Enhancing anti-angiogenic immunotherapy for melanoma through injectable metal-organic framework hydrogel co-delivery of combretastatin A4 and poly(I:C).

The interplay between vascularization and macrophage-induced immune suppression plays a crucial role in melanoma treatment. In this study, we propose a novel combination approach to combat melanoma by simultaneously inhibiting tumor vascularization and enhancing macrophage-mediated anti-tumor responses. We investigate the potential of combining combretastatin A4 (CA4), a vascular-disrupting agent, with poly(I:C) (PIC), an immunostimulatory adjuvant. This combination approach effectively suppresses melanoma cell proliferation, disrupts vascularization, and promotes macrophage polarization towards the M1 phenotype for melanoma suppression. To facilitate efficient co-delivery of CA4 and PIC for enhanced anti-angiogenic immunotherapy, we develop an injectable metal-organic framework hydrogel using Zeolitic Imidazolate Framework-8 (ZIF-8) and hyaluronic acid (HA) (ZIF-8/HA). Our findings demonstrate that ZIF-8 enables efficient loading of CA4 and enhances the stability of PIC against RNAase degradation in vitro. Furthermore, the developed co-delivery hydrogel system, PIC/CA4@ZIF-8/HA, exhibits improved rheological properties, good injectability and prolonged drug retention. Importantly, in vivo experiments demonstrate that the PIC/CA4@ZIF-8/HA formulation significantly reduces the dosage and administration frequency while achieving a more pronounced therapeutic effect. It effectively inhibits melanoma growth by suppressing angiogenesis, destroying blood vessels, promoting M1 macrophage infiltration, and demonstrating excellent biocompatibility. In conclusion, our study advances anti-angiogenic immunotherapy for melanoma through the potent combination of PIC/CA4, particularly when administered using the PIC/CA4@ZIF-8/HA formulation. These findings provide a new perspective on clinical anti-angiogenic immunotherapy for melanoma, emphasizing the importance of targeting tumor vascularization and macrophage-mediated immune suppression simultaneously.

High-Throughput Multitarget Molecular Detection in an Automatic Light-Addressable Photoelectrochemical Sensing Platform.

Successively emerged high-throughput multitarget molecular detection methods bring significant development tides in chemical, biological, and environmental fields. However, several persistent challenges of intricate sample preparation, expensive instruments, and tedious and skilled operations still need to be further addressed. Here, we propose an automatic light-addressable photoelectrochemical (ALA-PEC) sensing platform for sensitive and selective detection of multitarget molecules. With Au nanoparticle-decorated TiO2 nanotube photonic crystals (Au-TiO2 NTPCs) as a photoelectrode and 8 kinds of antibiotics as target molecules, the ALA-PEC sensing system implements automatic detection of multimolecules in a short time with high sensitivity and good selectivity. Random samples with different amounts of antibiotics have been well-distinguished in the ALA-PEC system, and both the chemical components and concentrations have been well-illustrated in a pattern recognition model. It is worth noting that 8 samples are not the limit of the ALA-PEC sensing platform, which can be easily expanded to more complex detection arrays based on practical needs. The emerging ALA-PEC sensing platform provides a new solution for rapid screening and detection of multitarget and high-throughput substances and potentially brings the automatic, portable, sensitive, high-throughput, and cost-effective detection technique to an entire new realm.

Decitabine suppresses MDSC-induced immunosuppression through dual functional mechanism and inhibits melanoma metastasis.

Myeloid-derived suppressor cells (MDSCs) play a crucial role in promoting melanoma metastasis. Reprogramming MDSCs into mature M1 macrophages has emerged as a strategy to inhibit metastasis. Decitabine (Dec) is known to eradicate MDSCs and suppress tumor growth. In this study, we provide evidence that Dec not only reduces the MDSC population by inducing apoptosis, arresting cell cycle, and impairing recruitment, but also suppresses their immunosuppressive function by downregulating related genes and facilitating differentiation into M1 macrophages. Transcriptomic analysis of Dec-treated MDSCs revealed a marked downregulation of immunosuppressive genes including S100a9, S100a8, Vegf, Cxcr2, and Nos2. Meanwhile, M1 macrophage-associated genes involved in immune activation were upregulated, such as Ddx58, Isg15, Tap1, Ccl5, Cxcl9, and Cxcl10. Further bioinformatic analysis indicated that Dec promotes MDSC-to-M1 macrophage differentiation and activates innate immune pathways including NOD-like signaling to enhance anti-tumor immunity. Time-course studies implied that Dec upregulates myeloid transcription factor Irf7 to initiate MDSC differentiation and orchestrate the anti-tumor immune response. Collectively, our study unveils a novel dual-functional mechanism of Dec as both a cytotoxic agent reducing MDSCs and an inducer of their differentiation into M1 macrophages, thereby alleviating immunosuppression. This highlights Dec's potential for clinical melanoma metastasis suppression.

