Microfluidic Immunosensor Platform for Sensitive Detection of Human Epidermal Growth Factor Receptor-2 Based on Enhanced Cathode Electrochemiluminescence of Bimetallic Nanoclusters.

In this work, a microfluidic immunosensor chip was developed by incorporating microfluidic technology with electrochemiluminescence (ECL) for sensitive detection of human epidermal growth factor receptor-2 (HER2). The immunosensor chip can achieve robust reproducibility in mass production by integrating multiple detection units in a series. Notably, nanoscale materials can be better adapted to microfluidic systems, greatly enhancing the accuracy of the immunosensor chip. Ag@Au NCs closed by glutathione (GSH) were introduced in the ECL microfluidic immunosensor system with excellent and stable ECL performance. The synthesized CeO2-Au was applied as a coreaction promoter in the ECL signal amplification system, which made the result of HER2 detection more reliable. In addition, the designed microfluidic immunosensor chip integrated the biosensing system into a microchip, realizing rapid and accurate detection of HER2 by its high throughput and low usage. The developed short peptide ligand NARKFKG (NRK) achieved an effective connection between the antibody and nanocarrier for improving the detection efficiency of the sensor. The immunosensor chip had better storage stability and sensitivity than traditional detection methods, with a wide detection range from 10 fg·mL-1 to 100 ng·mL-1 and a low detection limit (LOD) of 3.29 fg·mL-1. In general, a microfluidic immunosensor platform was successfully constructed, providing a new idea for breast cancer (BC) clinical detection.

Mitigation of myocardial ischemia/reperfusion-induced chronic heart failure via Shexiang Baoxin Pill-mediated regulation of the S1PR1 signaling pathway.

BACKGROUND: Well-defined and effective pharmacological interventions for clinical management of myocardial ischemia/reperfusion (MI/R) injury are currently unavailable. Shexiang Baoxin Pill (SBP), a traditional Chinese medicine Previous research on SBP has been confined to single-target treatments for MI/R injury, lacking a comprehensive examination of various aspects of MI/R injury and a thorough exploration of its underlying mechanisms. PURPOSE: This study aimed to investigate the therapeutic potential of SBP for MI/R injury and its preventive effects on consequent chronic heart failure (CHF). Furthermore, we elucidated the specific mechanisms involved, contributing valuable insights into the potential pharmacological interventions for the clinical treatment of MI/R injury. METHODS: We conducted a comprehensive identification of SBP components using high-performance liquid chromatography. Subsequently, we performed a network pharmacology analysis based on the identification results, elucidating the key genes influenced by SBP. Thereafter, through bioinformatics analysis of the key genes and validation through mRNA and protein assays, we ultimately determined the centralized upstream targets. Lastly, we conducted in vitro experiments using myocardial and endothelial cells to elucidate and validate potential underlying mechanisms. RESULTS: SBP can effectively mitigate cell apoptosis, oxidative stress, and inflammation, as well as promote vascular regeneration following MI/R, resulting in improved cardiac function and reduced CHF risk. Mechanistically, SBP treatment upregulates sphingosine-1-phosphate receptor 1 (S1PR1) expression and activates the S1PR1 signaling pathway, thereby regulating the expression of key molecules, including phosphorylated Protein Kinase B (AKT), phosphorylated signal transducer and activator of transcription 3, epidermal growth factor receptor, vascular endothelial growth factor A, tumor necrosis factor-α, and p53. CONCLUSION: This study elucidated the protective role of SBP in MI/R injury and its potential to reduce the risk of CHF. Furthermore, by integrating downstream effector proteins affected by SBP, this research identified the upstream effector protein S1PR1, enhancing our understanding of the pharmacological characteristics and mechanisms of action of SBP. The significance of this study lies in providing compelling evidence for the use of SBP as a traditional Chinese medicine for MI/R injury and consequent CHF prevention.

