way to regulate amyloid aggregation.

Hydrogen-Bonded Organic Framework (HOF)-Based Single-Neural Stem Cell Encapsulation and Transplantation to Remodel Impaired Neural Networks.

Herein we present a new way to encapsulate neural stem cells (NSCs) by using hydrogen-bonded organic frameworks (HOFs) to overcome the common causes of low therapeutic efficacy during NSC transplantation: 1) loss of fundamental stem cell properties, "stemness", before transplantation, 2) cytomembrane damage during transplantation, and 3) apoptosis due to oxidative stress after transplantation. Porous carbon nanospheres (PCNs) are doped into the HOF shell during the process of mineralization to endow the cellular exoskeletons with hierarchical hydrogen bonds, and the ability to resist oxidative stress due to the catalase and superoxide dismutase-like activities of PCN. Under NIR-II irradiation, thermal-responsive hydrogen bonds dissociate to release NSCs. Stereotactic transplanting encapsulated NSC into the brain of an Alzheimer's disease (AD) mouse model further verifies that our design can enhance NSC viability, promote neurogenesis, and ameliorate cognitive impairment. As the first example of using HOFs to encapsulate NSCs, this work may inspire the design of HOF-based exoskeletons to ameliorate neurogenesis and cognitive behavioral symptoms associated with AD.

NIR-II Hydrogen-Bonded Organic Frameworks (HOFs) Used for Target-Specific Amyloid-ß Photooxygenation in an Alzheimer's Disease Model.

Phototherapy has emerged as a powerful approach for interrupting ß-amyloid (Aß) self-assembly. However, deeper tissue penetration and safer photosensitizers are urgent to be exploited for avoiding damaging nearby normal tissues and improving therapeutic effectiveness. A hydrogen-bonded organic framework (HOF)-based NIR-II photooxygenation catalyst is presented here to settle the abovementioned challenges. By encapsulating the pyridinium hemicyanine dye DSM with a large two-photon absorption (TPA) cross-section in NIR-II window into the porphyrin-based HOF, the resultant DSM@n-HOF-6 exhibits significant two-photon NIR-II-excited Fluorescence Resonance Energy Transfer (FRET) to generate singlet oxygen (1 O2 ) for Aß oxidation. Further, the target peptides of KLVFFAED (KD8) are covalently grafted on DSM@n-HOF-6 to enhance the blood-brain barrier (BBB) permeability and Aß selectivity. The HOF-based photooxygenation catalyst shows an outstanding inhibitory effect of Aß aggregation upon the NIR-II irradiation. Further in vivo studies demonstrate the obvious decrease of craniocerebral Aß plaques and recovery of memory deficits in triple-transgenic AD (3×Tg-AD) model mice.

C-C Coupling Is Unlikely to Be the Rate-Determining Step in the Formation of C2+ Products in the Copper-Catalyzed Electrochemical Reduction of CO.

The identity of the rate-determining step (RDS) in the electrochemical CO reduction reaction (CORR) on Cu catalysts remains unresolved because: 1) the presence of mass transport limitation of CO; and 2) the absence of quantitative correlation between CO partial pressure (pCO ) and surface CO coverage. In this work, we determined CO adsorption isotherms on Cu in a broad pH range of 7.2-12.9. Together with electrokinetic data, we demonstrate that the reaction orders of adsorbed CO at pCO <0.4 and >0.6 atm are 1st and 0th , respectively, for multi-carbon (C2+ ) products on three Cu catalysts. These results indicate that the C-C coupling is unlikely to be the RDS in the formation of C2+ products in the CORR. We propose that the hydrogenation of CO with adsorbed water is the RDS, and the site competition between CO and water leads to the observed transition of the CO reaction order.

Selective Activation of Propane Using Intermediates Generated during Water Oxidation.

Electrochemical conversion of light alkanes to high-value oxygenates provides an attractive avenue for eco-friendly utilization of these hydrocarbons. However, such conversion under ambient conditions remains exceptionally challenging due to the high energy barrier of C-H bond cleavage. Herein, we investigated theoretically the partial oxidation of propane on a series of single atom alloys by using active intermediates generated during water oxidation as the oxidant. We show that by controlling the potential and pH, stable surface oxygen atoms can be maintained under water oxidation conditions. The free energy barrier for C-H bond cleavage by the surface oxygen can be as small as 0.54 eV, which can be surmounted easily at room temperature. Our calculations identified three promising surfaces as effective propane oxidation catalysts. Our complementary experiments demonstrated the partial oxidation of propane to acetone on Ni-doped Au surfaces. We also investigated computationally the steps leading to acetone formation. These studies show that the concept of exploiting intermediates generated in water oxidation as oxidants provides a fruitful strategy for electrocatalyst design to efficiently convert hydrocarbons into value-added chemicals.

Compositionally graded III-nitride alloys: building blocks for efficient ultraviolet optoelectronics and power electronics.