Hydrogel/MOF Dual-Modified Photoelectrochemical Biosensor for Antibiofouling and Biocompatible Dopamine Detection.

For accurate in vivo detection, nonspecific adsorption of biomacromolecules such as proteins and cells is a severe issue. The adsorption leads to electrode passivation, significantly compromising both the sensitivity and precision of sensing. Meanwhile, common antibiofouling modifications, such as polymer coatings, still grapple with issues related to biocompatibility, electrode passivation, and miniaturization. Herein, we propose a composite antibiofouling coating strategy based on zwitterionic metal-organic frameworks (Z-MOFs) and a combination of acrylamide hydrogels. On a well-designed TiO2/Z-MOF/hydrogel photoelectrode, we achieve highly sensitive and selective detection of dopamine in complex biological environments. The hydrogel's three-dimensional porous structure combined with unique microporous architecture of Z-MOF ensures effective sieving of interfering macromolecules while preserving efficient small molecules and electron transport. This innovative approach paves the way for constructing miniature, in vivo antibiofouling sensors for molecule monitoring in living organisms with complicated chemical environments.

Photonic-plasmonic resonator for SERS biodetection.

To improve the laser utilization efficiency and avoid photodamage in surface-enhanced Raman spectroscopy (SERS), it is imperative to introduce photon technology into the field of SERS detection. A major challenge is the inefficient interaction between the substrate and the incident wavelength, resulting in limited Raman enhancement at a relatively low level. Here, we sputtered plasmonic Au nanoparticles (NPs) onto photonic TiOx nanocavities, creating a novel hybrid photonic-plasmonic resonator that achieves a large degree of optical manipulation and long-term localization. By facilely controlling the size of Au NPs, the resonance wavelength of plasmonic Au NPs can be matched with the photonic nanocavity to maximize the light trapping intensity, which leads to a synergistic enhancement of SERS via the electromagnetic and chemical mechanisms, resulting in a SERS enhancement up to 1.75 × 109 under non-resonant excitation. In particular, the substrate can achieve strong absorption and localization for long wavelengths, thus enabling a large SERS enhancement with a small light intensity, which can effectively avoid the photodamage that may occur in Raman testing. The substrate can detect various biomolecules, including biomarkers in serum, thus realizing the differentiation of different cancers. This study provides a powerful and sensitive platform for SERS, facilitating bioanalysis and disease diagnosis in complex systems.

Highly ordered nanocavity as photonic-plasmonic-polaritonic resonator for single molecule miRNA SERS detection.

Strong light-matter coupling between molecules and electromagnetic field lead to the formation of hybrid polaritonic states for surface enhanced Raman scattering (SERS) detection. However, owing to the inefficient interaction between zero-point fluctuations of photons/plasmons and molecular electronic transitions, the Raman enhancement is limited in relative low levels. Here, we propose and fabricate a TiOx/Cu2-xSe/R6G nanocavity based photonic-plasmonic-polaritonic resonator for single molecular SERS detection. Through precisely matching the energy levels of illuminated photon, generated plasmon, and molecular polariton, an extremely high Raman enhancement factor of 2.6 × 109 is implemented. The rationally designed SERS substrate allows sensitive detection of miRNA-21 in single molecular level with a detection limit of 1.58 aM. The hybrid SERS mechanism both from electromagnetic and chemical perspectives in this photonic-plasmonic-polaritonic resonance strategy provides insight into polaritonic semiconductor systems, thus paving the way for new experimental possibilities in light-matter hybrids.

Oxygen Vacancies-Induced Antifouling Photoelectrochemical Aptasensor for Highly Sensitive and Selective Determination of α-Fetoprotein.

