Nanomedicines Targeting Ferroptosis to Treat Stress-Related Diseases.

Ferroptosis, a unique form of regulated cell death driven by iron-dependent lethal lipid peroxidation, is implicated in various stress-related diseases like neurodegeneration, vasculopathy, and metabolic disturbance. Stress-related diseases encompass widespread medical disorders that are influenced or exacerbated by stress. These stressors can manifest in various organ or tissue systems and have significant implications for human overall health. Understanding ferroptosis in these diseases offers insights for therapeutic strategies targeting relevant pathways. This review explores ferroptosis mechanisms, its role in pathophysiology, its connection to stress-related diseases, and the potential of ferroptosis-targeted nanomedicines in treating conditions. This monograph also delves into the engineering of ferroptosis-targeted nanomedicines for tackling stress-related diseases, including cancer, cardia-cerebrovascular, neurodegenerative, metabolic and inflammatory diseases. Anyhow, nanotherapy targeting ferroptosis holds promise by both promoting and suppressing ferroptosis for managing stress-related diseases.

Revealing Roles of High-Electronegativity Fluorine Atoms in Boosting Redox Potential of Layered Sodium Cathodes.

The development of high-energy-density cathode materials is regarded as the ultimate goal of alkali metal-ion batteries energy storage. However, the strategy of regulating specific capacity is limited by the theoretical capacity, and meanwhile focusing on improving capacity will lead to structural destructions. Herein, a novel perspective is proposed that tuning the electronic band structure by introducing highly electronegative fluoride atoms in NaxTMO2-yFy (0 < x < 1, 0 < y < 2) model compounds to improve redox potential for developing high-energy-density layered oxides. Highly electronegative fluoride atoms is introduced into P2-type Na0.67Fe0.5Mn0.5O2 (NFM), and the thus fluoride NFM (F-NFM) cathode achieved high redox potential (3.0 V) and high energy density (446 Wh kg-1). Proved by structural characterizations, fluorine atoms are successfully incorporated into oxygen sites in NFM lattice. Ultraviolet photoelectron spectroscopy is applied to quantitatively analyze the improved redox potential of F-NFM, which is achieved by the decreased valence band energy in electronic band structure due to the strongly electrophilic fluoride ions. Moreover, fluoride atoms can stabilize the local environment of NFM and improve its redox potential. The work provides a perspective to improve redox potential by tuning the electronic band structure in layered oxides and developing high-energy-density alkali metal-ion batteries.

One-Pot Biocatalytic Conversion of Chemically Inert Hydrocarbons into Chiral Amino Acids through Internal Cofactor and H2O2 Recycling.

Chemically inert hydrocarbons are the primary feedstocks used in the petrochemical industry and can be converted into more intricate and valuable chemicals. However, two major challenges impede this conversion process: selective activation of C-H bonds in hydrocarbons and systematic functionalization required to synthesize complex structures. To address these issues, we developed a multi-enzyme cascade conversion system based on internal cofactor and H2O2 recycling to achieve the one-pot deep conversion from heptane to chiral (S)-2-aminoheptanoic acid under mild conditions. First, a hydrogen-borrowing-cycle-based NADH regeneration method and H2O2in situ generation and consumption strategy were applied to realize selective C-H bond oxyfunctionalization, converting heptane into 2-hydroxyheptanoic acid. Integrating subsequent reductive amination driven by the second hydrogen-borrowing cycle, (S)-2-aminoheptanoic acid was finally accumulated at 4.57 mM with eep > 99%. Hexane, octane, 2-methylheptane, and butylbenzene were also successfully converted into the corresponding chiral amino acids with eep > 99%. Overall, the conversion system employed internal cofactor and H2O2 recycling, with O2 as the oxidant and ammonium as the amination reagent to fulfill the enzymatic conversion from chemically inert hydrocarbons into chiral amino acids under environmentally friendly conditions, which is a highly challenging transformation in traditional organic synthesis.

Excitonic van der Waals Metasurfaces for Resonant Wavefront Shaping at Deep Subwavelength Thickness Scale.

Dielectric phase gradient metasurfaces have emerged as promising candidates to shrink bulky optical elements to subwavelength thickness scale based on dielectric meta-atoms. These meta-atoms strongly interact with light, thus offering excellent phase manipulation of incident light. However, to fulfill 2π phase control using meta-atoms, the metasurface thickness, to date, is limited to the order of 102 nm. Here, we present the thickness scaling down of phase gradient metasurfaces to <λ/20 by using excitonic van der Waals metasurfaces. High-refractive-index enabled by exciton resonances and symmetry-breaking nanostructures in the patterned layered tungsten disulfide (WS2) corporately enable quasibound states in the continuum in WS2 metasurfaces, which consequently yield complete phase regulation of 2π with the thickness down to 35 nm. To illustrate the concept, we have experimentally demonstrated beam steering, focusing, and holographic display using WS2 metasurfaces. We envision our results unveiling new venues for ultimate thin phase gradient metasurfaces.

