ent-Herqueidiketal and epi-Peniciherqueinone Isolated from a Mushroom Derived Fungus Penicillium herquei YNJ-35.

A new polyaromatic metabolite, ent-herqueidiketal (1), and a new phenalenone derivative, epi-peniciherqueinone (2), along with twelve known compounds 3-14, were isolated from the fungus Penicillium herquei YNJ-35, a symbiotic fungus of Pulveroboletus brunneopunctatus collected from Nangunhe Nature Reserve, Yunnan Province, China. The structures of 1-14 and the absolute configurations of 1 and 2 were determined by their spectroscopic data or by their single-crystal X-ray diffraction analysis or optical rotation values. Compound 1 showed strong antibacterial activity against Staphylococcus aureus (ATCC 29213) with minimum inhibitory concentration (MIC) of 8 µg/mL. In the cytotoxicity assays, compound 1 showed weak inhibitory activity against breast cancer MCF-7 and mice microglial BV2 cells with half maximal inhibitory concentration (IC50 ) of 17.58 and 29.56 µM; compound 14 showed stronger cytotoxicity against BV2 and MCF-7 cells with IC50 values of 6.57 and 10.26 µM.

Atomically Site Synergistic Effects of Dual-Atom Nanozyme Enhances Peroxidase-like Properties.

Pursuing effective and generalized strategies for modulating the electronic structures of atomically dispersed nanozymes with remarkable catalytic performance is exceptionally attractive yet challenging. Herein, we developed a facile "formamide condensation and carbonization" strategy to fabricate a library of single-atom (M1-NC; 6 types) and dual-atom (M1/M2-NC; 13 types) metal-nitrogen-carbon nanozymes (M = Fe, Co, Ni, Mn, Ru, Cu) to reveal peroxidase- (POD-) like activities. The Fe1Co1-NC dual-atom nanozyme with Fe1-N4/Co1-N4 coordination displayed the highest POD-like activity. Density functional theory (DFT) calculations revealed that the Co atom site synergistically affects the d-band center position of the Fe atom site and served as the second reaction center, which contributes to better POD-like activity. Finally, Fe1Co1 NC was shown to be effective in inhibiting tumor growth both in vitro and in vivo, suggesting that diatomic synergy is an effective strategy for developing artificial nanozymes as novel nanocatalytic therapeutics.

Bio-inspired nanozyme with ultra-thin Fe-Bi2O2S nanosheets for in-situ amplified photoelectrochemical immunoassay of cancer-related protein.

A Fe-loaded Bi2O2S nanosheet photoanode serving as photoelectric biomonitoring platform for the detection of prostate-specific antigen (PSA) using biologically inspired prussian nanoparticle (PB)-catalyzed biocatalytic precipitation strategy was developed. Primarily, the signal probe PB-mAb2 obtained by electrostatic adsorption was immobilized on a microplate in the presence of target PSA, and 4-chloro-1-naphthol (4-CN) was oxidized to benzo-4-chloro-hexadienone (4-CD) with the assistance of exogenous hydrogen peroxide, which was generated by a large number of hydroxyl radicals catalyzed by PB. The generated 4-CD showed strongly low conductivity characteristics to burst the photocurrent of highly photoactive Fe-Bi2O2S photoanode. The split incubation reaction could be suitable for high volume and low-cost rapid detection. A dynamic response range of 0.1-100 ng mL-1 with a limit of detection of 34.2 pg mL-1 was achieved with the sensor based on a photoelectric sensing platform and a biomimetic catalytic precipitation reaction. Equally important, the sensor also showed good potential in the detection of real samples compared to commercially available ELISA kits. In conclusion, this work provides a fresh scheme for the development of sensitive biosensors through a bio-inspired catalytic strategy of versatility and a photoanode coupling with high photoelectric activity.

Integrated solar-powered MEMS-based photoelectrochemical immunoassay for point-of-care testing of cTnI protein.