Accurate measurement of cancer markers in urine is a convenient method for tumor monitoring. However, the concentration of cancer markers in urine is so low that it is difficult to achieve their measurement. Photoelectrochemical (PEC) sensors are a promising technology to realize the detection of trace cancer markers due to their high sensitivity. Currently, the interference of nonspecific biomolecules in urine is the main reason affecting the high sensitivity and selectivity of PEC sensors in detecting cancer markers. In this work, a strategy of oxygen vacancy (OV) modulation is proposed to construct a fouling-resistant PEC aptamer sensing platform for the detection of α-fetoprotein (AFP), a liver cancer marker. The introduction of OVs induces the formation of intermediate localized states in the photoelectric material, which not only facilitates the separation of photogenerated carriers but also leads to the redshift of the light absorption edge. More importantly, OVs with positive electrical properties can be employed to modify the antifouling layer (C-PEG) with negatively charged groups through an electrostatic interaction. The synergistic effect of OVs, antifouling layer, and aptamer resulted in a TiO2/OVs/C-PEG-based PEC sensor achieves a wide linear range from 1 pg/mL to 100 ng/mL and a low detection limit of 0.3 pg/mL for AFP. In addition, the sensor successfully realized the determination of AFP in urine samples and accurately differentiated between normal people and liver cancer patients in the early and advanced stages. This project is of great significance in advancing the application of photoelectrochemical bioanalytical technology to achieve the detection of cancer markers in urine by investigating the construction of an OVs-regulated fouling-resistant sensing interface.

Modulation of active center distance of hybrid perovskite for boosting photocatalytic reduction of carbon dioxide to ethylene.

Solar-driven photocatalytic CO2 reduction is an energy-efficient and sustainable strategy to mitigate CO2 levels in the atmosphere. However, efficient and selective conversion of CO2 into multi-carbon products, like C2H4, remains a great challenge due to slow multi-electron-proton transfer and sluggish C-C coupling. Herein, a two-dimensional thin-layered hybrid perovskite is fabricated through filling of oxygen into iodine vacancy in pristine DMASnI3 (DMA = dimethylammonium). The rational-designed DMASnI3(O) induces shrinkage of active sites distance and facilitates dimerization of C-C coupling of intermediates. Upon simulated solar irradiation, the DMASnI3(O) photocatalyst achieves a high selectivity of 74.5%, corresponding to an impressive electron selectivity of 94.6%, for CO2 to C2H4 conversion and an effective C2H4 yield of 11.2 µmol g-1 h-1. In addition, the DMASnI3(O) inherits excellent water stability and implements long-term photocatalytic CO2 reduction to C2H4 in a water medium. This work establishes a unique paradigm to convert CO2 to C2+ hydrocarbons in a perovskite-based photocatalytic system.

Single-Fe-Atom Catalyst for Sensitive Electrochemical Detection of Caffeic Acid.

A single-atom catalyst (Fe SAs/-N-C) with excellent stability and conductivity was strategically fabricated via high-temperature calcination using the NiFe layered double hydroxide (LDH)/ZIF-8 composite as precursors. With the help of Ni as a catalyst, a great number of carbon nanotubes were produced whereby the isolated carbon bulks were interconnected to form an "island-bridge"-like 3D network structure, which greatly enhanced the exposure of active sites and the electron transfer. Accordingly, caffeic acid (CA) with versatile biological and pharmacological activities was chosen as the model analyte. The Fe SAs/-N-C with Fe-N4 as the catalytic active site was employed to establish the electrochemical sensing of CA with satisfactory sensitivity, selectivity, and long-term stability. This work expands the application range of single-atom catalysts and contributes a significant reference for the synthesis of hybrid double-atom catalysts.

Fabrication of near infrared light responsive photoelectrochemical immunosensor for in vivo detection of melanoma cells.