Epitaxy of Monoclinic VO2 on Large-Misfit 3m Template Enabled by a Metastable Interfacial Layer.

We report the epitaxial growth of a monoclinic VO2 thin film on the CoFe2O4(111) template, assisted by an interfacial layer of the metastable orthorhombic phase. The interface between orthorhombic VO2 and CoFe2O4 is atomically sharp without noticeable interfacial diffusion. The (010)-faceted orthorhombic VO2 layer is lattice-matched to both the CoFe2O4(111) template and the monoclinic phase, although they have different surface symmetries. The occurrence of an orthorhombic VO2 thin layer significantly lowers the in-plane misfit strains of the monoclinic VO2 epilayer, along both the [100] and [001] axes. Our first-principles calculations confirm that the low-misfit orthorhombic VO2 is preferred on CoFe2O4(111) over the large-misfit monoclinic phase, at the initial growth stage. Additionally, upon increasing the film thickness to ∼8 nm, the orthorhombic phase is no longer favored, and the bulk stable monoclinic VO2 appears to minimize the free energy of the system. Moreover, we show that the metal-to-insulator transition of our VO2 epilayer can be efficiently triggered by both the temperature and Joule self-heating effect.

Spin-Locked WS2 Vortex Emission via Photonic Crystal Bound States in the Continuum.

Owing to their strong exciton effects and valley polarization properties, monolayer transition-metal dichalcogenides (1L TMDs) have unfolded the prospects of spin-polarized light-emitting devices. However, the wavefront control of exciton emission, which is critical to generate structured optical fields, remains elusive. In this work, the experimental demonstration of spin-locked vortex emission from monolayer Tungsten Disulfide (1L WS2) integrated with Silicon Nitride (SiNx) PhC slabs is presented. The symmetry-protected bound states in the continuum (BIC) in the SiNx PhC slabs engender azimuthal polarization field distribution in the momentum space with a topological singularity in the center of the Brillouin zone, which imposes the resonantly enhanced WS2 exciton emission with a spin-correlated spiral phase front by taking advantage of the winding topologies of resonances with the assistance of geometric phase scheme. As a result, exciton emission from 1L WS2 exhibits helical wavefront and doughnut-shaped intensity beam profile in the momentum space with topological charges locked to the spins of light. This strategy on spin-dependent excitonic vortex emission may offer the unparalleled capability of valley-polarized structured light generation for 1L TMDs.

Chiral absorption enhancement via critically coupled resonances in atomically thin photonic crystal exciton-polaritons.

Atomically thin transition metal dichalcogenides (TMDS) offer a promising route to the scaling down of optoelectronic devices to the ultimate thickness limit. But the weak light-matter interaction caused by their atomically thin nature makes them inevitably rely on external photonic structures to enhance optical absorption. Here, we report chiral absorption enhancement in atomically thin tungsten diselenide (WSe2) using chiral resonances in photonic crystal (PhC) nanostructures patterned directly in WSe2 itself. We show that the quality factors (Q factors) of the resonances grow exponentially as the PhC thickness approaches atomic limit. As such, the strong interaction of high Q factor photonic resonance with the coexisting exciton resonance in WSe2 results into self-coupled exciton-polaritons. By balancing the light coupling and absorption rates, the incident light can critically couple to chiral resonances in WSe2 PhC exciton-polaritons, leading to the theoretically limited 50% optical absorptance with over 84% circular dichroism (CD).

Electronic and Transport Properties of InSe/PtTe2 van der Waals Heterostructure.

Two-dimensional (2D) InSe and PtTe2 have drawn extensive attention due to their intriguing properties. However, the InSe monolayer is an indirect bandgap semiconductor with a low hole mobility. van der Waals (vdW) heterostructures produce interesting electronic and optoelectronic properties beyond the existing 2D materials and endow totally new device functions. Herein, we theoretically investigated the electronic structures, transport behaviors, and electric field tuning effects of the InSe/PtTe2 vdW heterostructures. The calculated results show that the direct bandgap type-II vdW heterostructures can be realized by regulating the stacking configurations of heterostructures. By applying an external electric field, the band alignment and bandgap of the heterostructures can also be flexibly modulated. Particularly, the hole mobility of the heterostructures is improved by 2 orders of magnitude to ∼103 cm2 V-1 s-1, which overcomes the intrinsic disadvantage of the InSe monolayer. The InSe/PtTe2 vdW heterostructures have great potential applications in developing novel optoelectronic devices.

