Electrochemical Biosensing Platform Based on Toehold-Mediated Strand Displacement Reaction and DSN Enzyme-Assisted Amplification for Two-Target Detection.

Simultaneous detection of multiple targets is of great significance for accurate disease diagnosis. Herein, based on duplex-specific nuclease (DSN) assisted signal amplification and the toehold-mediated strand displacement reaction (TSDR), we constructed an electrochemical biosensor with high sensitivity and high specificity for dual-target detection. MiRNA-141 and miRNA-133a were used as the targets, and ferrocene (Fc) and methylene blue (MB) with significant peak potential differentiation were used as the electrochemical signal probes. The elaborately designed hairpin probe H1, which was fixed on the electrode surface, could be hybridized with the target miRNA-141 to perform signal amplification by the DSN-assisted enzyme cleavage cycle; thus, miRNA-141 could be detected by Fc signal changes at 0.41 V. The hairpin H1 can also combine with the MB-labeled signal probe (SP) output from miRNA-133a-induced TSDR, and the detection of miRNA-133a can be realized according to the response signal generated by MB at -0.26 V. The two sensing lines are independent of each other, and there is no mutual interference in the detection process. Therefore, two independent detection lines could be connected in series, and the simultaneous detection of two targets can be achieved on a single electrode. This novel detection strategy provides a new way to simultaneously detect different biomarkers.

High Muscle Expression of IGF2BP1 Gene Promotes Proliferation and Differentiation of Chicken Primary Myoblasts: Results of Transcriptome Analysis.

Muscle development is a multifaceted process influenced by numerous genes and regulatory networks. Currently, the regulatory network of chicken muscle development remains incompletely elucidated, and its molecular genetic mechanisms require further investigation. The Longsheng-Feng chicken, one of the elite local breeds in Guangxi, serves as an excellent resource for the selection and breeding of high-quality broiler chickens. In this study, we conducted transcriptome sequencing of the pectoral muscles of Longsheng-Feng chickens and AA broiler chickens with different growth rates. Through comprehensive bioinformatics analysis, we identified differentially expressed genes that affect muscle growth and showed that IGF2BP1 is a key participant in chicken muscle development. Subsequently, we employed QRT-PCR, EdU staining, and flow cytometry to further investigate the role of IGF2BP1 in the proliferation and differentiation of chicken myogenic cells. We identified 1143 differentially expressed genes, among which IGF2BP1 is intimately related to the muscle development process and is highly expressed in muscle tissues. Overexpression of IGF2BP1 significantly promotes the proliferation and differentiation of chicken primary myoblasts, while knockdown of IGF2BP1 significantly inhibits these processes. In summary, these results provide valuable preliminary insights into the regulatory roles of IGF2BP1 in chicken growth and development.

Identification of genes associated with sperm storage capacity in hens at different times after insemination by RNA-seq and Ribo-seq.

BACKGROUND: Sperm storage capacity (SSC) determines the duration of fertility in hens and is an important reproduction trait that cannot be ignored in production. Currently, the genetic mechanism of SSC is still unclear in hens. Therefore, to explore the genetic basis of SSC, we analyzed the uterus-vagina junction (UVJ) of hens with different SSC at different times after insemination by RNA-seq and Ribo-seq. RESULTS: Our results showed that 589, 596, and 527 differentially expressed genes (DEGs), 730, 783, and 324 differentially translated genes (DTGs), and 804, 625, and 467 differential translation efficiency genes (DTEGs) were detected on the 5th, 10th, and 15th days after insemination, respectively. In transcription levels, we found that the differences of SSC at different times after insemination were mainly reflected in the transmission of information between cells, the composition of intercellular adhesion complexes, the regulation of ion channels, the regulation of cellular physiological activities, the composition of cells, and the composition of cell membranes. In translation efficiency (TE) levels, the differences of SSC were mainly related to the physiological and metabolic activities in the cell, the composition of the organelle membrane, the physiological activities of oxidation, cell components, and cell growth processes. According to pathway analysis, SSC was related to neuroactive ligand-receptor interaction, histidine metabolism, and PPAR signaling pathway at the transcriptional level and glutathione metabolism, oxidative phosphorylation, calcium signaling pathway, cell adhesion molecules, galactose metabolism, and Wnt signaling pathway at the TE level. We screened candidate genes affecting SSC at transcriptional levels (COL4A4, MUC6, MCHR2, TACR1, AVPR1A, COL1A1, HK2, RB1, VIPR2, HMGCS2) and TE levels(COL4A4, MUC6, CYCS, NDUFA13, CYTB, RRM2, CAMK4, HRH2, LCT, GCK, GALT). Among them, COL4A4 and MUC6 were the key candidate genes differing in transcription, translation, and translation efficiency. CONCLUSIONS: Our study used the combined analysis of RNA-seq and Ribo-seq for the first time to investigate the SSC and reveal the physiological processes associated with SSC. The key candidate genes affecting SSC were screened, and the theoretical basis was provided for the analysis of the molecular regulation mechanism of SSC.