FeNi-MIL-88B-based electrochemiluminescence immunosensor for ultra-sensitive detection of CD44 protein via dual-quenching strategy.

BACKGROUND: Cluster of Differentiation 44 (CD44) is considered an important biomarker for various cancers, and achieving highly sensitive detection of CD44 is crucial, which plays a significant role in tumor invasion and metastasis, providing essential information for clinical tumor diagnosis. Commonly used methods for analysis include fluorescence spectroscopy (FL), photoelectrochemical analysis (PEC), electrochemical analysis (EC), and commercial ELISA kits. Although these methods offer high sensitivity, they can be relatively complex to perform experimentally. Electrochemiluminescence (ECL) has gained widespread research attention due to its high sensitivity, ease of operation, effective spatiotemporal control, and close to zero background signal. RESULTS: In this work, a sandwich-type ECL immunosensor for detecting CD44 was constructed using luminol as a luminophore. In this sensing platform, bimetallic MOFs (Pd@FeNi-MIL-88B) loaded with palladium nanoparticles (Pd NPs) were used as a novel enzyme mimic, exhibiting excellent catalytic performance towards the electroreduction of H2O2. The hybrids provided a strong support platform for luminol and antibodies, significantly enhancing the initial ECL signal of luminol. Subsequently, core-shell Au@MnO2 nanocomposites were synthesised by gold nanoparticles (Au NPs) encapsulated in manganese dioxide (MnO2) thin layers, as labels. In the luminol/H2O2 system, Au@MnO2 exhibited strong light absorption in the broad UV-vis spectrum, similar to the black body effect, and the scavenging effect of Mn2+ on O2•-, which achieved the dual-quenching of ECL signal. Under the optimal experimental conditions, the immunosensor demonstrated a detection range of 0.1 pg mL-1 - 100 ng mL-1, with a detection limit of 0.069 pg mL-1. SIGNIFICANCE: Based on Pd@FeNi-MIL-88B nanoenzymes and Au@MnO2 nanocomposites, a dual-quenching sandwich-type ECL immunosensor for the detection of CD44 was constructed. The proposed immunosensor exhibited excellent reproducibility, stability, selectivity, and sensitivity, and provided a valuable analytical strategy and technical platform for the accurate detection of disease biomarkers, and opened up potential application prospects for early clinical treatment.

Self-Assembly-Induced Enhancement of Cathodic Electrochemiluminescence of Copper Nanoclusters for a Split-Type Matrix Metalloproteinase 14 Sensing Platform.

The unique optoelectronic and tunable luminescent characteristics of copper nanoclusters (Cu NCs) make them extremely promising as luminophores. However, the limited luminescence intensity and stability of Cu NCs have restricted their application in the field of electrochemiluminescence (ECL). Herein, a self-assembly-induced enhancement strategy was successfully employed to enhance the cathodic ECL performance of flexible ligand-stabilized Cu NCs. Specifically, Cu NCs form ordered sheetlike structures through intermolecular force. The restriction of ligand torsion in this self-assembled structure leads to a significant improvement in the ECL properties of the Cu NCs. Experimental results demonstrate that the assembled nanoscale Cu NC sheets exhibit an approximately three-fold increase in cathodic ECL emission compared to the dispersed state of Cu NCs. Furthermore, assembled nanoscale Cu NCs sheets were utilized as signal probes in conjunction with a specific short peptide derived from the catalytic structural domain of matrix metalloproteinase 14 (MMP 14) as the identification probe, thereby establishing a split-type ECL sensing platform for the quantification of NMP 14. The investigation has revealed the exceptional performance of assembled nanoscale Cu NCs sheets in ECL analysis, thus positioning them as novel and promising signal probes with significant potential in the field of sensing.

Phosphorus-rich CoP4@N-C nanoarrays for efficient nitrate-to-ammonia electroreduction.