Considering the fact that acute myocardial infarction has shown a trend towards younger age and has become a major health problem, it is necessary to develop rapid screening devices to meet the needs of community health care. Herein, we developed an artificial neural network-assisted solar-powered photoelectrochemical (SP-PEC) sensing platform for rapid screening of cardiac troponin I (cTnI) protein in the prognosis of patients with acute myocardial infarction (AMI) by integrating a self-powered photoelectric signal output system with low-cost screen-printed paper electrodes functionalized with ultrathin Bi2O2S (BOS) nanosheets. An integrated solar-powered PEC immunoassay with micro-electro-mechanical system (MEMS) was constructed without an excitation light source. The quantification of cTnI protein was obtained by the electrical signal changes caused by the electro-oxidation process of H2O2, generated by the classical split immune reaction, on the electrode surface. The test electrodes were developed as dual working electrodes, one for target cTnI testing and the other for evaluating light intensity, to reduce the temporal inconsistency of sunlight. The photoelectrodes were discovered to exhibit satisfactory negative response to target concentrations in the dynamic range of 2.0 pg mL-1-10 ng mL-1 since being regressed in an improved artificial neural network (ANN) model using the pooled dataset of target signals affected by the light source. The difference of hot electron and hole transfer behavior in different thickness of nano-materials was determined by finite element analysis (FEA), which provided a theoretical basis for the development of efficient PEC sensors. This work presents a unique perspective for the design of a revolutionary low-cost bioassay platform by inventively illuminating the PEC biosensor's component process without the use of light.

Hollow prussian blue nanozyme-richened liposome for artificial neural network-assisted multimodal colorimetric-photothermal immunoassay on smartphone.

Multi-signal output biosensor technologies based on optical visualization and electrochemical or other sophisticated signal transduction are flourishing. However, sensors with multiple signal outputs still exhibit some limitations, such as the additional requirement for multiple regression equation construction and control of results. Herein, we developed a sensitive cascade of colorimetric-photothermal biosensor models for prognostic management of patients with myocardial infarction with the assistance of an artificial neural network (ANN) normalization process. A cascade enzymatic reaction device based on hollow prussian blue nanoparticles (h-PB NPs), and a portable smartphone-adapted signal visualization platform were integrated into the all-in-one 3D printed assay device. Specifically, liposomes encapsulated with h-PB were confined to the test cell using a classical immunoassay. Based on the peroxidase-like activity of h-PB, the h-PB obtained by the immunization process was further transferred to the TMB-H2O2 system and used as a cascade of signal amplification for sensitive determination of cTnI protein. The target concentration was converted into a measurable temperature signal readout under 808 nm NIR laser excitation, and the absorbance of the TMB (ox-TMB) system at 650 nm was recorded simultaneously as a reference during this process. Interestingly, a parallel 3-layer, 64-neuron ANN learning model was built for bimodal signal processing and regression. Under optimal conditions, the bimodal machine learning-assisted co-immunoassay exhibited an ultra-wide dynamic range of 0.02-20 ng mL-1 and a detection limit of 10.8 pg mL-1. This work creatively presents a theoretical study of machine learning-assisted multimodal biosensors, providing new insights for the development of ultrasensitive non-enzymatic biosensors.

Flexible and High-Throughput Photothermal Biosensors for Rapid Screening of Acute Myocardial Infarction Using Thermochromic Paper-Based Image Analysis.

Herein, we developed a flexible, low-cost thermosensitive fiber paper for the visual display in photothermal biosensing systems for early acute myocardial infarction. The thermal signal visualization device was encapsulated with rewritable thermal fibers, which exhibited excellent stability and reversibility. The mechanism of color change in thermal paper was based on a temperature-driven reversible transformation of the structure of the dye molecule (crystalline violet lactone, CVL). It exhibits a gradation from blue to colorless at higher temperatures and gradually returns to blue when the temperature drops. Immobilization and cascade enzymatic reactions of target molecules occurred in an integrated 3D-printed detection device, a photothermal conversion process occurred under near-infrared light excitation, and the colorimetric change values of the encapsulated thermal paper were recorded and evaluated for possible pathogenicity using a smartphone. It was worth noting that the effect of the thermogenic ring-opening behavior of CVL on the macroscopic phenomenon of color change was obtained by density functional theory calculations. Under optimized conditions, the naked-eye-recognizable range of the thermal paper-based photothermal immunoassay sensor was 0.2-20 ng mL-1, This work creatively presents theoretical studies of promising thermal paper-based photothermal biosensors and provides new insights for the development of low-cost, instrument-free portable photothermal biosensors.

Integrated Photothermal-Pyroelectric Biosensor for Rapid and Point-of-Care Diagnosis of Acute Myocardial Infarction: A Convergence of Theoretical Research and Commercialization.