The sperm storage capacity in hens was correlated with the morphological differences of the oviduct and uterus-vagina junction.

The fertilization rate is an important index to evaluate the reproductive capacity of hens, which is mainly affected by semen quality, timing of artificial insemination (AI), and the ability to store sperm. A high sperm storage (SS) capacity can extend the interval, reduce the frequency, and decrease the labor costs of AI. However, relatively few studies have investigated the SS capacity of hens. Therefore, the aims of the present study were to identify factors influencing the SS capacity of Guangxi partridge chickens and to explore the impact of the sperm count in different sections of the oviduct and sperm storage tubules (SSTs), in addition to the number and surface area of SSTs on SS capacity at different time points after AI. We found that SS capacity was positively correlated to the egg production rate (P < 0.01) and body length (P < 0.05). On post-AI days 5, 10, and 15, the sperm count was higher in uterus-vagina junction (UVJ) than the magnum, isthmus, and infundibulum (P < 0.01), but gradually decreased over time. Also, the duration of SS and the sperm count of the UVJ was greater in the high SS group than the low SS group (P < 0.05). Histopathological analysis of the UVJ showed that the number and surface area of the SSTs (P < 0.01), as well as the proportion of SSTs containing sperm, were greater in the high SS group at all time points post AI (P < 0.01), while the proportion of SSTs containing sperm gradually decreased over time. Collectively, these results highlight the potential for selective breeding of SS capacity and show that SS capacity is related to laying performance and body length of Guangxi partridge hens. In addition, SS capacity was positively correlated to the surface area of SSTs and the proportion containing sperm. A greater sperm count stored in the UVJ was correlated to more sperm transported to the infundibulum and subsequent greater SS capacity of hens.

Primary hepatic neuroendocrine neoplasms: imaging characteristics and misdiagnosis analysis.

Objective: To analyze the CT and MR features of Primary hepatic neuroendocrine neoplasms (PHNENs) in order to enhance the diagnostic accuracy of this disease. Methods: A retrospective analysis was conducted on patients diagnosed with hepatic neuroendocrine neoplasms, excluding other sites of origin through general examination and postoperative follow-up. The CT and MR signs were analyzed according to the 2018 version of Liver Imaging Reporting and Data System (LI-RADS), along with causes of misdiagnosis. Results: Twelve patients, including 6 males and 6 females, were enrolled in this study. There was no significant increase in liver tumor markers among all cases. Most masses were multiple (9/12), exhibiting low attenuation on pre-contrast CT scans, T1-hypointense signal, T2-hyperintense signal, and restricted diffusion. The majority of these masses (7/10) demonstrated similar rim arterial phase hyper-enhancement as well as peripheral "washout" during venous portal phase and delayed phase imaging. Three cases had incomplete capsules while one case had a complete capsule. Cyst/necrosis was observed in 7 out of all cases following administration of contrast agent, with 5 mainly distributed in the periphery. All masses lacked fat, calcification, vascular or bile duct tumor thrombus formation. Conclusion: The imaging findings associated with PHNENs possess certain specificity, often presenting as multiple masses within the liver accompanied by peripheral cyst/necrosis, similar rim arterial phase hyper-enhancement during venous portal phase and delayed phase imaging.