The electrochemical nitrate reduction reaction (NO3-RR) is a novel green method for ammonia synthesis. However, the lack of sufficient catalysts has hindered the development of the NO3-RR. This research develops a transformation of porous CoP@N-C/CC into porous phosphorus-rich CoP4@N-C/CC through high-temperature calcination. Due to its unique phosphating-rich structure, CoP4@N-C/CC exhibits an excellent Faraday efficiency (FE: 92.3%) and NH3 yield (610.2 µmol h-1 cm-2). Such a catalyst with more P-P bonds can provide more active sites, effectively enhancing the adsorption and reaction processes of reactant molecules. In addition, the catalyst has good durability and catalytic stability, which provides a possibility for the future application of electrocatalytic ammonia production.

A sensitive immunosensor via Pd@Au0.85Pd0.15 in situ electrocatalysis generating H2O2 for quenching electrochemiluminescence of Ir(pbi)2(acac)@Ti3C2Tx MXene-PVA.

The establishment of rapid target analysis methods for cytokeratin fragment antigen 21-1 (CYFRA 21-1) is urgently needed. [Ir(pbi)2(acac)] (pbi = 2-(4-bromophenyl)-1-hydrogen -benzimidazole, acac = acetylacetonate) as traditional electrochemiluminescence (ECL) luminophores has been confined due to its non-negligible dark toxicity and poor water solubility leading to poor biocompatibility and electrical conductivity as an organic molecule. Hence, to overcome this limitation, [Ir(pbi)2(acac)] can be effectively loaded on the polyvinyl alcohol hydrogel modified Ti3C2Tx MXene surface (Ir@Ti3C2Tx-PVA) as sensing platform which can emit high ECL signals. Then, a quenching strategy was proposed to fabricate an ECL sandwich immunosensor using H2O2 as quencher molecules which can generated by Pd@Au0.85Pd0.15. Especially, the generation of O2 to H2O2 can be achieved through a two-electron (2e-) reaction pathway by Pd@Au0.85Pd0.15, to overcome the restriction that the H2O2 was virtually impossible to label or immobilize on the non-enzyme nanomaterials. The proposed ECL assay achieves a response to CYFRA 21-1 within the range of 0.1 pg/mL-100 ng/mL, with a detection limit of 8.9 fg/mL (S/N = 3). This work provided a feasible tactic to seek superior-performance ECL luminophore and quencher consequently set up a novel means to makeup ultrasensitive ECL biosensor, which extended the utilization potential of Ir(pbi)2(acac) in ECL assays.

Clustering of HR + /HER2- breast cancer in an Asian cohort is driven by immune phenotypes.

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2- breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.

Strong aggregation-induced electrochemiluminescence of pyrene-coordination metal-organic frameworks coupled with zero-valent iron as novel accelerator for ultrasensitive immunoassay.

Polycyclic aromatic hydrocarbons (PAHs) are excellent alternative luminophores for electrochemiluminescence (ECL) immunoassays. However, they are inevitably limited by the aggregation-caused quenching effect. In this study, aimed at eliminating the aggregation quenching of PAHs, luminescent metal-organic frameworks (MOFs) with 1,3,6,8-tetra(4-carboxybenzene)pyrene (H4TBAPy) as the ligand were exploited as a novel nano-emitter for the construction of ECL immunoassays. The luminophore exhibits efficient aggregation-induced emission enhancement, good acid-base resistance property and unusual ECL reactivity. In addition, the simultaneous use of potassium persulfate and hydrogen peroxide as dual co-reactants resulted in a synergistic enhancement of the cathodic ECL efficiency. The use of magnetic iron-nickel alloys as the multifunctional sensing platform can further enhance the ECL activity, and its enriched zero-valent iron as a co-reactant accelerator effectively drives ECL analytical performance. Profiting from the excellent characteristics, signal-on ECL immunoassays have been constructed. With carcinoembryonic antigen as the model analysis target, a detection limit of 0.63 pg/mL was obtained within the linear range of 1 pg/mL to 50 ng/mL, accompanied by excellent analytical performance. This report opens a new window for the rational design of efficient ECL illuminators, and the proposed ECL immunoassays may find promising applications in the detection of disease markers.