Effective and convenient detection of melanoma cells with high sensitivity is essential to identify malignant melanoma in its early stage. However, the existing detection methods, such as immunohistochemical analysis, are too complicated and time-consuming to realize the convenient in vivo and in situ detection. Herein, a near infrared responsive photoelectrochemical (PEC) immunosensor is proposed with plasmonic Au nanoparticles-photonic TiO2 nanocaves (Au/TiO2 NCs) as photon harvest and conversion transducer and antibody as cell recognition unit. The micro-antibody/Au/TiO2 NCs photoelectrode can easily in vivo distinguish melanoma cells and can realize sensitive detection of melanoma cells in short time of 1 min with a lowest limit of detection of 2 cell mL-1. The PEC immunosensor strategy not only allows us to pioneeringly implement sensitive in vivo bio-detection, but also opens up a new avenue for rational design of cell recognition units and micro-electrode for universal and reliable bio-detections.

Immunologically active ferumoxytol-poly(I : C) nanomaterials inhibit metastatic melanoma by regulating myeloid-derived suppressor cell differentiation.

Nanomaterials have been identified as a potential therapeutic option for targeting myeloid-derived suppressor cells (MDSCs), which are known to play a crucial role in tumor metastasis and treatment resistance. Here, we report a unique immunologically active nanomaterial composed of ferumoxytol and poly(I : C) (FP-NPs) and investigate its immunoregulatory activities on MDSCs in metastatic melanoma. In vivo assays demonstrated that FP-NPs had the ability to significantly impede the progression of metastatic melanoma and decrease the MDSC population in the lungs, spleen, and bone marrow of mice. Both in vivo and in vitro experiments revealed that FP-NPs reduced the number of granulocytic MDSCs and promoted the differentiation of monocytic MDSCs into anti-tumor M1 macrophages. Transcriptome sequencing indicated that FP-NPs significantly altered the expression of several genes involved in immunity. Analysis of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and quantitative real-time PCR revealed that FP-NPs significantly increased the expression of the myeloid cell differentiation-related gene interferon regulatory factor 7 and activated interferon beta-related signaling pathways, which stimulated the differentiation of MDSCs into M1 macrophages. These findings suggest that FP-NPs, a unique nanomaterial with immunological properties, can induce MDSCs to differentiate into M1 macrophages, potentially offering new treatment prospects for metastatic melanoma in the future.

Rational Design of Cu-Doped Tetrahedron of Spinel Oxide for High-Performance Nitric Oxide Electrochemical Sensor.

The real-time detection of nitric oxide (NO) in living cells is essential to reveal its physiological processes. However, the popular electrochemical detection strategy is limited to the utilization of noble metals. The development of new detection candidates without noble metal species still maintaining excellent catalytic performance has become a big challenge. Herein, we propose a spinel oxide doped with heteroatom-Cu-doped Co3O4 (Cu-Co3O4) for the sensitive and selective detection of NO release from the living cells. The material is strategically designed with Cu occupying the tetrahedral (Td) center of Co3O4 through the formation of a Cu-O bond. The introduced Cu regulates the local coordination environment and optimizes the electronic structure of Co3O4, hybridizing with the N 2p orbital to enhance charge transfer. The CuTd site can well inhibit the current response to nitrite (NO2-), resulting in a high improvement in the electrochemical oxidation of NO. The selectivity of Cu-Co3O4 can be markedly improved by the pore size of the molecular sieve and the negative charge on the surface. The rapid transmission of electrons is due to the fact that Cu-Co3O4 can be uniformly and densely in situ grown on Ti foil. The rationally designed Cu-Co3O4 sensor displays excellent catalytic activity toward NO oxidation with a low limit of detection of 2.0 nM (S/N = 3) and high sensitivity of 1.9 µA nM-1 cm-2 in cell culture medium. The Cu-Co3O4 sensor also shows good biocompatibility to monitor the real-time NO release from living cells (human umbilical vein endothelial cells: HUVECs; macrophage: RAW 264.7 cells). It was found that a remarkable response to NO was obtained in different living cells when stimulated by l-arginine (l-Arg). Moreover, the developed biosensor could be used for real-time monitoring of NO released from macrophages polarized to a M1/M2 phenotype. This cheap and convenient doping strategy shows universality and can be used for sensor design of other Cu-doped transition metal materials. The Cu-Co3O4 sensor presents an excellent example through the design of proper materials to implement unique sensing requirements and sheds light on the promising strategy for electrochemical sensor fabrication.

A Compact High-Isolation Four-Element MIMO Antenna with Asymptote-Shaped Structure.