DNA Framework-Programmed Nanoscale Enzyme Assemblies.

Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined enzyme activity in vitro remains unexplored, primarily owing to limitations in precisely controlling the spatial topological configuration. Herein, we introduce a nanoscale 3D enzyme assembly using a tetrahedral DNA framework (TDF), enabling the replication of spatial topological configuration and maintenance of an identical edge-to-edge distance akin to natural enzymes. Our results demonstrate that 3D nanoscale enzyme assemblies in both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) and three-enzyme systems (amylglucosidase (AGO)/GOx/HRP) lead to enhanced cascade catalytic activity compared to the low-dimensional structure, resulting in ∼5.9- and ∼7.7-fold enhancements over homogeneous diffusional mixtures of free enzymes, respectively. Furthermore, we demonstrate the enzyme assemblies for the detection of the metabolism biomarkers creatinine and creatine, achieving a low limit of detection, high sensitivity, and broad detection range.

Renal Lesions with Low-level Enhancement on Contrast-enhanced CT Promotes Early Detection of Drug-induced Kidney Injury in Patients Administered Anticancer Drugs.

BACKGROUND: Some patients with cancer-administered anti-cancer drugs may develop renal lesions with low-level enhancement on follow-up abdominal computed tomography (CT). OBJECTIVE: To explore the clinical significance of renal lesions with low-level enhancement on CT after exposure to anti-cancer drugs. METHODS: Medical records of patients with cancer who developed renal lesions on CT after exposure to anti-cancer drugs were retrospectively reviewed. Renal lesions were scored according to the extent of involvement, CT attenuation values of lesions and normal parenchyma were measured on precontrast CT and three phases of contrast-enhanced CT, and changes in serum creatinine (SCr) from one week before exposure to drugs to one week before and after the appearance of renal lesions were recorded. RESULTS: This study included 54 patients (86 lesions). Lesions were slightly lower density on pre-contrast CT, and less enhancing than normal renal parenchyma, especially in the delayed phase. Lesions were wedge-shaped, and involved the renal pyramid and associated renal cortex, as well as, were single or multiple, and occurred in the unilateral or bilateral kidneys. There were patchy and cord-like shadows of increased density in adjacent perirenal adipose tissue. During follow-up, lesions disappeared in 15 patients and persisted in 39 patients without significant progression. There were significant differences in renal lesions and normal renal parenchyma CT attenuation values in each phase of contrast-enhanced CT. Change in SCr level was significantly positively correlated with lesion score. CONCLUSION: Renal lesions with low-level enhancement on CT suggest early drug-induced kidney injury. These findings will inform clinical decision-making.

DNA Framework-Engineered Assembly of Cyanine Dyes for Structural Identification of Nucleic Acids.

DNA nanostructures serve as precise templates for organizing organic dyes, enabling the creation of programmable artificial photonic systems with efficient light-harvesting and energy transfer capabilities. However, regulating the organization of organic dyes on DNA frameworks remains a great challenge. In this study, we investigated the factors influencing the self-assembly behavior of cyanine dye K21 on DNA frameworks. We observed that K21 exhibited diverse assembly modes, including monomers, H-aggregates, J-aggregates, and excimers, when combined with DNA frameworks. By manipulating conditions such as the ion concentration, dye concentration, and structure of DNA frameworks, we successfully achieved precise control over the assembly modes of K21. Leveraging K21's microenvironment-sensitive fluorescence properties on DNA nanostructures, we successfully discriminated between the chirality and topology structures of physiologically relevant G-quadruplexes. This study provides valuable insights into the factors influencing the dynamic assembly behavior of organic dyes on DNA framework nanostructures, offering new perspectives for constructing functional supramolecular aggregates and identifying DNA secondary structures.

Intravenous administration of IL-12 encoding self-replicating RNA-lipid nanoparticle complex leads to safe and effective antitumor responses.

Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Therapies that can synergistically modulate innate immunity and stimulate adaptive anti-tumor responses are of great interest for cancer immunotherapy. Here we investigated the lipid nanoparticle-encapsulated self-replicating RNA (srRNA) encoding IL-12 (referred to as JCXH-211) for the treatment of cancers. Both local (intratumoral) and systemic (intravenous) administration of JCXH-211 in tumor-bearing mice induced a high-level expression of IL-12 in tumor tissues, leading to modulation of tumor microenvironment and systemic activation of antitumor immunity. Particularly, JCXH-211 can inhibit the tumor-infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). When combined with anti-PD1 antibody, it was able to enhance the recruitment of T cells and NK cells into tumors. In multiple mouse solid tumor models, intravenous injection of JCXH-211 not only eradicated large preestablished tumors, but also induced protective immune memory that prevented the growth of rechallenged tumors. Finally, intravenous injection of JCXH-211 did not cause noticeable systemic toxicity in tumor-bearing mice and non-human primates. Thus, our study demonstrated the feasibility of intravenous administration of JCXH-211 for the treatment of advanced cancers.

Enhanced Detection of Novel Low-Frequency Gene Fusions via High-Yield Ligation and Multiplexed Enrichment Sequencing.

Panel-based methods are commonly employed for the analysis of novel gene fusions in precision diagnostics and new drug development in cancer. However, these methods are constrained by limitations in ligation yield and the enrichment of novel gene fusions with low variant allele frequencies. In this study, we conducted a pioneering investigation into the stability of double-stranded adapter DNA, resulting in improved ligation yield and enhanced conversion efficiency. Additionally, we implemented blocker displacement amplification, achieving a remarkable 7-fold enrichment of novel gene fusions. Leveraging the pre-enrichment achieved with this approach, we successfully applied it to Nanopore sequencing, enabling ultra-fast analysis of novel gene fusions within one hour with high sensitivity. This method offers a robust and remarkably sensitive mean of analyzing novel gene fusions, promising the discovery of pivotal biomarkers that can significantly improve cancer diagnostics and the development of new therapeutic strategies.

Rice-Magnaporthe oryzae interactions in resistant and susceptible rice cultivars under panicle blast infection based on defense-related enzyme activities and metabolomics.

Rice blast, caused by rice blast fungus (Magnaporthe oryzae), is a global threat to food security, with up to 50% yield losses. Panicle blast is a severe form of rice blast, and disease responses vary between cultivars with different genotypes. Reactive oxygen species (ROS)-mediated signaling reactions and the phenylpropanoid pathway are important defense mechanisms involved in recognizing and resisting against fungal infection. To understand rice-M. oryzae interactions in resistant and susceptible cultivars, we determined dynamic changes in the activities of five defense-related enzymes in resistant cultivar jingsui 18 and susceptible cultivar jinyuan 899 infected with M. oryzae from 4 to 25 days after infection. We then performed untargeted metabolomics analyses to profile the metabolomes of the cultivars under infected and non-infected conditions. Dynamic changes in the activities of five defense-related enzymes were closely related to panicle blast resistance in rice. Metabolome data analysis identified 634 differentially accumulated metabolites (DAMs) between resistant and susceptible cultivars following infection, potentially explaining differences in disease response between varieties. The most enriched DAMs were associated with lipids and lipid-like molecules, phenylpropanoids and polyketides, organoheterocyclic compounds, organic acids and derivatives, and lignans, neolignans, and related compounds. Multiple metabolic pathways are involved in resistance to panicle blast in rice, including biosynthesis of other secondary metabolites, amino acid metabolism, lipid metabolism, phenylpropanoid biosynthesis, arachidonic acid metabolism, arginine biosynthesis, tyrosine metabolism, tryptophan metabolism, tyrosine and tryptophan biosynthesis, lysine biosynthesis, and oxidative phosphorylation.

Encapsulation of Enzymes into Hydrophilic and Biocompatible Metal Azolate Framework: Improved Functions of Biocatalyst in Cascade Reactions and its Sensing Applications.