Efficient pure-red perovskite light-emitting diodes with strong passivation via ultrasmall-sized molecules.

Perovskite light-emitting diodes (PeLEDs) have attracted great attention in recent years; however, the halogen vacancy defects in perovskite notably hamper the development of high-efficiency devices. Previously, large-sized passivation agents have been usually used, while the effect of defect passivation is limited due to the weak bonding or the large space steric hindrance. Here, we predict that the ultrasmall-sized formate (Fa) and acetate (Ac) have more efficient passivation ability because of the stronger binding with the perovskite, as demonstrated by density functional theory calculation. We introduce ultrasmall-sized cesium salts (CsFa/CsAc) into buried interface, which can also diffuse into the bulk, resulting in both buried interface and bulk passivation. In addition, the improved perovskite growth has been found due to the enhanced hydrophily after introducing CsFa/CsAc as additive. According to these advantages, a pure-red PeLED with 24.2% efficiency at 639 nm has been achieved.

Transport and Spatial Separation of Valley Coherence via Few Layer WS2 Exciton-Polaritons.

The optical response in two-dimensional transition-metal dichalcogenides (2D TMDCs) is dominated by excitons. The lack of spatial inversion symmetry in the hexagonal lattice within each TMDC layer leads to valley-dependent excitonic emission of photoluminescence. Here, we demonstrate experimentally the spatial separation of valley coherent emission into orthogonal directions through self-resonant exciton polaritons of a free-standing three-layer (3L) WS2 waveguide. This was achieved by patterning a photonic crystal consisting of a square array of holes allowing for the far field probing of valley coherence of engendered exciton-polaritons. Furthermore, we report detailed experimental modal characterization of this coupled system in good agreement with theory. Momentum space measurements reveal a degree of valley coherence in the range 30-60%. This work provides a platform for manipulation of valley excitons in coherent light-matter states for potential implementations of valley-coherent optoelectronics.

Single-Photon Emission from Point Defects in Hexagonal Boron Nitride Induced by Plasma Treatment.

Solid-state quantum emitters are gaining significant attention for many quantum information applications. Hexagonal boron nitride (h-BN) is an emerging host material for generating bright, stable, and tunable single-photon emission with narrow line widths at room temperature. In this work, we present a facile and efficient approach to generate high-density single-photon emitters (SPEs) in mechanically exfoliated h-BN through H- or Ar-plasma treatment followed by high-temperature annealing in air. It is notable that the postannealing is essential to suppress the fluorescence background in photoluminescence spectra and enhance emitter stability. These quantum emitters exhibit excellent optical properties, including high purity, brightness, stability, polarization degree, monochromaticity, and saturation intensity. The effects of process parameters on the quality of quantum emitters were systematic investigated. We find that there exists an optimal plasma power and h-BN thickness to achieve a high SPE density. This work offers a practical avenue for generating SPEs in h-BN and holds promise for future research and applications in quantum photonics.

IMD-Net: Interpretable multi-scale detection network for infrared dim and small objects.

This study proposed an interpretable multi-scale infrared small object detection network (IMD-Net) design method to improve the precision of infrared small object detection and contour segmentation in complex backgrounds. To this end, a multi-scale object enhancement module was constructed, which converted artificially designed features into network structures. The network structure was used to enhance actual objects and extract shallow detail and deep semantic features of images. Next, a global object response, channel attention, and multilayer feature fusion modules were introduced, combining context and channel information and aggregated information, selected data, and decoded objects. Finally, the multiple loss constraint module was constructed, which effectively constrained the network output using multiple losses and solved the problems of high false alarms and high missed detections. Experimental results showed that the proposed network model outperformed local energy factor (LEF), self-regularized weighted sparse model (SRWS), asymmetric contextual modulation (ACM), and other state of the art methods in the intersection-over-union (IoU) and Fmeasure values by 10.8% and 11.3%, respectively. The proposed method performed best on the currently available datasets, achieving accurate detection and effective segmentation of dim and small objects in various infrared complex background images.

All-optical geometric image transformations enabled by ultrathin metasurfaces.