A sensitive, portable, and smartphone-based whole-cell biosensor device for salicylic acid monitoring.

Considerable effort has been invested in developing salicylic acid (SA) biosensors for various application purposes. Here, by engineering the sensing modules and host cell chassis, we have gradually optimized the NahR-Psal/Pr-based SA biosensor, increasing the sensitivity and maximum output by 17.2-fold and 9.4-fold, respectively, and improving the detection limit by 800-fold, from 80 µM to 0.1 µM. A portable SA sensing device was constructed by embedding a gelatin-based hydrogel containing an optimized biosensor into the perforations of tape adhered to glass slide, which allowed good determination of SA in the range of 0.1 µM-10 µM. Then, we developed a customized smartphone App to measure the fluorescence intensity of each perforation and automatically calculate the corresponding SA concentration so that we could detect SA concentrations in real cosmetic samples. We anticipate that this smartphone-based imaging biosensor, with its compact size, higher sensitivity, cost-effectiveness, and easy data transfer, will be useful for long-term monitoring of SA.

Controlled-Release Electrochemiluminescence Biosensor with Strong Self-On Effect by a Multiple Signal Amplification Strategy for Trace Detection of Prostate-Specific Antigen.

The enhancement of sensitivity in biological analysis detection can reduce the probability of false positives of the biosensor. In this work, a novel self-on controlled-release electrochemiluminescence (CRE) biosensor was designed by multiple signal amplification and framework-enhanced stability strategies. As a result, the changes of the ECL signal were enhanced before and after the controlled-release process, achieving sensitive detection of prostate-specific antigen (PSA). Specifically, for one thing, Fe3O4@CeO2-NH2 with two paths for enhancing the generation of coreactant radicals was used as the coreaction accelerator to boost ECL performance. For another, due to the framework stability, zeolitic imidazolate framework-8-NH2 (ZIF-8-NH2) was combined with luminol to make the ECL signal more stable. Based on these strategies, the constructed CRE biosensor showed a strong self-on effect in the presence of PSA and high sensitivity in a series of tests. The detection range and limit of detection (LOD) were 5 fg/mL to 10 ng/mL and 2.8 fg/mL (S/N = 3), respectively, providing a feasible approach for clinical detection of PSA.

Interfacial charge transfer in sheet Ni2P-FePx heterojunction to promote the study of electrocatalytic oxygen evolution.

The substantial expense associated with catalysts significantly hampers the progress of electrolytic water-based hydrogen production technology. There is an urgent need to find non-precious metal catalysts that are both cost-effective and highly efficient. Here, the porous Ni2P-FePx nanomaterials were successfully prepared by hydrothermal method, nickel foam as the base, iron nitrate solution as the caustic agent and iron source, and finally phosphating at low temperature. The obtained porous Ni2P-FePx nanosheets showed excellent catalytic activity under alkaline PH = 14, and an overpotential of merely 241 mV was required to achieve a current density of 50 mA cm-2. The morphology of the nanosheet can still be flawlessly presented on the screen after 50 h of working at high current density.

Prediction of Lymphovascular Space Invision in Endometrial Cancer based on Multi-parameter MRI Radiomics Model.