Multiple enzyme-triggered cascade biocatalytic reactions are vital in vivo or vitro, considering the basic biofunction preservation in living organisms and signals transduction for biosensing platforms. Encapsulation of such enzymes into carrier endows a sheltering effect and can boost catalytic performance, although the selection and preparation of an appropriate carrier is still a concern. Herein, focusing on MAF-7, a category of metal azolate framework (MAF) with superiority against the topologically identical ZIF-8, this enzyme@MAF system can ameliorate the sustainability of encapsulating natural enzymes into carriers. The proposed biocatalyst composite AChE@ChOx@MAF-7/hemin is constructed via one-pot in situ coprecipitation method. Subsequently, MAF-7 is demonstrated to exhibit an excellent capacity of the carrier and protection against external factors in the counterpart of ZIF-8 through encapsulated and free enzymes. In addition, detections for specific substrates or inhibitors with favorable sensitivity are accomplished, indicating that the properties above expectation of different aspects of the established platform are successfully realized. This biofunctional composite based on MAF-7 can definitely provide a potential approach for optimization of cascade reaction and enzyme encapsulation.

Genome-scale cis-acting catabolite-responsive element editing confers Bacillus pumilus LG3145 plant-beneficial functions.

Rhizosphere dwelling microorganism such as Bacillus spp. are helpful for crop growth. However, these functions are adversely affected by long-term synthetic fertilizer application. We developed a modified CRISPR/Cas9 system using non-specific single-guide RNAs to disrupt the genome-wide cis-acting catabolite-responsive elements (cres) in a wild-type Bacillus pumilus strain, which conferred dual plant-benefit properties. Most of the mutations occurred around imperfectly matched cis-acting elements (cre-like sites) in genes that are mainly involved in carbon and secondary metabolism pathways. The comparative metabolomics and transcriptome results revealed that carbon is likely transferred to some pigments, such as riboflavin, carotenoid, and lycopene, or non-ribosomal peptides, such as siderophore, surfactin, myxochelin, and bacilysin, through the pentose phosphate and amino acid metabolism pathways. Collectively, these findings suggested that the mutation of global cre-like sequences in the genome might alter carbon flow, thereby allowing beneficial biological interactions between the rhizobacteria and plants.

Iron-Doped Polymer Dots with Enhanced Fluorescence and Dual Enzyme Activity for Versatile Bioassays.

Nanozymes with multiple functionalities endow biochemical sensing with more sensitive and efficient analytical performance by widening the sensing modes. Meanwhile, the target-oriented design of multifunctional nanozymes for certain biosensing remains challenging. Herein, a constructive strategy of doping iron into polymer dots (PDs) to achieve nanozymes with excellent oxidase-mimicking and peroxidase-mimicking activity is proposed. Compared with the Fe-free PDs prepared under the same mild condition, the Fe-doped PDs (Fe-PDs) exhibit greatly boosted fluorescence at 500 nm. While applying 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate, the fluorescence of the Fe-PDs can be further quenched by oxTMB due to the inner filter effect (IFE). Inspired by this, a simple but efficient colorimetric and fluorometric dual-mode sensing platform is developed for monitoring the reducing substances ascorbic acid (AA), α-glucosidase (α-Glu), and its inhibitors (AGIs). We believe that such multifunctional enzyme-mimic materials will provoke the exploration of multimode sensing strategy with strong practicality to serve as a versatile tool in biochemical sensing.

A sensitive "off-on" electrochemiluminescence DNA sensor based on signal cascade amplification circuit and distance-dependent energy transfer.