Image processing plays a vital role in artificial visual systems, which have diverse applications in areas such as biomedical imaging and machine vision. In particular, optical analog image processing is of great interest because of its parallel processing capability and low power consumption. Here, we present ultra-compact metasurfaces performing all-optical geometric image transformations, which are essential for image processing to correct image distortions, create special image effects, and morph one image into another. We show that our metasurfaces can realize binary image transformations by modifying the spatial relationship between pixels and converting binary images from Cartesian to log-polar coordinates with unparalleled advantages for scale- and rotation-invariant image preprocessing. Furthermore, we extend our approach to grayscale image transformations and convert an image with Gaussian intensity profile into another image with flat-top intensity profile. Our technique will potentially unlock new opportunities for various applications such as target tracking and laser manufacturing.

Biosynthesis of 4-Acyl-5-aminoimidazole Alkaloids Featuring a New Friedel-Crafts Acyltransferase.

Friedel-Crafts acylation (FCA) is a highly beneficial approach in organic chemistry for creating the important C-C bonds that are necessary for building intricate frameworks between aromatic substrates and an acyl group. However, there are few reports about enzyme catalyzed FCA reactions. In this study, 4-acyl-5-aminoimidazole alkaloids (AAIAs), streptimidazoles A-C (1-3), and the enantiopure (+)-nocarimidazole C (4) as well as their ribosides, streptimidazolesides A-D (5-8), were identified from the fermentation broth of Streptomyces sp. OUCMDZ-944 or heterologous S. coelicolor M1154 mutant. The biosynthetic gene cluster (smz) was identified, and the biosynthetic pathway of AAIAs was elucidated for the first time. In vivo and in vitro studies proved the catalytic activity of the four essential genes smzB, -C, -E, and -F for AAIAs biosynthesis and clarified the biosynthetic process of the alkaloids. The ligase SmzE activates fatty acyl groups and connects them to the acyl carrier protein (ACP) holo-SmzF. Then, the acyl group is transferred onto the key residue Cys49 of SmzB, a new Friedel-Crafts acyltransferase (FCase). Subsequently, the FCA reaction between the acyl groups and 5-aminoimidazole ribonucleotide (AIR) occurs to generate the key intermediate AAIA-nucleotides catalyzed by SmzB. Finally, the hydrolase SmzC catalyzes the N-glycosidic bond cleavage of the intermediates to form AAIAs. Structural simulation, molecular modeling, and mutational analysis of SmzB showed that Tyr26, Cys49, and Tyr93 are the key catalytic residues in the C-C bond formation of the acyl chain of AAIAs, providing mechanistic insights into the enzymatic FCA reaction.

Integrated Network Pharmacology and Cellular Assay to Explore the Mechanisms of Selenized Tripterine Phytosomes (Se@Tri-PTs) Alleviating Podocyte Injury in Diabetic Nephropathy.

AIM: This work aimed to elucidate the mechanisms of Se@Tri-PTs in alleviating podocyte injury via network pharmacology and in vitro cellular assay. BACKGROUND: Selenized tripterine phytosomes (Se@Tri-PTs) have been confirmed to undertake synergistic and sensitized effects on inflammation, which may be curatively promising for diabetic nephropathy (DN). However, the mechanisms of Se@Tri-PTs in alleviating podocyte injury, a major contributor to DN, still remain unclear. OBJECTIVE: The objective of the study was to find out the underlying mechanisms of Se@Tri-PTs in alleviating podocyte injury in diabetic nephropathy. METHODS: The key components and targets of Tripterygium wilfordii (TW) significant for DN as well as the signaling pathways involved have been identified. A high glucose-induced podocyte injury model was established and verified by western blot. The protective concentration of Se@Tri-PTs was screened by CCK-8 assay. Podocytes cultured with high glucose were treated with Se@Tri-PTs under protective levels. The expression of key protective proteins, nephrin and desmin, in podocytes, was assayed by western blot. Further, autophagy- related proteins and factors, like NLRP3, Beclin-1, LC3II/LC3, P62, and SIRT1, were analyzed, which was followed by apoptosis detection. RESULTS: Network pharmacology revealed that several monomeric components of TW, especially Tri, act on DN through multiple targets and pathways, including the NLRP3-mediated inflammatory pathway. Se@Tri-PTs improved the viability of podocytes and alleviated their injury induced by high glucose at 5 µg/L or above. High-glucose induction promoted the expression of NLRP3 in podocytes, while a low concentration of Se@Tri-PTs suppressed the expression. A long-term exposure of high glucose significantly inhibited the autophagic activity of podocytes, as manifested by decreased Beclin-1 level, lower ratio of LC3 II/LC3 I, and up- regulation of P62. This abnormality was efficiently reversed by Se@Tri-PTs. Importantly, the expression of SIRT1 was up-regulated and podocyte apoptosis was reduced. CONCLUSION: Se@Tri-PTs can alleviate podocyte injury associated with DN by modulating NLRP3 expression through the pathway of SIRT1-mediated autophagy.