Objective: To explore the application value of a combined model based on multi-parameter MRI radiomics and clinical features in preoperative prediction of lymphatic vascular space invasion (LVSI) in endometrial carcinoma (EC). METHODS: This retrospective study collected the clinicopathological and imaging data of 218 patients with EC in Yuncheng Central Hospital from March 2018 to May 2022. The patients were randomly divided into training group (n=152) and validation group (n= 66) according to the ratio of 7: 3. Based on the ADC, CE-sag, CE-tra, DWI, T2WI-sag-fs, T2WI-tra sequence images of each patient, the region of interest was manually segmented and the features were extracted. The four-step dimensionality reduction method based on max-relevance and min-redundancy (MRMR) and least absolute shrinkage and selection operator (LASSO) regression was used for feature selection and radiomics model construction. Independent predictors of clinicopathological features were screened by multivariate logistic regression analysis. The imaging model based on ADC, CE-sag, CE-tra, DWI, T2WI-sag-fs, T2WI-tra single sequence and combined sequence and the fusion model with clinicopathological features were constructed, and the nomogram was made. ROC curve, correction curve and decision analysis curve were used to evaluate the efficacy and clinical benefits of the nomogram. RESULTS: There was no significant difference in general clinical data between the training and validation groups (P > 0.05). After screening the extracted features, 16 radiomics features were obtained, which were all related to LVSI in EC patients (P < 0.05). The area under the ROC curve (AUC) of the six independent sequence radiomics models in the training group was 0.807, 0.794, 0.826, 0.794, 0.828, 0.824, respectively. The AUC corresponding to the radiomics model constructed by the combined sequence was 0.884, and the diagnostic efficiency was the best, which was verified in the validation group. The AUC of the nomogram constructed by the combined radiomics model and age maximum tumor diameter(MTD), lymph node enlargement (LNE) in the training group and the validation group were 0.914 and 0.912, respectively. The correction curve shows that the nomogram has good correction performance. The decision curve suggests that taking radiomics nomogram to predict LVSI net benefit when the risk threshold is > 10% is better than considering all patients as LVSI+ or LVSI-. CONCLUSION: The combined model based on multi-parametric MRI radiomics features and clinical features has good predictive value for LVSI status in EC patients.

A Co-Reactive Immunosensor Based on Ti3C2Tx MXene@TiO2-MoS2 Hybrids Promoting luminol@Au@Ni-Co NCs Electrochemiluminescence for CYFRA 21-1 Detection.

The construction of assays is capable of accurately detecting cytokeratin-19 (CYFRA 21-1), which is critical for the rapid diagnosis of nonsmall cell lung cancer. In this work, a novel electrochemiluminescence (ECL) immunosensor based on the co-reaction promotion of luminol@Au@Ni-Co nanocages (NCs) as ECL probe by Ti3C2Tx MXene@TiO2-MoS2 hybrids as co-reaction accelerator was proposed to detect CYFRA 21-1. Ni-Co NCs, as a derivative of Prussian blue analogs, can be loaded with large quantities of Au NPs, luminol, and CYFRA 21-1 secondary antibodies due to their high specific surface area. To further improve the sensitivity of the developed ECL immunosensor, Ti3C2Tx MXene@TiO2-MoS2 hybrids were prepared by in situ growth of TiO2 nanosheets on highly conductive Ti3C2Tx MXene, and MoS2 was homogeneously grown on Ti3C2Tx MXene@TiO2 surfaces by the hydrothermal method. Ti3C2Tx MXene@TiO2-MoS2 hybrids possess excellent catalytic performance on the electro-redox of H2O2 generating more O2·- and obtaining optimal ECL intensity of the luminol/H2O2 system. Under the appropriate experimental conditions, the quantitative detection range of CYFRA 21-1 was from 0.1 pg mL-1 to 100 ng mL-1, and the limit of detection (LOD) was 0.046 pg mL-1. The present sensor has a lower LOD with a wider linear range, which provides a new analytical assay for the early diagnosis of small-cell-type lung cancer labels.

Ultrasensitive Detection of SARS-CoV-2 Nucleocapsid Protein Based on Porphyrin-Based Metal-Organic Gels with Highly Efficient Electrochemiluminescence at Low Potential.