Acute myocardial infarction (AMI) survivors face a high risk of mortality as a result of increasing heart failure and irreparable myocardial injury. New portable methods for immediate diagnosis must be developed to provide patients with daily warnings. Herein, the development of a dual-mode photothermal-pyroelectric output system based on a point-of-care platform for rapid AMI detection is reported. Termed as Integrated Photothermal-Pyroelectric Biosensor for AMI (IPPBA), the method leverages cascade enzymatic amplification to convert the target signal into a thermal and pyrooelectric conversion of the testing process by delicate pyroelectric pervokite NaNbO3 nanocubes modified microelectrodes for sensitive detection of cTnI protein in whole blood. In addition, the mechanism of the proposed pyroelectric bioassay model is explored in depth based on in situ variable temperature X-ray diffraction (XRD) lattice change statistics and density function theory (DFT) calculations. With standard samples and under optimized experimental conditions, the proposed IPPBA platform exhibits excellent signal stability and ultra-low detection limit (0.05 ng mL-1 ) for the target cTn I. With further developments in digital technology (e.g., 5G signaling protocols, fully automated systems), the integrated digital bio-testing platform IPPBA is fully capable of accomplishing positive and timely diagnosis of AMI.

Liposome-Embedded Cu2-xAgxS Nanoparticle-Mediated Photothermal Immunoassay for Daily Monitoring of cTnI Protein Using a Portable Thermal Imager.

Functional photothermal nanomaterials have gained widespread attention in the field of precise cancer therapy and early disease diagnosis due to their unique photothermal conversion properties. However, the relatively narrow temperature response range and the outputable accuracy of commercial thermometers limit the accurate detection of biomarkers. Herein, we designed a liposome-embedded Cu2-xAgxS amplification-based photothermal sensor for the accurate determination of cardiac troponin I (cTnI) in health monitoring and point-of-care testing (POCT). The combinable 3D-printing detecting device monitored and visualized target signal changes in the testing system under the excitation of near-infrared (NIR) light, which was recorded and evaluated for possible pathogenicity by a smartphone. Notably, we predicted the potentially efficient thermal conversion efficiency of Cu2-xAgxS from the structure and charge density distribution, calculated by the first-principles and density functional theory (DFT), which provided a theoretical basis for the construction of novel photothermal materials, and the experimental results proved the correctness of the theoretical projections. Under optimal conditions, the photothermal immunoassay showed a dynamic linear range of 0.02-10 ng mL-1 with a detection limit of 11.2 pg mL-1. This work instructively introduces promising theoretical research and provides new insights for the development of sensitive portable photothermal biosensors.

Size-Controlled Engineering Photoelectrochemical Biosensor for Human Papillomavirus-16 Based on CRISPR-Cas12a-Induced Disassembly of Z-Scheme Heterojunctions.

Photoelectrochemical (PEC) biosensors incorporating biomolecular recognition with photon-to-electron conversion capabilities of the photoactive species have been developed for molecular diagnosis, but most involve difficulty in adjusting band gap positions and are unsuitable for PEC biodetection. In this work, an innovative PEC biosensor combined with quantum size-controlled engineering based on quantum confinement by controlling the quantum size was designed for the detection of human papillomavirus-16 (HPV-16) through CRISPR-Cas12a (Cpf1)-induced disassembly of Z-scheme heterojunction. To the best of our knowledge, quantum size-controlled engineering that precisely tunes the properties of photoactive materials is first utilized in the PEC bioanalysis. Based on the quantum size effect, the light absorption efficiency and charge-transfer rate were tuned to suitable levels to obtain the best PEC performance. After incubation with target HPV-16, the binding of Cas12a-crRNA to the target double-stranded DNA (dsDNA) stimulated the activity of indiscriminate cleavage toward single-stranded DNA (ssDNA), resulting in a decrease in photocurrent due to the blocking of electron transfer through the heterojunction. By optimizing experimental conditions, the Z-scheme sensing system exhibited incredible photocurrent response to HPV-16 in the range from 3.0 pM to 600 nM with a detection limit of 1.0 pM. Impressively, the application of the quantum size effect could stimulate more interest in the precise design of band gap structure to improve PEC performance.

CRISPR-Cas12a-Derived Photoelectrochemical Biosensor for Point-Of-Care Diagnosis of Nucleic Acid.

