Near-infrared light (NIR)-driven photoelectrochemical (PEC) processes are mainly faced with the limitation of weak photocurrents. Here, N-deficient B-doped g-C3N4/CdS (NB-g-C3N4/CdS) is proposed to construct a NIR-driven PEC biosensor assisted by CRISPR-Cas12a system for the determination of microRNA-21 (miRNA-21). To promote the optical absorption as well as the separation of photogenerated electrons and holes of g-C3N4, NB-g-C3N4/CdS is constructed via engineering the electronic and band structure in terms of N defect, B doping, and heterojunction, achieving high PEC performance. To obtain the high luminescence efficiency for exciting NB-g-C3N4/CdS under NIR, the core-shell NaYF4:Yb3+, Tm3+@NaYF4 upconversion nanoparticles (UCNPs) with repaired defects are prepared. Furthermore, the rolling circle amplification (RCA)-assisted CRISPR-Cas12a system is integrated to fragment the DNA on UCNPs, achieving sensitive detection of miRNA-21. On the one hand, the uncleavaged signal probes on UCNPs combined with NB-g-C3N4/CdS through π-π stacking interaction, generating photocurrents under the irradiation of NIR. On the other hand, the cleavaged signal probes which cannot link with NB-g-C3N4/CdS exhibited the fluorescence (FL) signals. The proposed PEC-FL dual-mode biosensor provides a mutual authentication of testing results and demonstrates ultrasensitivity (the detection limit of 1.1 fM for PEC mode and 7.0 fM for FL mode) and excellent specificity, which is promising in the clinical analysis of miRNA.

Abnormal alkaline phosphatase (ALP) levels in the human body are closely associated with various diseases, particularly hepatobiliary diseases and bone diseases. Herein, we constructed a ratiometric sensor based on Förster resonance energy transfer (FRET) using strongly photoluminescent copper nanoclusters (Cu NCs) for the detection of ALP with high sensitivity and specificity. The cysteine-stabilized Cu NCs (Cys-Cu NCs) were synthesized through a ligand-exchange reaction and core-size etching focusing, which displayed bright photoluminescence (PL) with a quantum yield (QY) of 10.5 %. Multispectral characterization indicated that zwitterionic cysteine ligands without obvious steric hindrance could significantly enhance intra/inter-ligand-involved charge transfer, leading to a significant increase in fluorescence emission (∼14 folds) compared to precursor Cu NCs. A FRET-based ratiometric sensor for ALP detection was constructed by combining Cys-Cu NCs with a Cu2+-assisted oxidation reaction of o-phenylenediamine (OPD) to generate fluorescent 2,3-diaminophenazine (DAP). The strong coordination interaction between the ALP substrate and Cu2+ significantly affected the FRET process between Cys-Cu NCs and DAP, thereby altering the fluorescence ratio. Based on the specific response of ALP to its substrate, the ratiometric sensors showed good linear relationship within the range of 0.1-50 U/L, with a detection limit (LOD) of 0.075 U/L. Furthermore, the FRET-based ratiometric sensor was integrated with a polymer hydrogel to fabricate a portable hydrogel sensor for simple and visual detection of ALP.

A molecular beacon is an oligonucleotide hybridization probe that can report the presence of specific nucleic acids in homogeneous solutions. Using an aptamer has allowed an aptamer-based molecular beacon–aptamer beacon to be developed, which has shown advantages of simplicity, rapidity, and sensitivity in imaging and sensing non-nucleic acid substances. However, due to requirement for a deliberate DNA hairpin structure for the preparation of a molecular beacon, not any given aptamer is suitable for designing an aptamer beacon probe. This paper provides a general design strategy for the preparation of an aptamer beacon probe, which theoretically can be used for any given aptamer. Through coupling an aptamer and a short complementary DNA into one DNA molecule via a rational poly thymidine (T) linker, novel molecular beacon probes are successfully prepared and used for the detection of targets (aflatoxin B1 and ochratoxin A). The working mechanism of this aptamer beacon probe is based on intramolecular hybridization/dehybridization, which is more efficient than commonly aptasensor strategies based on intermolecular reactions. This aptamer beacon probe shows advantages of low background, a signal-on response, a large signal change, as well as simplicity and rapidity of analysis, which have promising application potential.