Metal-organic gels (MOGs) are a new type of intelligent soft material, which are bridged by metal ions and organic ligands through noncovalent interactions. In this paper, we prepared highly stable P-MOGs, using the classical organic electrochemiluminescence (ECL) luminescence meso-tetra(4-carboxyphenyl)porphine as the organic ligand and Fe3+ as the metal ion. Surprisingly, P-MOGs can stably output ECL signals at a low potential. We introduced P-MOGs into the ECL resonance energy transfer strategy (ECL-RET) and constructed a quenched ECL immunosensor for the detection of the SARS-CoV-2 nucleocapsid protein (SARS-CoV-2-N). In the ECL-RET system, P-MOGs were used as energy donors, and Au@Cu2O@Fe3O4 were selected as energy acceptors. The ultraviolet-visible spectrum of Au@Cu2O@Fe3O4 partially overlaps with the ECL spectrum of P-MOGs, which can effectively touch off the ECL-RET behavior between the donors and receptors. Under the ideal experimental situation, the linear detection range of the SARS-CoV-2-N concentration was 10 fg/mL to 100 ng/mL, and the limit of detection was 1.5 fg/mL. This work has broad application prospects for porphyrin-MOGs in ECL sensing.

Ultrasensitive Electrochemiluminescence Biosensor Based on Efficient Signal Amplification of Copper Nanoclusters Induced by CaMnO3 for CD44 Trace Detection.

Metal nanoclusters (Me NCs) have become a research hotspot in the field of electrochemiluminescence (ECL) sensing analysis. This is primarily attributed to their excellent luminescent properties and biocompatibility along with their easy synthesis and labeling characteristics. At present, the application of Me NCs in ECL mainly focuses on precious metals, whose high cost, to some extent, limits their widespread application. In this work, Cu NCs with cathode ECL emissions in persulfate (S2O82-) were prepared as signal probes using glutathione as ligands, which exhibited stable luminescence signals and high ECL efficiency. At the same time, CaMnO3 was introduced as a co-reaction promoter to increase the ECL responses of Cu NCs, thereby further expanding their application potential in biochemical analysis. Specifically, the reversible conversion of Mn3+/Mn4+ greatly promoted the generation of sulfate radicals (SO4•-), providing a guarantee for improving the luminescence signals of Cu NCs. Furthermore, a short peptide (NARKFYKGC) was introduced to enable the fixation of antibodies to specific targets, preventing the occupancy of antigen-binding sites (Fab fragments). Therefore, the sensitivity of the biosensor could be significantly enhanced by releasing additional Fab fragments. Considering the approaches discussed above, the constructed biosensor could achieve sensitive detection of CD44 over a broad range (10 fg/mL-100 ng/mL), with an ultralow detection limit of 3.55 fg/mL (S/N = 3), which had valuable implications for the application of nonprecious Me NCs in biosensing analysis.

Combined MRI-TRUS fusion targeted and systematic biopsy versus systematic biopsy alone for the detection of prostate cancer: protocol for a prospective single-centre trial.

INTRODUCTION: The classic way of diagnosing prostate cancer (PCa) is by conducting the 12-core systematic biopsy (SB). However, it has a low detection rate for clinically significant PCa (csPCa) and can lead to the detection of clinically insignificant PCa (cisPCa). Although MRI-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TB) can effectively improve the detection rate of csPCa, it may still miss some cases. Therefore, we propose using a combination of TB and SB methods to enhance the detection rate of csPCa while minimising the detection rate of cisPCa. METHODS AND ANALYSIS: This study is a prospective, single-centre investigation that aims to assess and compare the detection rate of csPCa using MRI-TRUS fusion TB combined with SB versus TRUS 12-core SB alone. Biopsy-naïve men with suspected PCa will be subjected to multiparametric MRI. Patients with Prostate Imaging Reporting and Data System (V.2.1) score ≥3 will be enrolled in the TB-SB combination group. The sample size is established as 660 participants, considering a 10% drop-out rate. The primary outcome is the detection rate of csPCa in men without prior biopsy using MRI-TRUS fusion TB combined with the standard TRUS-guided 12-core SB method. CsPCa will be defined as International Society of Urological Pathology Grade ≥2. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee at the Shanghai Tenth People's Hospital, an affiliated hospital of Tongji University School of Medicine. The research results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: ChiCTR2000036089.