Homogenized NiOx nanoparticles for improved hole transport in inverted perovskite solar cells.

The power conversion efficiency (PCE) of inverted perovskite solar cells (PSCs) is still lagging behind that of conventional PSCs, in part because of inefficient carrier transport and poor morphology of hole transport layers (HTLs). We optimized self-assembly of [4-(3,6-dimethyl-9H-carbazol-9-yl)butyl]phosphonic acid (Me-4PACz) onto nickel oxide (NiOx) nanoparticles as an HTL through treatment with hydrogen peroxide, which created a more uniform dispersion of nanoparticles with high conductivity attributed to the formation of Ni3+ as well as surface hydroxyl groups for bonding. A 25.2% certified PCE for a mask size of 0.074 square centimeters was obtained. This device maintained 85.4% of the initial PCE after 1000 hours of stabilized power output operation under 1 sun light irradiation at about 50°C and 85.1% of the initial PCE after 500 hours of accelerated aging at 85°C. We obtained a PCE of 21.0% for a minimodule with an aperture area of 14.65 square centimeters.

Nanomedicines based on trace elements for intervention of diabetes mellitus.

Epidemiology shows that the incidence of diabetes mellitus (DM) is increasing year by year globally. Proper interventions are highly aspired for diabetics to improve the quality of life and prevent development of chronic complications. Trace elements, also known as microelements, are chemical substances that are present in our body in minute amounts. They are necessitated by the body for growth, development and functional metabolism. For the past few years, trace element nanoparticles have aroused considerable interest as a burgeoning form of nanomedicines in antidiabetic applications. These microelement-based nanomedicines can regulate glucose metabolism in several ways, showing great potential for diabetes management. Starting from the pathophysiology of diabetes, the state-of-the-art of diabetes treatment, the physiological roles of trace elements, various emerging trace element nanoparticles specific for diabetes were comprehensively reviewed in this work. Our findings disclose that trace element nanoparticles can fight against diabetes by lowering blood glucose, promoting insulin secretion, alleviating glucose intolerance, improving insulin sensitivity, ameliorating lipid profile, anti-inflammation and anti-oxidant stress, and other mechanisms. In conclusion, trace element nanoparticles can be applied as nanomedicines or dietary modifiers for effective intervention for diabetes.

Drug Delivery and Therapy Strategies for Osteoporosis Intervention.

With the advent of the aging society, osteoporosis (OP) risk increases yearly. Currently, the clinical usage of anti-OP drugs is challenged by recurrent side effects and poor patient compliance, regardless of oral, intravenous, or subcutaneous administration. Properly using a drug delivery system or formulation strategy can achieve targeted drug delivery to the bone, diminish side effects, improve bioavailability, and prolong the in vivo residence time, thus effectively curing osteoporosis. This review expounds on the pathogenesis of OP and the clinical medicaments used for OP intervention, proposes the design approach for anti-OP drug delivery, emphatically discusses emerging novel anti-OP drug delivery systems, and enumerates anti-OP preparations under clinical investigation. Our findings may contribute to engineering anti-OP drug delivery and OP-targeting therapy.

The feasibility of oral targeted drug delivery: Gut immune to particulates?

Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration (oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake.

Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase.

Diterpene synthase VenA is responsible for assembling venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. VenA also demonstrates substrate promiscuity by accepting geranyl pyrophosphate and farnesyl pyrophosphate as alternative substrates. Herein, we report the crystal structures of VenA in both apo form and holo form in complex with a trinuclear magnesium cluster and pyrophosphate group. Functional and structural investigations on the atypical 115DSFVSD120 motif of VenA, versus the canonical Asp-rich motif of DDXX(X)D/E, reveal that the absent second Asp of canonical motif is functionally replaced by Ser116 and Gln83, together with bioinformatics analysis identifying a hidden subclass of type I microbial terpene synthases. Further structural analysis, multiscale computational simulations, and structure-directed mutagenesis provide significant mechanistic insights into the substrate selectivity and catalytic promiscuity of VenA. Finally, VenA is semi-rationally engineered into a sesterterpene synthase to recognize the larger substrate geranylfarnesyl pyrophosphate.