A sensitive "off-on" electrochemiluminescence (ECL) DNA sensor was constructed based on Exo III-assisted cascade amplification system. In the cascade amplification circuit, target DNA and Exo III cutting substrate were designed into an inverted T-shaped binding mode to form a stable DNA junction, thus effectively triggering Exo III digestion cycle. During the biosensor assembly process, ferrocene (Fc) and distance-dependent ECL resonance energy transfer (ECL-RET) and surface plasmon resonance (SPR) effects were introduced to regulate the ECL of semiconductor quantum dots (QDs). Carboxylated ZnCdSe/ZnS QDs were used as ECL signal probes and K2S2O8 was coreactant, and the initial cathodic ECL signal of QDs was efficiently quenched through electron and energy transfer with Fc and ECL-RET with Au NPs, leaving the system in "off" state. After the products of cascade amplification were introduced into the electrode surface, the single-stranded DNA modified with Fc was displaced, and the distance between Au NPs and QDs became farther, resulting in a transition from ECL-RET to SPR, and then a significant ECL signal boost was achieved, turning the system into "on" state. The combination of efficient cascade amplification system and sensitive "off-on" ECL signal change mode enabled the biosensing platform to detect target DNA with high selectivity (able to distinguish single-base mutated DNA) and ultra-high sensitivity (limit of detection was 31.67 aM, S/N = 3), providing a new perspective for designing highly sensitive and programmable ECL biosensors.

Fluorescent assay for acetylcholinesterase activity and inhibitor screening based on lanthanide organic/inorganic hybrid materials.

It is of great significance for the clinical diagnosis of Alzheimer's disease (AD) to achieve the on-site activity evaluation of acetylcholinesterase (AChE), the hydrolase of acetylcholine (ACh). Herein, we have developed a biosensing method endowed with considerable superiority based on the organic-inorganic hybrid composite Eu(DPA)3@Lap with excellent stability and fluorescent properties for this purpose by loading Eu3+ ions and 2,6-dipicolinic acid (DPA) into LAPONITE® (Lap). Through the comprehensive consideration of the specific hydrolysis of acetylthiocholine (ATCh) into thiocholine (TCh) by AChE, the high binding affinity of TCh to copper ion (Cu2+), and the selective fluorescence quenching ability of Cu2+, a simple Eu(DPA)3@Lap-based assay was developed to realize the rapid and convenient evaluation of AChE activity. Owning to the facile signal on-off-on response mode with a clear PET-based sensing mechanism, our assay presents favorable selectivity and sensitivity (LOD of 0.5 mU mL-1). Furthermore, the fluorescent assay was successfully applied for assessing AChE activity in human serum samples and screening potential AChE inhibitors, showing potential for application in the early diagnosis and drug screening of AD, as a new development path of AD therapy.

Comparing the Catalytic Effect of Metals for Energetic Materials: Machine Learning Prediction of Adsorption Energies on Metals.

Energetic materials (EMs) and metals are the important components of solid propellants, and a strong catalysis of metals on EMs could further enhance the combustion performance of solid propellants. Accordingly, the study on the adsorption of EMs such as octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and ammonium dinitramide (ADN) on metals (Ti, Zr, Fe, Ni, Cu, and Al) was carried out by density functional theory (DFT) to reveal the catalytic effect of metals. The deep dissociation of EMs on Ti and Zr represents a stronger interaction and corresponds to the rapid thermal decomposition behavior of the EMs/metal composite in the experiment. It is expected that DFT calculation can be selected instead of experiments to compare the catalytic effect of metals and preliminarily screen out potential high-performance metals. Based on the data set of the calculated adsorption energy, further machine learning (ML) was used to predict the adsorption energy of EMs on metals for a convenient comparison of the catalytic effect of metals, since a quite high adsorption energy value represents a more thorough dissociation. The kernel ridge regression (KRR) method shows the best performance on predicting adsorption energy and helps to choose the metals for efficiently catalyzing ammonium nitrate (AN) and hexanitrohexaazaisowurtzitane (CL-20). Such adsorption computation and ML not only reveal the decomposition mechanism of EMs on metals but also provide a simple underlying method to predict the catalytic effect of metals.

Combination of Ternary Electrochemiluminescence System of BNQDs/AgMOG-K2S2O8 and Electrochemiluminescence Resonance Energy Transfer Strategy for Ultrasensitive Immunoassay of Amyloid-ß Protein.