Magnetic photoelectrochemical sensor array utilizing addressing sensing strategy for simultaneous detection of amyloid-ß 42 and microtubule-associated protein tau.

The accurate diagnosis of diseases can be improved by detecting multiple biomarkers simultaneously. This study presents the development of a magnetic photoelectrochemical (PEC) immunosensor array for the simultaneous detection of amyloid-ß 42 (Aß) and microtubule-associated protein (Tau), which are markers for neurodegenerative disorders. A metal-organic framework (MOF) derivative, Fe2O3@FeS2 magnetic composites with exceptional photoelectric and ferromagnetic properties was synthesized while preserving the original structure and advantages. Thus, the immunoassembly process of the sensor can be carried out in homogeneous solution and recovered by magnetic separation. For simultaneous detection, a chip is divided into multiple independent sensing sites, which have the same preparation and detection environment, allowing for the implementation of a self-calibration method. The sensor array demonstrates considerable detection ranges of 0.01-100 ng mL-1 for Aß and 0.05-100 ng mL-1 for Tau, with low detection limits of 2.1 pg mL-1 for Aß and 7.9 pg mL-1 for Tau. The PEC sensor array proposed in this study exhibits exceptional stability, selectivity, and reproducibility, providing a new method for detecting multiple markers.

BASALT refines binning from metagenomic data and increases resolution of genome-resolved metagenomic analysis.

Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.

The FBXW7-binding sites on FAM83D are potential targets for cancer therapy.

Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

Confinement-enhanced electrochemiluminescence by Ru(dcbpy)32+-functionalized γ-CD-MOF@COF-LZU1 porous hybrid material as micro-reactor for CYFRA 21-1 detection.

The improvement of electrochemiluminescence (ECL) performance relies on the electron transfer efficiency between luminophore and coreactant. An ultrasensitive ECL micro-reactor with confinement-enhanced performance was prepared by using the covalent organic framework-LZU1-functionalized metal-organic framework (MOF@COF-LZU1) as a platform to assemble enormous N,N-dibutyl-2-hydroxyethylamine (DBAE) and tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) [Ru(dcbpy)32+] into its pore channels. Compared to individual substances of γ-CD-MOF and COF-LZU1, the synergistic effects can conduce to the enhancement of the intensity, durability and sensitivity of the micro-reactor. Besides, COF-LZU1 can provide a mild environment to accommodate a certain amount of DBAE by concentrating them from the aqueous solution into its hydrophobic cavities and boost the oxidation efficiency of DBAE to generate more DBAE●+ and profited the survival of DBAE●, leading to an improved reaction efficiency with the Ru(dcbpy)32+ intermediate. Thanks to the confinement-enhanced strategy, engineered as high-functioning luminescent materials, Ru@γ-CD-MOF@COF-LZU1 micro-reactors decorated with Au NPs can facilitate electron transfer and capture primary antibodies (Ab1). Moreover, Au-Pd-Pt noble metal aerogels (NMAs) functionalized MoS2 NFs (Au-Pd-Pt NMAs@MoS2 NFs) were chosen as base material due to its large specific surface areas, high porosity, and excellent electrical conductivity. Based on above merits, the sensor demonstrated a sensitive response to CYFRA 21-1 detection in a linear concentration gradient from 10 fg/mL to 50 ng/mL with a detection limit of 0.0055 pg/mL (S/N = 3). The COF-LZU1 decorated ECL micro-reactors were constructed based on the signal amplification strategies to realize accurate CYFRA 21-1 detection.