This work presented a point-of-care (POC) photoelectrochemical (PEC) biosensing for the detection of human papillomavirus-16 (HPV-16) on a portable electrochemical detection system by using CRISPR-Cas12a trans-cleaving the G-quadruplex for the biorecognition/amplification and a hollow In2O3-In2S3-modified screen-printed electrode (In2O3-In2S3/SPE) as the photoactive material. G-quadruplexes were capable of biocatalytic precipitation (H2O2-mediated 4-chloro-1-naphthol oxidation) on the In2O3-In2S3/SPE surface, resulting in a weakened photocurrent, but suffered from trans-cleavage when the CRISPR-Cas12a system specifically recognized the analyte. The photocurrent results could be directly observed with the card-sized electrochemical device via a smartphone, which displayed a high-value photocurrent for these positive samples, while a low-value photocurrent for the target-free samples. Such a system exhibited satisfying photocurrent responses toward HPV-16 within a wide working range from 5.0 to 5000 pM and allowed for detection of HPV-16 at a concentration as low as 1.2 pM. The proposed assay provided a smartphone signal readout to enable the rapid screening PEC determination of HPV-16 concentration without sophisticated instruments, thus meeting the requirements of remote areas and resource-limited settings. We envision that combining an efficient biometric PEC sensing platform with a wireless card-sized electrochemical device will enable high-throughput POC diagnostic analysis.

Exploiting Photoelectric Activities and Piezoelectric Properties of NaNbO3 Semiconductors for Point-of-Care Immunoassay.

Point-of-care testing (POCT) technology has made major breakthroughs in community medicine and physician office situations, in tandem with the more ubiquitous and intensive usage of highly integrated quick detection equipment for illness diagnosis, personal care, and mobile healthcare. Although the photoelectrochemical (PEC)-based POCT platform offers the benefits of cheap cost and good user engagement, its commercialization is still limited by the photodetection components' downsizing and mobility, among other factors. In this work, a novel highly integrated PEC biosensor aided by piezophototronics to enhance the efficiency of PEC testing was reported for flexible detection of cancer-associated antigens in biological fluids (prostate-specific antigen, PSA, used as an example). Multiple signal enhancement strategies, including a magnetic bead-linked enzyme-linked immune system catalyzing the production of ascorbic acid from the substrate and a piezoelectric-assisted enhancement strategy, were used for sensitive detection of the analyte to be tested in human body fluids. Unlike the electron transfer mechanism in heterojunctions, piezoelectric semiconductors promote the transfer of electrons and holes by generating piezoelectric potentials in the ultrasonic field, thus contributing to the performance of the PEC testbed. Under optimized conditions, the test platform achieves good correspondence for PSA at 0.02-40 ng mL-1. Impressively, the test devices are comparable to or even superior to gold standard ELISA kits in terms of cost approval and batch testing. This research demonstrates the potential of piezoelectric semiconductors for POC applications in revolutionary PECs and offers innovative thoughts for the development of new PEC bioanalytical components.

Bioinspired Self-Powered Piezoresistive Sensors for Simultaneous Monitoring of Human Health and Outdoor UV Light Intensity.

The exact fabrication of precise three-dimensional structures for piezoresistive sensors necessitates superior manufacturing methods or tooling, which are accompanied by time-consuming processes and the potential for environmental harm. Herein, we demonstrated a method for in situ synthesis of zinc oxide nanorod (ZnO NR) arrays on graphene-treated cotton and paper substrates and constructed highly sensitive, flexible, wearable, and chemically stable strain sensors. Based on the structure of pine trees and needles in nature, the hybrid sensing layer consisted of graphene-attached cotton or paper fibers and ZnO NRs, and the results showed a high sensitivity of 0.389, 0.095, and 0.029 kPa-1 and an ultra-wide linear range of 0-100 kPa of this sensor under optimal conditions. Our study found that water absorption and swelling of graphene fibers and the associated reduction of pore size and growth of zinc oxide were detrimental to pressure sensor performance. A random line model was developed to examine the effects of different hydrothermal times on sensor performance. Meanwhile, pulse detection, respiration detection, speech recognition, and motion detection, including finger movements, walking, and throat movements, were used to show their practical application in human health activity monitoring. In addition, monolithically grown ZnO NRs on graphene cotton sheets had been integrated into a flexible sensing platform for outdoor UV photo-indication, which is, to our knowledge, the first successful case of an integrated UV photo-detector and motion sensor. Due to its excellent strain detection and UV detection abilities, these strategies are a step forward in developing wearable sensors that are cost-controllable and high-performance.