Achieving high product selectivity at ampere-level current densities is essential for the industrial application of electrochemical CO 2 reduction. However, the operational stability of CO 2 electrolyzers at large current density has long been hindered by flooding of gas diffusion layer (GDL). Herein, a new heteroarchitectural GDL is designed to overcome flooding. Such GDL is constructed by sequentially sputtering the conductive silver and titanium boride (TiB 2 ) onto a polytetrafluoroethylene substrate. Assembled with Cu catalyst in a flow cell, a maximum ethylene Faradaic efficiency of 64.7 % was achieved at a current density of 1.2 A cm −2 in 6 M KOH. Furthermore, the GDL is capable of stable operation for over 40 hours at 400 mA cm −2 . Theoretical calculations and in situ experiments demonstrate enhanced intermediates adsorption on the TiB 2 -supported Cu surface, thereby reducing the energy barrier for C−C coupling. When coupling the CO 2 reduction reaction with 5-hydroxymethylfurfural oxidation reaction, Faradaic efficiencies of 49.2 % for ethylene and 85.4 % for 2,5-furandicarboxylic acid were achieved at 1.2 A cm −2 . This work provides a highly stable GDL for efficient CO 2 conversion at ampere-level current density and paves the way for integrating biomolecules conversion in stack-level devices.

Drug-induced liver injury (DILI) has emerged as an urgent clinical challenge. It is characterized by mitochondrial dysfunction in liver cells, which leads to abnormal changes in H2O2 levels within the mitochondria. Super-resolution imaging allows for the observation of the fine structure of mitochondria at the nanometer scale, potentially enabling the detection of mitochondrial H2O2 levels during DILI at the subcellular organelle level. Here, we report the design and synthesis of a novel H2O2-activated probe for the detection of mitochondrial H2O2 levels. SML is a near-infrared (NIR) fluorescent probe with a large Stokes shift (260 nm) and a sensing mechanism based on intramolecular charge transfer (ICT) switching. Super-resolution imaging of mitochondrial H2O2 was conducted using structured illumination microscopy (SIM). The improved accuracy in observing periods of mitochondrial dysfunction allows the SML probe to be effectively utilized for the rapid monitoring nanoscale upregulation of H2O2 during DILI and hepatic fibrosis, thus providing SML with the capability to screen for effective therapeutic candidates.

Tracing copper ions levels in the environment and subcellular microenvironment is crucial due to the key role copper ions play in physiological and pathological processes. Herein, a novel naphthalimide-fused rhodamine probe Rh-Naph-Cu was prepared through modification with phenylhydrazine to produce a closed and non- fluorescent spirolactam. Based on the copper-induced spirolactam ring-opening and hydrolysis process, RhNaph-Cu can be employed as a fluorescence off-on probe for copper ions with high selectivity, high sensitivity (limit of detection: 33.0 nM), broad pH-response range (pH: 5.0-10.0), and color change visible with the naked eye. Rh-Nap-Cu could be made into test strips for the in-situ chromogenic detection of Cu2+. Significantly, RhNaph-Cu can be utilized for the detection of copper ions in living HeLa cells and zebrafish, and exhibits excellent lysosomal-targeting ability with high Pearson's correlation coefficient (PCC) of 0.96.

Water splitting as the clean technology for hydrogen production garnered the widespread attention. The high overpotential required for oxygen evolution reaction (OER) is the central dilemma. Herein, Co-Ni3B/graphdiyne heterostructure on copper foam (Co-Ni3B/GDY/CF) was constructed for boosting alkaline OER. Detailed electrochemical analysis showed that Co-Ni3B/GDY/CF was an exceptional OER electrocatalyst with the low overpotentials of 270 and 335mV at 20 and 100mAcm−2 in 1.0M KOH solution, respectively, as well as high turnover frequency of 0.80s−1 at 400mV. Moreover, its catalytic performance outperformed the benchmarked RuO2/CF when the current density exceeded 200mAcm−2. Importantly, the equipped electrolyser Pt/C/CF||Co-Ni3B/GDY/CF showed low cell voltage (1.53V@10mAcm−2) and long-term durability. These results demonstrated that a synergistic effect at the heterointerface between GDY and Co-Ni3B was achieved, which regulated the electronic configuration, accelerated the charge transfer and increased the active surface areas. Furthermore, the density functional theory calculations revealed that Co-Ni3B/GDY with incomplete charge transfer lowered the energy barrier of the rate-determining step and optimized adsorption/desorption behavior of the intermediates, thereby effectively promoting O2 evolution.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@Co3O4-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified Co3O4 nanoparticles decorated metal-organic framework PCN-224. Co3O4 can catalyze the decomposition of highly expressed H2O2 in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@Co3O4-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@Co3O4-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@Co3O4-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.