Wide bandgap aluminum gallium nitride (AlGaN) semiconductor alloys have established themselves as the key materials for building ultraviolet (UV) optoelectronic and power electronic devices. However, further improvements to device performance are lagging, largely due to the difficulties in precisely controlling carrier behavior, both carrier generation and carrier transport, within AlGaN-based devices. Fortunately, it has been discovered that instead of using AlGaN layers with fixed Al compositions, by grading the Al composition along the growth direction, it is possible to (1) generate high-density electrons and holes via polarization-induced doping; (2) manipulate carrier transport behavior via energy band modulation, also known as 'band engineering'. Consequently, such compositionally graded AlGaN alloys have attracted extensive interest as promising building blocks for efficient AlGaN-based UV light emitters and power electronic devices. In this review, we focus on the unique physical properties of graded AlGaN alloys and highlight the key roles that such graded structures play in device exploration. Firstly, we elaborate on the underlying mechanisms of efficient carrier generation and transport manipulation enabled by graded AlGaN alloys. Thereafter, we comprehensively summarize and discuss the recent progress in UV light emitters and power electronic devices incorporating graded AlGaN structures. Finally, we outline the prospects associated with the implementation of graded AlGaN alloys in the pursuit of high-performance optoelectronic and power electronic devices.

AlGaN-based deep ultraviolet micro-LED emitting at 275 nm.

The investigation of electrical and optical properties of micro-scale AlGaN deep ultraviolet (DUV) light-emitting diodes (LEDs) emitting at ∼275nm was carried out, with an emphasis on fabricated devices having a diameter of 300, 200, 100, 50, and 20 µm, respectively. It was revealed that the LED chips with smaller mesa areas deliver considerably higher light output power density; meanwhile, they can sustain a higher current density, which is mainly attributed to the enhanced current spreading uniformity in micro-scale chips. Importantly, when the diameter of LED chips decreases from 300 µm to 20 µm, the peak external quantum efficiency (EQE) increases by 20%, and the EQE peak current density can be boosted from 8.85A/cm2 and 99.52A/cm2. Moreover, we observed a longer wavelength emission with enlarged full-width at half-maximum (FWHM) in the LEDs with smaller chip sizes because of the self-heating effect at high current injection. These experimental observations provide insights into the design and fabrication of high-efficiency micro-LEDs emitting in the DUV regime with different device geometries for various future applications.

Enhanced light extraction of the deep-ultraviolet micro-LED via rational design of chip sidewall.

In this Letter, we perform a comprehensive investigation on the optical characterization of micro-sized deep-ultraviolet (DUV) LEDs (micro-LEDs) emitting below 280 nm, highlighting the light extraction behavior in relation to the design of chip sidewall angle. We found that the micro-LEDs with a smaller inclined chip sidewall angle (∼33∘) have improved external quantum efficiency (EQE) performance 19% more than that of the micro-LEDs with a larger angle (∼75∘). Most importantly, the EQE improvement by adopting an inclined sidewall can be more outstanding as the diameter of the LED chip reduces from 40 to 20 µm. The enhanced EQE of the micro-LEDs with smaller inclined chip sidewall angles can be attributed to the stronger reflection of the inclined sidewall, leading to enhanced light extraction efficiency (LEE). In the end, the numerical optical modeling further reveals and verifies the impact of the sidewall angles on the LEE of the micro-LEDs, corroborating our experiment results. This Letter provides a fundamental understanding of the light extraction behavior with optimized chip geometry to design and fabricate highly efficient micro-LEDs in a DUV spectrum of the future.

Development of highly efficient ultraviolet LEDs on hybrid patterned sapphire substrates.

A hybrid patterned sapphire substrate (HPSS) aiming to achieve high-quality Al(Ga)N epilayers for the development of GaN-based ultraviolet light-emitting diodes (UV LEDs) has been prepared. The high-resolution X-ray diffraction measurements reveal that the Al(Ga)N epilayers grown on a HPSS and conventional patterned sapphire substrate (CPSS) have similar structural quality. More importantly, benefiting from the larger refractive index contrast between the patterned silica array and sapphire, the photons can escape from the hybrid substrate with an improved transmittance in the UV band. As a result, in comparison with the UV LEDs grown on the CPSS, the LEDs grown on the HPSS exhibit a significantly enhanced light output power by 14.5% and more than 22.9% higher peak external quantum efficiency, owing to the boost of the light extraction efficiency from the adoption of the HPSS which can be used as a promising substrate to realize high-efficiency and high-power UV LEDs of the future.

Efficient Degradation of Organoarsenic by UV/Chlorine Treatment: Kinetics, Mechanism, Enhanced Arsenic Removal, and Cytotoxicity.

Roxarsone (ROX) has been widely used as an organoarsenic additive in animal feeding operations and poses a risk to the environment. Here, we first report the efficient degradation of ROX by UV/chlorine, where the kinetics, removal of total arsenic (As), and cytotoxicity were investigated. The kinetics study presented that reactive chlorine species (RCS) and HO• were the dominant species to react with ROX. Furthermore, the degradation rate of ROX can reach the maximum value at pH 7.5 due to the formation of more RCS. The degradation of ROX was affected by the amount of chlorine, pH, and water matrix. Through product analysis and Gauss theoretical calculation, two possible ROX degradation pathways were proposed. The free radicals attacked the As-C bond of ROX and resulted in releasing arsenate (As(V)). It was the reason that for an enhancement of the removal of total As by ferrous appeared after UV/chlorine, and over 98% of the total As was removed. In addition, cytotoxicity studies indicated that the cytotoxicity significantly enhanced during the degradation of ROX by UV/chlorine. However, by combination of UV/chlorine and adsorption, cytotoxicity can be greatly eliminated, probably due to the removal of As(V) and chlorinated products. These results further demonstrated that UV/chlorine treatment could be an effective method for the control of the potential environmental risks posed by organoarsenic.