The demand for high-speed wireless communication systems has led to the development of ultrawide-band (UWB) antennas with a compact size and high performance. In this paper, we propose a novel four-port multiple-input multiple-output (MIMO) antenna with an asymptote-shaped structure that overcomes the limitations of existing designs for UWB applications. The antenna elements are placed orthogonally to each other for polarization diversity, and each element features a stepped rectangular patch with a tapered microstrip feedline. The unique structure of the antenna significantly reduces its dimensions to 42 × 42 mm2 (0.43λ×0.43λ@ 3.09GHz), making it highly desirable for use in small wireless devices. To further enhance the antenna's performance, we use two parasitic tapes on the ground plane at the back as decoupling structures between adjacent elements. The tapes are designed in a windmill shape and a rotating extended cross shape, respectively, to further improve the isolation. We fabricated and measured the proposed antenna design on a single-layer substrate (FR4) with a dielectric constant of 4.4 and a thickness of 1 mm. The measured results show that the impedance bandwidth of the antenna is 3.09-12 GHz, with an isolation of -16.4 dB, an envelope correlation coefficient (ECC) of 0.02, a diversity gain (DG) of 9.991 dB, an average total effective reflection coefficient (TARC) of -20 dB, an overall group delay value less than 1.4 ns, and a peak gain of 5.1 dBi. Although there may be some antennas that have better performance in one or two specific aspects, our proposed antenna has an excellent trade-off among all the antenna characteristics including bandwidth, size, and isolation. The proposed antenna also exhibits good quasi-omnidirectional radiation properties, making it well-suited for a range of emerging UWB-MIMO communication systems, particularly in small wireless devices. In summary, the compact size and ultrawide-band capabilities of the proposed MIMO antenna design, coupled with its improved performance compared to other recent UWB-MIMO designs, make it a promising candidate for 5G and next-generation wireless communication systems.

The combinational nano-immunotherapy of ferumoxytol and poly(I:C) inhibits melanoma via boosting anti-angiogenic immunity.

Angiogenesis plays a key role in the progression and metastasis of melanoma, and the pro-angiogenic effect of macrophages is one major reason for the failure of current anti-angiogenic therapies. Here, a nano-immunotherapy combining ferumoxytol and poly(I:C) (ferumoxytol/poly(I:C)) has been developed to boost the anti-angiogenic activities of macrophages to inhibit melanoma. Our findings demonstrated that ferumoxytol/poly(I:C) was a highly efficacious anti-tumor therapy with limited toxicity. Both in vivo and in vitro experiments indicated that this combination was successful in impeding angiogenesis. Ferumoxytol/poly(I:C) was demonstrated to reduce the viability of endothelial cells, thus hindering tube formation. Particularly, ferumoxytol/poly(I:C) was able to polarize macrophages to the M1 phenotype and decrease the expression of vascular endothelial growth factor, which in turn amplified the anti-angiogenic properties of ferumoxytol/poly(I:C). This combination of ferumoxytol/poly(I:C) nano-immunotherapy enriches the anti-angiogenic therapeutic nature of ferumoxytol and will shed new light on the treatment of melanoma.

Hydrogen-substituted graphdiyne encapsulated cuprous oxide photocathode for efficient and stable photoelectrochemical water reduction.

Photoelectrochemical (PEC) water splitting is an appealing approach for "green" hydrogen generation. The natural p-type semiconductor of Cu2O is one of the most promising photocathode candidates for direct hydrogen generation. However, the Cu2O-based photocathodes still suffer severe self-photo-corrosion and fast surface electron-hole recombination issues. Herein, we propose a facile in-situ encapsulation strategy to protect Cu2O with hydrogen-substituted graphdiyne (HsGDY) and promote water reduction performance. The HsGDY encapsulated Cu2O nanowires (HsGDY@Cu2O NWs) photocathode demonstrates a high photocurrent density of -12.88 mA cm-2 at 0 V versus the reversible hydrogen electrode under 1 sun illumination, approaching to the theoretical value of Cu2O. The HsGDY@Cu2O NWs photocathode as well as presents excellent stability and contributes an impressive hydrogen generation rate of 218.2 ± 11.3 µmol h-1cm-2, which value has been further magnified to 861.1 ± 24.8 µmol h-1cm-2 under illumination of concentrated solar light. The in-situ encapsulation strategy opens an avenue for rational design photocathodes for efficient and stable PEC water reduction.