The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) in tumor treatment has attracted considerable attention. However, tumor hypoxia and glutathione (GSH) overproduction in the tumor tissue restricted the progress of their applications. Herein, a Mn-porphyrinic metal–organic framework (Mn-TCPP) was constructed by the one-pot method and further used for immobilizing glucose oxidase (GOx) to obtain GOx@Mn-TCPP. GOx would rapidly exhaust endogenous glucose into hydrogen peroxide (H2O2) and gluconic acid, thus shutting off the energy supply of tumor cells for starvation treatment. Mn-TCPP catalyzed H2O2 to produce oxygen, regulating the hypoxic tumor microenvironment and in turn improving 1O2 generation under laser irradiation. Interestingly, Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+ and GSH, thus greatly enhancing PDT. Furthermore, benefiting from GOx-mediated starvation therapy, Mn2+ produced by Mn3+ reduction can react with sufficient intracellular H2O2 to generate ·OH with high cytotoxicity through a Fenton-like reaction. After treatment by GOx@Mn-TCPP under laser irradiation in vitro, the cell viability of 4T1 and A549 tumor cells reached to 20

MicroRNA(miRNA) serves as an effective and viable biomarker for early diagnosis and monitoring of cancer disorders. It is highly expressed in tumor cells, including lung cancer, liver cancer and lymphoma. Herein, we propose a ratiometric electrochemical sensor for ultrasensitive detection of miRNA-21 using dual signal amplification, hybridization chain reaction and Exo III assisted-amplification. Methylene blue (MB) and Hemin are chosen as two electrochemical species. Then the ratiometric electrochemical sensor were developed, which showed favorable performance of miRNA-21 detection, and exhibited a detection concentration range from 1 fM to 10 nM. Notably, the limit of detection for this biosensor was 0.15 fM. Overall, this strategy for miRNA detection holds significant promise for early cancer screening.

Objective: To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province. Methods: This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized. Results: Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion: Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Nanozymes, as an emerging class of enzyme mimics, have attracted much attention due to their adjustable catalytic activity, low cost, easy modification, and good stability. Researchers have made great efforts in developing and applying high-performance nanozymes. Recently, transition-metal-based nanozymes have been designed and widely developed because they possess unique photoelectric properties and high enzyme-like catalytic activities. To highlight these achievements and help researchers to understand the research status of transition-metal-based nanozymes, the development of transition-metal-based nanozymes from material characteristics to biological applications is summarized. Herein, we focus on introducing six categories of transition-metal-based nanozymes and highlight their progress in biomarker sensing and catalytic therapy for tumors. We hope that this review can guide the further development of transition-metal-based nanozymes and promote their practical applications in cancer diagnosis and treatment.

Luminescent Ag nanoclusters (Ag NCs) are a promising probe material for sensing and bioimaging applications. However, the intrinsic obstacle of poor water stability and photostability greatly restrict their practical application in biological systems. Herein, we report the intracellular hypochlorite (ClO−) detection with amphiphilic copolymer-modified luminescent Ag NCs with good biocompatibility and photostability. The Ag NCs were synthesized by using chemically inert hydrophobic ligands and then modified with an amphiphilic (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000]) (DSPE-PEG-2000) and sodium dodecyl sulfonate (SDS) for phase transfer. It was found that the approach of the removal of organic solvents during the phase transfer has remarkable influences on the properties of the Ag NCs, including their size, luminescence property, and aqueous stability. Furthermore, the silver core of Ag NCs could be oxidatively damaged by ClO−, thereby causing photoluminescence (PL) quenching. The ClO−-induced PL quenching was specific over the other common reactive oxygen species (ROS) as well as some common interferences. Finally, they have been successfully applied as a fluorescent nanoprobe for detecting exogenous and endogenous ClO− in living cells.