Graphene-coated copper-doped ZnO quantum dots for sensitive photoelectrochemical bioanalysis of thrombin triggered by DNA nanoflowers.

This work reports a photoelectrochemical (PEC) biosensing platform for the sensitive and specific screening of thrombin by using graphene oxide-coated copper-doped zinc oxide quantum dots (Cu0.3Zn0.7O-GO QDs) as the photoactive materials and glucose oxidase-encapsulated DNA nanoflowers (GOx-DFs) for signal amplification. Interestingly, the coated graphene oxide nanosheets on the surface of the Cu0.3Zn0.7O QDs could cause the charge to transfer rapidly and ameliorate the photocorrosion. The doped copper into the quantum dots could enhance the absorption of visible light by tuning the band gap of ZnO QDs, therefore increasing the photocurrent under visible irradiation. Upon addition of target thrombin, a sandwiched reaction was carried out between thrombin aptamer and GOx-DFs, accompanying the formation of nanocomposites with the magnetic microparticles (MMPs)/thrombin/GOx-DFs. Followed by magnetic separation, the carried GOx oxidized glucose to H2O2, thus resulting in the increasing photocurrent of the Cu0.3Zn0.7O-GO QD-modified electrode. Under optimum conditions, the developed PEC biosensing platform exhibited good analytical performance with a linear range of 50-10 000 fM thrombin and a limit of detection of 29 fM. Impressively, our strategy offers a new horizon in developing bridge-connected graphene-coated nanomaterials and novel signal amplification strategy for the development of PEC biosensors.

Chemiluminescence-Derived Self-Powered Photoelectrochemical Immunoassay for Detecting a Low-Abundance Disease-Related Protein.

Early diagnosis of cancers relies on the sensitive detection of specific biomarkers, but most of the current testing methods are inaccessible to home healthcare due to cumbersome steps, prolonged testing time, and utilization of toxic and hazardous substances. Herein, we developed a portable self-powered photoelectrochemical (PEC) sensing platform for rapid detection of prostate-specific antigen (PSA, as a model disease-related protein) by integrating a self-powered photoelectric signal output system catalyzed with chemiluminescence-functionalized Au nanoparticles (AuNPs) and a phosphomolybdic acid (PMA)-based photochromic visualization platform. TiO2-g-C3N4-PMA photosensitive materials were first synthesized and functionalized on a sensor chip. The sensor consisted of filter paper modified with a photocatalytic material and a regional laser-etched FTO electrode as an alternative to a conventional PEC sensor with a glass-based electrode. The targeting system involved a monoclonal anti-PSA capture antibody-functionalized Fe3O4 magnetic bead (mAb1-MB) and a polyclonal anti-PSA antibody (pAb2)-N-(4-aminobutyl)-N-ethylisoluminol-AuNP (ABEI-AuNP). Based on the signal intensity of the chemiluminescent system, the photochromic device color changed from light yellow to heteropoly blue through the PMA photoelectric materials integrated into the electrode for visualization of the signal output. In addition, the electrical signal in the PEC system was amplified by a sandwich-type capacitor and readout on a handheld digital multimeter. Under optimum conditions, the sensor exhibited high sensitivity relative to PSA in the range of 0.01-50 ng mL-1 with a low detection limit of 6.25 pg mL-1. The flow-through chemiluminescence reactor with a semiautomatic injection device and magnetic separation was avoid of unstable light source intensity inherent in the chemiluminescence process. Therefore, our strategy provides a new horizon for point-of-care analysis and rapid cost-effective clinical diagnosis.

CRISPR/Cas12a-mediated liposome-amplified strategy for the photoelectrochemical detection of nucleic acid.

This study reports a photoelectrochemical biosensor for dopamine-loaded liposome-encoded magnetic beads cleaved by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas 12a system for the quantification of human papilloma virus (HPV)-related DNA using neodymium-doped BiOBr nanosheets (Nd-BiOBr) as a photoactive matrix. Magnetic beads and dopamine-loaded liposomes are covalently attached to the both ends of ssDNA to construct dumbbell-shaped dopamine-loaded liposome-encoded magnetic bead (DLL-MB) probes. When the guide RNA binds to the target HPV-16, the ssDNA will be cleaved by Cas12a, thereby degrading the double dumbbell probes. After magnetic separation, the dissolved DLLs are treated with Triton X-100 to release the dopamine (as an electron donor), which was then detected by an amplified photocurrent using the Nd-BiOBr-based photoelectrode.