In this work, based on boron nitride quantum dots (BNQDs) as energy donors and MnO2@MWCNTs-COOH as energy receptors, we designed an efficient electrochemiluminescence resonance energy transfer (ECL-RET) immunosensor for the detection of amyloid-ß (Aß42) protein, a biomarker of Alzheimer's disease (AD). First, the signal amplification of a ternary ECL system composed of BNQDs (as the ECL emitter), K2S2O8 (as the coreactant), and silver metal-organic gels (AgMOG, as the coreaction accelerator) was realized, and PDDA as stabilizer was added, a strong and stable initial ECL signal was obtained. AgMOG could not only support a large amount of BNQDs and Aß42 capture antibody (Ab1) through Ag-N bond but also exhibit excellent ECL catalytic performance and enhance the luminescent intensity of BNQDs@PDDA-K2S2O8 system. In addition, due to the broad absorption spectrum of MnO2@MWCNTs-COOH and the extensive overlap with the ECL emission spectrum of BNQDs, the quenching probe Ab2-MnO2@MWCNTs-COOH could be introduced into the ternary system through a sandwich immune response. On this basis, the signal on-off ECL immunosensor was constructed to achieve the ultrasensitive detection of Aß42 through signal transformation. Under the optimal conditions, the prepared ECL biosensor manifested a wide linear range (10 fg/mL-100 ng/mL) with a detection limit of 2.89 fg/mL and showed excellent stability, selectivity, and repeatability, which provided an effective strategy for the ultrasensitive detection of biomarkers in clinical analysis.

Programmable Atom-Like Nanoparticle Reporters for High-Precision Urinalysis of In Situ Membrane Proteins.

The expression of disease-specific membrane proteins (MPs) is a crucial indicator for evaluating the onset and progression of diseases. Urinalysis of in situ MPs has the potential for point-of-care disease diagnostics, yet remains challenging due to the lack of molecular reporter to transform the expression information of in situ MPs into the measurable urine composition. Herein, a series of tetrahedral DNA frameworks (TDFs) are employed as the cores of programmable atom-like nanoparticles (PANs) to direct the self-assembly of PAN reporters with defined ligand valence and spatial distribution. With the rational spatial organization of ligands, the interaction between PAN reporters and MPs exhibits superior stability on cell-membrane interface under renal tubule-mimic fluid microenvironment, thus enabling high-fidelity conversion of MPs expression level into binding events and reverse assessment of in situ MP levels via measurement of the renal clearance efficiency of PAN reporters. Such PAN reporter-mediated signal transformation mechanism empowers urinalysis of the onset of acute kidney injury at least 6 h earlier than the existing methods with an area under the curve of 100%. This strategy has the potential for urinalysis of a variety of in situ membrane proteins.

Room-Temperature Synthesized Iron/Cobalt Metal-Organic Framework Nanosheets with Highly Efficient Catalytic Activity toward Luminol Chemiluminescence Reaction.

Two-dimensional (2D) iron/cobalt metal-organic framework nanosheets (Fe/Co-MOF NSs) were synthesized via the cooperative self-assembly reaction of Fe3+/Co2+ and terephthalic acid at room temperature. The as-prepared 2D Fe/Co-MOF NSs display superior performance in catalysis of the chemiluminescence (CL) reaction between luminol and H2O2. The CL spectrum, UV-vis absorption spectroscopy, radical scavenger experiments, and electron spin resonance (ESR) spectroscopy are utilized to research the possible CL mechanism of the luminol-H2O2-Fe/Co-MOF NSs system. All results indicate that Fe/Co-MOF NSs present outstanding peroxidase-like activity and could catalyze H2O2 to produce 1O2, O2·-, and ·OH, which could react rapidly with the luminol anion radical and result in strong CL. With the highly efficient CL of the luminol-H2O2-Fe/Co-MOF NSs system, a sensitive sensor for the detection of dopamine (DA) is developed based on the inhibitory effect of DA on the CL intensity. Good linearity over the range of 50-800 nM is achieved with a limit of detection of 20.88 nM (S/N = 3). This research demonstrates that 2D Fe/Co-MOF NSs is a highly effective catalyst for luminol CL reaction and has great application potential in the CL field.