The controllable geometry and multifunctionality of DNA nano-bioreactors hold immense promise for disease diagnosis. Herein, a facile rolling circle amplification (RCA)-based crystallization method has been developed for highly efficient self-assembly of three-dimensional (3D) DNA nano-bioreactors, which show excellent cascade catalytic performance by confining bio-enzyme (glucose oxidase (GOx) used in this case) and copper ions (Cu2+) in DNA nanoflowers (DNFs) structure. The participation of Cu2+ during the self-assembly process not only endows the nano-bioreactors (designated as GOx/Cu@DNFs) with inspiring peroxidase-like activity but also greatly improves the assembly efficiency and yield via the effective coordination between Cu2+ and RCA-generated long concatemeric DNAs. The integration of GOx and Cu2+ in the constrained flower-like DNA nanomatrices makes for the efficient inter-catalyst communication, resulting in the striking enhancement of biocatalytic cascade activity. Based on the prepared nano-bioreactors, a colorimetric biosensor has been constructed for glucose detection, achieving a wide linear range (2-400 μM) and a low detection limit (0.45 μM). Furthermore, the proposed sensing strategy enables the accurate determination and discrimination of glucose levels in healthy and diabetic sera, delivering gratifying outcomes. Overall, the meticulously crafted cascade nano-bioreactors not only illuminate the design of multifunctional nanomaterials based on RCA, but also expand the conceptual framework of the universal analytical method for determining small molecules with catalytic reactions to generate H2O2.

Progressive collapse resistance is more critical for precast concrete than cast-in-place structures. Most existing studies utilized scaled-down and quasi-static pushdown tests on substructures with rigid constraints under key member failure scenarios. However, the connection details, the spatial action of floors and the constraint stiffness of the remaining structure significantly affect the structure's progressive collapse resistance. Full-scale structural testing is the most direct method to evaluate the progressive collapse resistance of a new prefabricated structure, although it is difficult and costly to load and measure. A 2 x 2 bay 5-story full-scale frame structure was constructed according to the minimum requirements of the Code for Seismic Design of Buildings to investigate the progressive collapse resistance of a new precast, prestressed, efficiently fabricated frame (PPEFF) system. The structure's dynamic performance was analyzed by removing the 4th-floor edge column and bottom corner column. The slider and double micro-friction surface configuration proved suitable for the rapid removal of large axial force columns in a full-scale progressive collapse experiment. The layout of the full-scale structural test and the structure's dynamic responses are described. The effect of the lateral constraint stiffness and the duration of column removal on the dynamic response of the test structure were analyzed using finite element analysis. The progressive collapse resistance mechanism of the PPEFF structure was discussed. The PPEFF system remained in an elastic state and exhibited good progressive collapse resistance.

Peroxynitrite (ONOO-) is a critical biomarker associated with a wide array of diseases including cancer, inflammatory conditions, and neurodegenerative disorders. This study introduces an innovative chemiluminescence nanoprobe (CLNP) based on a bicyclic dioxetane structure, designed for highly sensitive and specific in vivo imaging of ONOO-. Our CLNP demonstrates exceptional capabilities in generating high-contrast imaging of disease lesions, with applications verified across tumor models, acute inflammation, and acute liver injury scenarios. Key findings highlight the probe's rapid response to oxidative species, superior tissue penetration, and high signal-to-noise ratio, underscoring its potential for real-time diagnostic applications. This work represents an important advance in the field of diagnostic imaging using CL probes, offering promising avenues for the early detection and treatment of ONOO--related pathologies.

A new kind of Precast Prestressed Efficiently Fabricated Frame (PPEFF) system known as the PPEFF system has been used in China for several years, however there are few reports in English. Based on the hybrid frame system, the PPEFF system adds a post-cast composite layer on the top of the precast beam-slab and eliminates the energy dissipation rebars at the lower part of the beam-column joint. This makes it easier to compose a two-way moment-resisting frame without reinforcement congestion in the joint and simplifies the construction of the slab-beam-column joint. This paper introduces the PPEFF system and establishes a nonlinear finite element model that can accurately simulate the seismic performance of the PPEFF joint under low cycle loading. The FEM can simulate the opening and closing of the contact surfaces among slabs, beams and columns, as well as plastic damage mechanism. Hysteresis curves of the PPEFF joint under every step of low cycle loading from the finite element analysis are compared with those from a previous PPEFF joint experiment, showing good agreement. The effects of slab, post-tensioned strands and energy dissipation rebars on the seismic performance of PPEFF joints are further analyzed in this paper. Based on the analysis, some suggestions for seismic design are given.