Zwitterionic Polymers Coating Antibiofouling Photoelectrochemical Aptasensor for In Vivo Antibiotic Metabolism Monitoring and Tracking.

Long-term in vivo monitoring and tracking of target molecules in living organism is essential to reveal vital physiological activity. However, undesirable contamination of protein and biological cells may bring serious biofouling issues. Herein, zwitterionic sulfobetaine methacrylate (SBMA) polymers are grafted on the TiO2 nanotube (NT) surface with polydopamine (PDA) as linker to fabricate a TiO2 NTs/PDA/SBMA photoelectrode. The TiO2 NTs/PDA/SBMA/aptamer-based PEC aptasensor can be sensitive and have selective detection of target molecules with excellent antibiofouling activity. Beneficial from the above advantages, the implantable micro-PEC aptasensor has implemented in vivo tracking and monitoring of the metabolism of antibiotics in a living mouse. The robust antibiofouling property generates new inquiries and an approach for long-standing questions in a new way for reliable and long-term sensing of vital biomolecules in complex biological fluids and uncovers a promising advance of intrinsic physiological mechanisms.

A Compact Four-Port MIMO Antenna for UWB Applications.

A compact four-port multiple-input multiple-output (MIMO) antenna for ultrawideband (UWB) applications is presented in this paper. The proposed antenna has four unit cell antennas. Each unit cell is placed orthogonal to its adjacent elements. The radiation element of each unit cell is composed of a cut semicircular patch and a stepped microstrip feed line. The whole ground on the back side consists of four parts of defective ground and their extended branches, which are connected through a "卍" structure. The main decoupling technology used in the MIMO antenna is polarization diversity. In addition, protruded ground and parasitic elements are added to achieve a higher isolation. This compact antenna has a small area of 45 mm × 45 mm and is printed on a single layer substrate (FR4) with an εr = 4.4 and a thickness of 1.6 mm. This antenna has an impedance bandwidth (S11 < −10 dB) of 3.1−13.1 GHz (123%) and an isolation of less than −17 dB. The envelope correction coefficient (ECC) is less than 0.02 and the average gain is 4 dBi. The ultrawide bandwidth and compact size of the proposed antenna make it a promising candidate for UWB applications.

An Adaptive Time-Varying Impedance Controller for Manipulators.

Aiming at the situation that the structural parameters of the general manipulators are uncertain, a time-varying impedance controller based on model reference adaptive control (MRAC) is proposed in this article. The proposed controller does not need to use acceleration-based feedback or to measure external loads and can tolerate considerable structure parameter errors. The global uniform asymptotic stability of the time-varying closed-loop system is analyzed, and a selection approach for control parameters is presented. It is demonstrated that, by using the proposed control parameter selection approach, the closed-loop system under the adaptive controller is equivalent to an existing result. The feasibility of the presented controller for the general manipulators is demonstrated by some numerical simulations.

Photoelectrochemical Antibacterial Platform Based on Rationally Designed Black TiO2-x Nanowires for Efficient Inactivation against Bacteria.

A hyphenated strategy for photoelectrochemical (PEC) disinfection is proposed with rationally designed black TiO2-x as a photoresponsive material. The PEC method, a fusion of electrochemistry and photocatalysis, is an innovative and effective way to improve photocatalytic performance, which imparts certain properties to the photoelectrode and greatly promotes the charge transfer, thus effectively inhibiting the recombination of carriers and greatly promoting the catalytic efficiency. The oxygen vacancy (Vo) engineering on TiO2 is conducted to obtain black TiO2-x, which shows a much larger light absorption region in the full solar spectrum than the pristine white TiO2 and presents excellent PEC sterilization performance. The bactericidal efficiency with the PEC method is 10 times higher than that with the photocatalytic method, inactivating 99% of bacteria within a short time of 30 min. In addition, the black titanium oxide nanowires (B-TiO2-x NWs) are grown on flexible carbon cloth (CC) to form a sandwich structural self-cleaning face mask. The bacteria adhering to the surface of the mask will be sterilized quickly and efficiently under the illumination of visible light. The face mask with the characteristics of superior antibacterial effect and long service lifetime will be used for epidemic prevention and reduce the second pollution.