Based on the principle of fluorescence resonance energy transfer (FRET), a simple ratiometric fluorescent aptasensor for convenient detection of ochratoxin A (OTA), a Group IIB carcinogen secreted by some fungi, was established. Initially, the anti-OTA aptamer with a quadruplex structure was flanked with FAM and BHQ1, and its partially complementary DNA (cDNA) was tagged with Cy3. In the absence of OTA, this aptamer hybridized with the cDNA strand forming a DNA duplex structure, in which BHQ1 was adjacent to Cy3 and distant from FAM. Due to the FRET principle, the fluorescence intensity emitted by Cy3 (FCy3) was quenched by BHQ1, and the fluorescence intensity emitted by FAM (FFAM) recovered. In the presence of OTA, the prepared aptamer preferred to bind with OTA instead of cDNA, forming an aptamer-OTA complex structure in which BHQ1 was adjacent to FAM and distant from Cy3. As a result, FFAM was quenched and FCy3 was restored. OTA can be accurately detected via the determination of the FCy3/FFAM ratio value. Under optimal conditions, this ratiometric fluorescent aptasensor offers excellent OTA detection in the range of 0.6 nmol L-1-5 μmol L-1, with a limit of detection (LOD) of 0.3 nmol L-1. This ratiometric aptasensor showed the advantages of easy operation, accuracy and sensitive analysis. Good specificity of this aptasensor was demonstrated. This ratiometric aptasensor could be used for the detection of OTA in real samples, e.g. beer and orange juice, showing its promising application potential.

As the second generation of Chinese polar-orbiting meteorological satellite missions, the Fengyun (FY)-3D satellite provides the latest multi-frequency brightness temperature (TB) of FY-3 series satellites. The microwave radiation imager (MWRI) boarded on FY-3D has similar sensor configuration as Advanced Microwave Scanning Radiometer 2 (AMSR2), and thus the intercalibration of these two sensors can make their TB data more consistent and continuous to facilitate their joint applications. In this study, the FY-3D H-pol and V-pol TB at five frequencies from 10.7 to 89 GHz during 2019 to 2020 were calibrated against AMSR2 TB over land. Two categories of intercalibration methods were compared, including global intercalibration method, i.e., global linear regression, and per-pixel-based intercalibration methods, i.e., per-pixel linear regression joint global linear regression, per-pixel linear regression joint inverse distance interpolation, per-pixel linear regression joint nearest neighbor interpolation, and global per-pixel linear regression. Furthermore, the effects of diverse environmental variables (i.e., land cover and its heterogeneity, climate types, water body fraction, terrain and its complexity, soil texture, and vegetation coverage) on FY-3D calibration accuracy were fully investigated. The results indicate that all five approaches can reduce the bias between FY-3D and AMSR2 TB, and the root-mean-square difference (RMSD) also reduces accordingly. Among them, the global per-pixel linear regression method performs the best with the lowest averaged RMSD of 2.93 K (at ascending overpass) and 2.34 K (at descending overpass), followed by the per-pixel linear regression joint inverse distance interpolation. The global linear regression method performs the worst with the largest RMSD of 4.69 and 3.82 K at ascending and descending overpass, respectively. The RMSD is relatively larger in temperate and polar climate zones, as well as in grasslands and croplands than in other climate and land cover types. The calibration errors generally decrease as the altitude increases, while they increase with the increase in land cover heterogeneity. The water body fraction exerts the greatest impact on the calibration accuracy, and the RMSD reaches 3 K when the water body fraction is greater than 15%. Soil texture, terrain complexity, and vegetation coverage generally have little influence on the calibration accuracy. These findings can provide a good reference for the intercalibration of satellites with similar configuration to generate long-term climate data records.